Co-reporter:Heng Liu;Yike Fu;Yangyang Li;Zhaohui Ren;Xiang Li;Gaorong Han
Langmuir September 6, 2016 Volume 32(Issue 35) pp:9083-9090
Publication Date(Web):2017-2-22
DOI:10.1021/acs.langmuir.6b02227
Implantable localized drug delivery systems (LDDSs) with intelligent functionalities have emerged as a powerful chemotherapeutic platform in curing cancer. Developing LDDSs with rationally controlled drug release and real-time monitoring functionalities holds promise for personalized therapeutic protocols but suffers daunting challenges. To overcome such challenges, a series of porous Yb3+/Er3+ codoped CaTiO3 (CTO:Yb,Er) nanofibers, with specifically designed surface functionalization, were synthesized for doxorubicin (DOX) delivery. The content of DOX released could be optically monitored by increase in the intensity ratio of green to red emission (I550/I660) of upconversion photoluminescent nanofibers under 980 nm near-infrared (NIR) excitation owing to the fluorescence resonance energy transfer (FRET) effect between DOX molecules and the nanofibers. More importantly, the 808 nm NIR irradiation enabled markedly accelerated DOX release, confirming representative NIR-triggered drug release properties. In consequence, such CTO:Yb,Er nanofibers presented significantly enhanced in vitro anticancer efficacy under NIR irradiation. This study has thus inspired another promising fibrous LDDS platform with NIR-triggered and optics-monitored DOX releasing for personalized tumor chemotherapy.
Co-reporter:Gopal Abbineni, Sita Modali, Barbara Safiejko-Mroczka, Valery A. Petrenko, and Chuanbin Mao
Molecular Pharmaceutics October 4, 2010 Volume 7(Issue 5) pp:
Publication Date(Web):July 26, 2010
DOI:10.1021/mp100052y
Filamentous phage as a bacteria-specific virus can be conjugated with an anticancer drug and has been proposed to serve as a carrier to deliver drugs to cancer cells for targeted therapy. However, how cell-targeting filamentous phage alone affects cancer cell biology is unclear. Phage libraries provide an inexhaustible reservoir of new ligands against tumor cells and tissues that have potential therapeutic and diagnostic applications in cancer treatment. Some of these identified ligands might stimulate various cell responses. Here we identified new cell internalizing peptides (and the phages with such peptides fused to each of ∼3900 copies of their major coat protein) using landscape phage libraries and for the first time investigated the actin dynamics when selected phages are internalized into the SKBR-3 breast cancer cells. Our results show that phages harboring VSSTQDFP and DGSIPWST peptides could selectively internalize into the SKBR-3 breast cancer cells with high affinity, and also show rapid involvement of membrane ruffling and rearrangements of actin cytoskeleton during the phage entry. The actin dynamics was studied by using live cell and fluorescence imaging. The cell-targeting phages were found to enter breast cancer cells through energy dependent mechanism and phage entry interferes with actin dynamics, resulting in reorganization of actin filaments and increased membrane rufflings in SKBR-3 cells. These results suggest that, when phage enters epithelial cells, it triggers transient changes in the host cell actin cytoskeleton. This study also shows that using multivalent phage libraries considerably increases the repertoire of available cell-internalizing ligands with potential applications in targeted drug delivery, imaging, molecular monitoring and profiling of breast cancer cells.Keywords: breast cancer cells; cell-internalizing peptide; filamentous actin; Landscape phage library;
Co-reporter:Jie Wang, Shuxu Yang, Chenlin Li, Yungen Miao, Liangjun Zhu, Chuanbin Mao, and Mingying Yang
ACS Applied Materials & Interfaces July 12, 2017 Volume 9(Issue 27) pp:22259-22259
Publication Date(Web):June 30, 2017
DOI:10.1021/acsami.7b05664
Bombyx mori (B. mori) silk fibroin and sericin can act as a great candidate in delivering drugs or other bioactive substances. Silica also has a great application in the field of drug delivery. To the best of our knowledge, there has been no report on the design of a nanocomposite made of silk protein and silica for drug delivery. Here, for the first time, we used B. mori silk fibroin (SF) and sericin (SS), self-assembled into nanospheres and nanofibers in situ in the aqueous solution, respectively, as a biotemplate to regulate the nucleation and self-assembly of silica for designing anticancer drug delivery. SF and SS mediated the nucleation and assembly of silica into monodispersed nanospheres (termed Si/SF) and nanofibers (termed Si/SS), respectively. The size and topography of the silica assemblies were dependent on the concentration of SF or SS as well as reaction conditions. Both Si/SF nanospheres and Si/SS nanofibers showed a high loading capability and sustained release profile of an anticancer drug, doxorubicin (DOX), in vitro. Si/SF nanospheres were found to be efficiently internalized in human cervical carcinoma (HeLa) cells and accumulate around the cell nuclei. Si/SS nanofibers could only adhere to the surface of the cancer cells. This indicates that DOX-loaded Si/SF nanospheres and Si/SS nanofibers are more effective in cancer therapy than free DOX. Our results suggest that the self-assembled Si/SF spheres and Si/SS nanofibers are potential effective anticancer drug carriers.Keywords: drug delivery; nanofibers; nanospheres; protein; silica;
Co-reporter:Mingying Yang, Kegan Sunderland, and Chuanbin Mao
Chemical Reviews August 9, 2017 Volume 117(Issue 15) pp:10377-10377
Publication Date(Web):July 19, 2017
DOI:10.1021/acs.chemrev.7b00100
Novel affinity agents with high specificity are needed to make progress in disease diagnosis and therapy. Over the last several years, peptides have been considered to have fundamental benefits over other affinity agents, such as antibodies, due to their fast blood clearance, low immunogenicity, rapid tissue penetration, and reproducible chemical synthesis. These features make peptides ideal affinity agents for applications in disease diagnostics and therapeutics for a wide variety of afflictions. Virus-derived peptide techniques provide a rapid, robust, and high-throughput way to identify organism-targeting peptides with high affinity and selectivity. Here, we will review viral peptide display techniques, how these techniques have been utilized to select new organism-targeting peptides, and their numerous biomedical applications with an emphasis on targeted imaging, diagnosis, and therapeutic techniques. In the future, these virus-derived peptides may be used as common diagnosis and therapeutics tools in local clinics.
Co-reporter:Yajun Shuai;Shuxu Yang;Chenlin Li;Liangjun Zhu;Mingying Yang
Journal of Materials Chemistry B 2017 vol. 5(Issue 21) pp:3945-3954
Publication Date(Web):2017/05/31
DOI:10.1039/C7TB00208D
Silk sericin, a water-soluble glue-like protein, is extensively used as a biomaterial because it is biocompatible, hydrophilic, and biodegradable. In addition, hydroxylapatite-based carriers are functionally efficient for drug or gene delivery due to their biodegradability, biocompatibility, and easy metabolism in vivo. Herein, for the first time, this study used sericin, from a wild silkworm called Antheraea pernyi (A. pernyi), as a template to nucleate hydroxylapatite (HAp) nanoneedles and form porous sericin–HAp nanocomposite microspheres as an anticancer drug carrier. Specifically, A. pernyi sericin (AS) was incubated in 1.5× simulated body fluid to induce the formation of porous AS/HAp microspheres in situ. Doxorubicin (DOX) loading and release assays proved that the microspheres exhibited pH-dependent controlled and sustained release of DOX. In particular, the microspheres can selectively release DOX at a higher rate at the acidic conditions typical for tumor microenvironment than at the physiological conditions typical for normal tissues, which will potentially reduce the side effects of the cancer drugs in normal tissues. Cancer cell toxicity assay, cancer cell imaging, and intracellular DOX distribution assay provided further evidence to support the pH-dependent controlled and sustained release of DOX to cancer cells from the microspheres. Our work has demonstrated a biomimetic strategy for the design and synthesis of silk protein-based drug carriers that can be potentially employed in drug delivery and regenerative medicine.
Co-reporter:Xiu-Xiu Dong, Jin-Yi Yang, Lin Luo, Yi-Feng Zhang, Chuanbin Mao, Yuan-Ming Sun, Hong-Tao Lei, Yu-Dong Shen, Ross C. Beier, Zhen-Lin Xu
Biosensors and Bioelectronics 2017 Volume 98(Volume 98) pp:
Publication Date(Web):15 December 2017
DOI:10.1016/j.bios.2017.07.014
•A portable immunosensor for sensitive detection of histamine was developed.•Prussian blue-chitosan-gold nanoparticles were used as signal amplification materials.•The immunosensor showed a detection limit of 1.25 ng/mL for histamine in fish samples.Histamine (HA) is a biogenic amine that can accumulate to high concentration levels in food as a result of microbial activity and can cause toxic effects in consumers. In this work, a portable electrochemical immunosensor capable of detecting HA with high sensitivity and selectivity was developed. Prussian blue-chitosan-gold nanoparticle (PB-CS-AuNP) nanocomposite films with excellent biocompatibility were synthesized and characterized by scanning electron microscopy and energy dispersive X-ray analysis. The PB-CS-AuNP were coated onto a screen-printed electrode by one-step electrodeposition and used to conjugate the HA ovalbumin conjugate (HA-Ag). HA was determined by a competition between the coating HA-Ag and the HRP labeled HA antibody (HRP-HA-Ab). After careful optimization of assay conditions and Box-Behnken analysis, the developed immunosensor showed a linear range from 0.01 to 100 μg/mL for HA in fish samples. The average recoveries from spiked samples ranged from 97.25% to 105%. The biosensor also showed good specificity, reproducibility, and stability, indicating its potential application in monitoring HA in a simple and low cost manner.
Co-reporter:Yangyang Li;Yike Fu;Zhaohui Ren;Xiang Li;Gaorong Han
Journal of Materials Chemistry B 2017 vol. 5(Issue 36) pp:7504-7511
Publication Date(Web):2017/09/20
DOI:10.1039/C7TB01142C
Great efforts have been devoted to effective delivery of therapeutics into cells for cancer therapy. The exploration of nanoparticle based drug delivery systems (DDSs) faces daunting challenges due to the low efficacy of intracellular delivery. Herein, a localized drug delivery device consisting of photoluminescent mesoporous silica nanoparticles (PLMSNs) and a photothermal fibrous matrix was investigated. Specifically, PLMSNs modified with a pH-sensitive polydopamine (PDA) ‘gatekeeper’ served as a doxorubicin (DOX) carrier and could release DOX once the PLMSNs were taken up by the cancer cells. The PLMSNs were electrostatically assembled on the surface of an electrospun biodegradable poly(ε-caprolactone)/gelatin fibrous mesh incorporated with photothermal carbon nanoparticles (CNPs), leading to an implantable patch used as a localized delivery platform. Compared to free particulate DDSs, this implantable composite patch device was found to significantly enable a superior cell uptake effect and consequently enhance in vitro therapeutic efficacy against tumor cells. Namely, under near infrared irradiation, the photothermal effect of CNPs in the implantable patch weakens the electrostatic interaction between the PLMSNs and the poly(ε-caprolactone)/gelatin/CNP fibrous mesh, resulting in the controlled release of the PLMSNs and subsequent internalization into the tumor cells for more effective cancer cell killing. This implantable therapeutic device may therefore inspire other means of developing localized cancer therapy.
Co-reporter:Binrui Cao, Mingying Yang, and Chuanbin Mao
Accounts of Chemical Research 2016 Volume 49(Issue 6) pp:1111
Publication Date(Web):May 6, 2016
DOI:10.1021/acs.accounts.5b00557
ConspectusFilamentous bacteriophage (phage) is a genetically modifiable supramacromolecule. It can be pictured as a semiflexible nanofiber (∼900 nm long and ∼8 nm wide) made of a DNA core and a protein shell with the former genetically encoding the latter. Although phage bioengineering and phage display techniques were developed before the 1990s, these techniques have not been widely used for chemistry, materials, and biomedical research from the perspective of supramolecular chemistry until recently. Powered by our expertise in displaying a foreign peptide on its surface through engineering phage DNA, we have employed phage to identify target-specific peptides, construct novel organic–inorganic nanohybrids, develop biomaterials for disease treatment, and generate bioanalytical methods for disease diagnosis. Compared with conventional biomimetic chemistry, phage-based supramolecular chemistry represents a new frontier in chemistry, materials science, and medicine.In this Account, we introduce our recent successful efforts in phage-based supramolecular chemistry, by integrating the unique nanofiber-like phage structure and powerful peptide display techniques into the fields of chemistry, materials science, and medicine: (1) successfully synthesized and assembled silica, hydroxyapatite, and gold nanoparticles using phage templates to form novel functional materials; (2) chemically introduced azo units onto the phage to form photoresponsive functional azo-phage nanofibers via a diazotization reaction between aromatic amino groups and the tyrosine residues genetically displayed on phage surfaces; (3) assembled phage into 2D films for studying the effects of both biochemical (the peptide sequences displayed on the phages) and biophysical (the topographies of the phage films) cues on the proliferation and differentiation of mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs) and identified peptides and topographies that can induce their osteogenic differentiation; (4) discovered that phage could induce angiogenesis and osteogenesis for MSC-based vascularized bone regeneration; (5) identified novel breast cancer cell-targeting and MSC-targeting peptides and used them to significantly improve the efficiency of targeted cancer therapy and MSC-based gene delivery, respectively; (6) employed engineered phage as a probe to achieve ultrasensitive detection of biomarkers from serum of human patients for disease diagnosis; and (7) constructed centimeter-scale 3D multilayered phage assemblies with the potential application as scaffolds for bone regeneration and functional device fabrication.Our findings demonstrated that phage is indeed a very powerful supramacromolecule suitable for not only developing novel nanostructures and biomaterials but also advancing important fields in biomedicine, including molecular targeting, cancer diagnosis and treatment, drug and gene delivery, stem cell fate direction, and tissue regeneration. Our successes in exploiting phage in chemistry, materials, and medicine suggest that phage itself is nontoxic at the cell level and can be safely used for detecting biomarkers in vitro. Moreover, although we have demonstrated successful in vivo tissue regeneration induced by phage, we believe future studies are needed to evaluate the in vivo biodistribution and potential risks of the phage-based biomaterials.
Co-reporter:Chengyun Ning, Peng Yu, Ye Zhu, Mengyu Yao, Xiaojing Zhu, Xiaolan Wang, Zefeng Lin, Weiping Li, Shuangying Wang, Guoxin Tan, Yu Zhang, Yingjun Wang and Chuanbin Mao
NPG Asia Materials 2016 8(3) pp:e243
Publication Date(Web):2016-03-01
DOI:10.1038/am.2016.9
Bone has a built-in electric field because of the presence of piezoelectric collagen. To date, only externally applied electric fields have been used to direct cell behavior; however, these fields are not safe or practical for in vivo use. In this work, for the first time, we use a periodic microscale electric field (MEF) built into a titanium implant to induce osteogenesis. Such a MEF is generated by the periodic organization of a junction made of two parallel semiconducting TiO2 zones: anatase and rutile with lower and higher electron densities, respectively. The junctions were formed through anatase–rutile-phase transition in selective areas using laser irradiation on the implants. The in vitro and in vivo studies confirmed that the built-in MEF was an efficient electrical cue for inducing osteogenic differentiation in the absence of osteogenic supplements and promoted bone regeneration around the implants. Our work opens up a new avenue toward bone repair and regeneration using built-in MEF.
Co-reporter:Guoxin Tan, Shuangying Wang, Ye Zhu, Lei Zhou, Peng Yu, Xiaolan Wang, Tianrui He, Junqi Chen, Chuanbin Mao, and Chengyun Ning
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 37) pp:24306
Publication Date(Web):September 7, 2016
DOI:10.1021/acsami.6b07440
Reactive oxygen species (ROS) can be used to kill bacterial cells, and thus the selective generation of ROS from material surfaces is an emerging direction in antibacterial material discovery. We found the polarization of piezoelectric ceramic causes the two sides of the disk to become positively and negatively charged, which translate into cathode and anode surfaces in an aqueous solution. Because of the microelectrolysis of water, ROS are preferentially formed on the cathode surface. Consequently, the bacteria are selectively killed on the cathode surface. However, the cell experiment suggested that the level of ROS is safe for normal mammalian cells.Keywords: antibacterial mechanism; biocompatibility; piezoceramics; potassium sodium niobate; reactive oxygen
Co-reporter:Yan Li, Binrui Cao, Mingying Yang, Ye Zhu, Junghae Suh, and Chuanbin Mao
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 45) pp:30714
Publication Date(Web):November 1, 2016
DOI:10.1021/acsami.6b09708
Ferroelectric materials, such as tetragonal barium titanate (BaTiO3), have been widely used in a variety of areas including bioimaging, biosensing, and high power switching devices. However, conventional methods for the synthesis of tetragonal phase BaTiO3 usually require toxic organic reagents and high temperature treatments, and are thus not environment-friendly and energy-efficient. Here, we took advantage of the phage display technique to develop a novel strategy for the synthesis of BaTiO3 nanowires. We identified a short BaTiO3-binding/nucleating peptide, CRGATPMSC (named RS), from a phage-displayed random peptide library by biopanning technique and then genetically fused the peptide to the major coat protein (pVIII) of filamentous M13 phages to form the pVIII-RS phages. We found that the resultant phages could not only bind with the presynthesized BaTiO3 crystals but also induce the nucleation of uniform tetragonal BaTiO3 nanocrystals at room temperature and without the use of toxic reagents to form one-dimensional polycrystalline BaTiO3 nanowires. This approach enables the green synthesis of BaTiO3 polycrystalline nanowires with potential applications in bioimaging and biosensing fields.Keywords: barium titanate; bioassembly; phage; polycrystalline nanowires; tetragonal structure
Co-reporter:Mei Li;Zheng Ma;Ye Zhu;Hong Xia;Mengyu Yao;Xiao Chu;Xiaolan Wang;Ke Yang;Mingying Yang;Yu Zhang
Advanced Healthcare Materials 2016 Volume 5( Issue 5) pp:557-566
Publication Date(Web):
DOI:10.1002/adhm.201500712
The antibacterial mechanism of the Cu-containing materials has not been fully understood although such understanding is crucial for the sustained clinical use of Cu-containing antibacterial materials such as bone implants. The aim of this study is to investigate the molecular mechanisms by which the Gram-positive Staphylococcus aureus is inactivated through Cu-bearing titanium alloys (Ti6Al4V5Cu). Cu ions released from the alloys are found to contribute to lethal damage of bacteria. They destroy the permeability of the bacterial membranes, resulting in the leakage of reducing sugars and proteins from the cells. They also promote the generation of bacteria-killing reactive oxygen species (ROS). The ROS production is confirmed by several assays including fluorescent staining of intracellular oxidative stress, detection of respiratory chain activity, and measurement of the levels of lipid peroxidation, catalase, and glutathione. Furthermore, the released Cu ions show obvious genetic toxicity by interfering the replication of nuc (species-specific) and 16SrRNA genes, but with no effect on the genome integrity. All of these effects lead to the antibacterial effect of Ti6Al4V5Cu. Collectively, our work reconciles the conflicting antibacterial mechanisms of Cu-bearing metallic materials or nanoparticles reported in the literature and highlights the potential use of Ti6Al4V5Cu alloys in inhibiting bacterial infections.
Co-reporter:Yanyan Huai;Shuai Dong;Ye Zhu;Xin Li;Binrui Cao;Xiang Gao;Mingying Yang;Li Wang
Advanced Healthcare Materials 2016 Volume 5( Issue 7) pp:786-794
Publication Date(Web):
DOI:10.1002/adhm.201500930
Candida albicans (CA) is a kind of fungus that can cause high morbidity and mortality in immunocompromised patients. However, preventing CA infection in these patients is still a daunting challenge. Herein, inspired from the fact that immunization with secreted aspartyl proteinases 2 (Sap2) can prevent the infection, it is proposed to use filamentous phage, a human-safe virus nanofiber specifically infecting bacteria (≈900 nm long and 7 nm wide), to display an epitope peptide of Sap2 (EPS, with a sequence of Val–Lys–Tyr–Thr–Ser) on its side wall and thus serve as a vaccine for preventing CA infection. The engineered virus nanofibers and recombinant Sap2 (rSap2) are then separately used to immunize mice. The humoral and cellular immune responses in the immunized mice are evaluated. Surprisingly, the virus nanofibers significantly induce mice to produce strong immune response as rSap2 and generate antibodies that can bind Sap2 and CA to inhibit the CA infection. Consequently, immunization with the virus nanofibers in mice dramatically increases the survival rate of CA-infected mice. All these results, along with the fact that the virus nanofibers can be mass-produced by infecting bacteria cost-effectively, suggest that virus nanofibers displaying EPS can be a vaccine candidate against fungal infection.
Co-reporter:Yifan Wang, Jianglin Wang, Hang Hao, Mingle Cai, Shiyao Wang, Jun Ma, Yan Li, Chuanbin Mao, and Shengmin Zhang
ACS Nano 2016 Volume 10(Issue 11) pp:9927
Publication Date(Web):October 31, 2016
DOI:10.1021/acsnano.6b03835
Biocompatible tissue-borne crystalline nanoparticles releasing anticancer therapeutic inorganic elements are intriguing therapeutics holding the promise for both tissue repair and cancer therapy. However, how the therapeutic inorganic elements released from the lattice of such nanoparticles induce tumor inhibition remains unclear. Here we use selenium-doped hydroxyapatite nanoparticles (Se-HANs), which could potentially fill the bone defect generated from bone tumor removal while killing residual tumor cells, as an example to study the mechanism by which selenium released from the lattice of Se-HANs induces apoptosis of bone cancer cells in vitro and inhibits the growth of bone tumors in vivo. We found that Se-HANs induced apoptosis of tumor cells by an inherent caspase-dependent apoptosis pathway synergistically orchestrated with the generation of reactive oxygen species. Such mechanism was further validated by in vivo animal evaluation in which Se-HANs tremendously induced tumor apoptosis to inhibit tumor growth while reducing systemic toxicity. Our work proposes a feasible paradigm toward the design of tissue-repairing inorganic nanoparticles that bear therapeutic ions in the lattice and can release them in vivo for inhibiting tumor formation.Keywords: apoptosis; nanoparticles; osteosarcoma; selenium; tumor inhibition
Co-reporter:Xiang Li, Yangyang Li, Xiaoyi Chen, Binbin Li, Bo Gao, Zhaohui Ren, Gaorong Han, and Chuanbin Mao
Langmuir 2016 Volume 32(Issue 13) pp:3226-3233
Publication Date(Web):March 24, 2016
DOI:10.1021/acs.langmuir.6b00290
Bone regeneration and scaffold degradation do not usually follow the same rate, representing a daunting challenge in bone repair. Toward this end, we propose to use an external field such as light (in particular, a tissue-penetrating near-infrared light) to precisely monitor the degradation of the mineralized scaffold (demineralization) and the formation of apatite mineral (mineralization). Herein, CaTiO3:Yb3+,Er3+@bioactive glass (CaTiO3:Yb3+,Er3+@BG) nanofibers with upconversion (UC) photoluminescence (PL) were synthesized. Such nanofibers are biocompatible and can emit green and red light under 980 nm excitation. The UC PL intensity is quenched during the bone-like apatite formation on the surface of the nanofibers in simulated body fluid; more mineral formation on the nanofibers induces more rapid optical quenching of the UC PL. Furthermore, the quenched UC PL can recover back to its original magnitude when the apatite on the nanofibers is degraded. Our work suggests that it is possible to optically monitor the apatite mineralization and demineralization on the surface of nanofibers used in bone repair.
Co-reporter:Mingying Yang, Guanshan Zhou, Yajun Shuai, Jie Wang, Liangjun Zhu and Chuanbin Mao
Journal of Materials Chemistry A 2015 vol. 3(Issue 12) pp:2455-2462
Publication Date(Web):17 Feb 2015
DOI:10.1039/C4TB01944J
Bone biomineralization is a well-regulated protein-mediated process where hydroxylapatite (HAP) crystals are nucleated with preferred orientation within the self-assembled protein matrix. Mimicking this process is a promising approach to the production of bone-like protein/mineral nanocomposites for bone repair and regeneration. Towards the goal of fabricating such nanocomposites from sericin, a protein spun by Bombyx mori (B. mori) silkworm, and bone mineral HAP, for the first time we investigated the chemical mechanism underpinning the synergistic processes of the conformational change/self-assembly of B. mori sericin (BS) as well as the nucleation of HAP on the resultant self-assembled BS matrix. We found that BS, rich in anionic amino acid residues, could bind Ca2+ ions from the HAP precursor solution through electrostatic attraction. The Ca2+ binding drove the conformational change of BS from random coils into β-sheets and its concomitant self-assembly into the interconnected nanofibrous network-like protein matrix, which initiated the nucleation and growth of HAP crystals. HAP crystals directed by the resultant self-assembled BS matrix grew preferentially along their crystallographic c-axis, leading to the formation of HAP nano-needles. The HAP nano-needles in the self-assembled BS matrix were subsequently aggregated into globules, probably driven by the hydrogen bonding between CO groups of BS and O–H groups of HAP nano-needles. The present work sheds light on the chemical mechanisms of BS self-assembly and the controlled mineralization directed by the self-assembled matrix. We also found that the resultant nanocomposites could promote the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. Thus our work also generates a biomimetic approach to bone-like silk protein/mineral nanocomposite scaffolds that can find potential applications in bone repair and regeneration.
Co-reporter:Xiang Li, Qiuhong Zhang, Zeeshan Ahmad, Jie Huang, Zhaohui Ren, Wenjian Weng, Gaorong Han and Chuanbin Mao
Journal of Materials Chemistry A 2015 vol. 3(Issue 37) pp:7449-7456
Publication Date(Web):28 Aug 2015
DOI:10.1039/C5TB01158B
750–850 nm (NIR I) and 1000–1400 nm (NIR II) in the near infrared (NIR) spectra are two windows of optical transparency for biological tissues with the latter capable of penetrating tissue deeper. Monitoring drug release from the drug carrier is still a daunting challenge in the field of nanomedicine. To overcome such a challenge, we propose to use porous Nd3+-doped CaTiO3 nanofibers, which can be excited by NIR I to emit NIR II light, to carry drugs to test the concept of monitoring drug release from the nanofibers by detecting the NIR II emission intensity. Towards this end, we first used electrospinning to prepare porous Nd3+-doped CaTiO3 nanofibers by adding micelle-forming surfactant Pluronic F127, followed by annealing to remove the organic component. After a model drug, ibuprofen, was loaded into the porous nanofibers, the drug release from the nanofibers into the phosphate buffered saline (PBS) solution was monitored by detecting the NIR II emission from the nanofibers. We found that the release of the drug molecules from the nanofibers into the PBS solution triggers the quenching of NIR II emission by the hydroxyl groups in the surrounding media. Consequently, more drug release corresponded to more reduction in the intensity of the NIR II emission, allowing us to monitor the drug release by simply detecting the intensity of NIR II from the nanofibers. In addition, we demonstrated that tuning the amount of micelle-forming surfactant Pluronic F127 enabled us to tune the porosity of the nanofibers and thus the drug release kinetics. This study suggests that Nd3+ doped CaTiO3 nanostructures can serve as a promising drug delivery platform with the potential to monitor drug release kinetics by detecting the tissue-penetrating NIR emission.
Co-reporter:Guanping He, Yuanhao Wu, Yu Zhang, Ye Zhu, Yang Liu, Nan Li, Mei Li, Guan Zheng, Baohua He, Qingshui Yin, Yufeng Zheng and Chuanbin Mao
Journal of Materials Chemistry A 2015 vol. 3(Issue 32) pp:6676-6689
Publication Date(Web):27 Jul 2015
DOI:10.1039/C5TB01319D
Most of the magnesium (Mg) alloys possess excellent biocompatibility, mechanical properties and biodegradability in orthopedic applications. However, these alloys may suffer from bacterial infections due to their insufficient antibacterial capability. In order to reduce the post-surgical infections, a series of biocompatible Mg–1Ca–0.5Sr–xZn (x = 0, 2, 4, 6) alloys were fabricated with the addition of antibacterial Zn with variable contents and evaluated in terms of their biocompatibility and antibacterial properties. The in vitro corrosion study showed that Mg–1Ca–0.5Sr–6Zn alloys exhibited a higher hydrogen evolution volume after 100 h immersion and resulted in a higher pH value of the immersion solution. Our work indicated that Zn-containing Mg alloys exhibited good biocompatibility with high cell viability. The antibacterial studies reveal that the number of bacteria adhered on all of these Mg alloy samples diminished remarkably compared to the Ti–6Al–4V control group. We also found that the proliferation of the bacteria was inhibited by these Mg alloy extracts. Among the prepared alloys, the Mg–1Ca–0.5Sr–6Zn alloy not only exhibited a strong antibacterial effect, but also promoted the proliferation of MC3T3-E1 osteoblasts, suggesting that it is a promising alloy with both good antibacterial properties and good biocompatibility for use as an orthopedic implant.
Co-reporter:Binrui Cao, Mingying Yang, Lin Wang, Hong Xu, Ye Zhu and Chuanbin Mao
Journal of Materials Chemistry A 2015 vol. 3(Issue 39) pp:7667-7672
Publication Date(Web):03 Sep 2015
DOI:10.1039/C5TB01509J
Synthetic nanoparticles are always terminated with coating molecules, which are often cytotoxic and not desired in biomedicine. Here we propose a novel reaction-dissolution approach to remove the cytotoxic coating molecules. A two-component solution is added to the nanoparticle solution; one component reacts with the coating molecules to form a salt whereas another is a solvent for dissolving and thus removing the salt. As a proof of concept, this work uses a NaOH–ethanol solution to remove the cytotoxic linoleic acid molecules coated on the hydroxyapatite nanorods (HAP-NRs). The removal of the coating molecules not only significantly improves the biocompatibility of HAP-NRs but also enables their oriented attachment into tightly-bound superstructures, which mimic the organized HAP crystals in bone and enamel and can promote the osteogenic differentiation of mesenchymal stem cells. Our reaction-dissolution approach can be extended to the surface “cleaning” of other nanomaterials.
Co-reporter:Qing Zhang, Hua Dong, Yuli Li, Ye Zhu, Lei Zeng, Huichang Gao, Bo Yuan, Xiaofeng Chen, and Chuanbin Mao
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 41) pp:23336
Publication Date(Web):October 12, 2015
DOI:10.1021/acsami.5b07976
Surface topography can affect cell adhesion, morphology, polarity, cytoskeleton organization, and osteogenesis. However, little is known about the effect of topography on the fracture healing in repairing nonunion and large bone defects. Microgrooved topography on the surface of bone implants may promote cell migration into the fracture gap to accelerate fracture healing. To prove this hypothesis, we used an in vitro fracture (wound) healing assay on the microgrooved polycaprolactone substrates to study the effect of microgroove widths and depths on the osteoblast-like cell (MG-63) migration and the subsequent healing. We found that the microgrooved substrates promoted MG-63 cells to migrate collectively into the wound gap, which serves as a fracture model, along the grooves and ridges as compared with the flat substrates. Moreover, the groove widths did not show obvious influence on the wound healing whereas the smaller groove depths tended to favor the collective cell migration and thus subsequent healing. The microgrooved substrates accelerated the wound healing by facilitating the collective cell migration into the wound gaps but not by promoting the cell proliferation. Furthermore, microgrooves were also found to promote the migration of human mesenchymal stem cells (hMSCs) to heal the fracture model. Though osteogenic differentiation of hMSCs was not improved on the microgrooved substrate, collagen I and minerals deposited by hMSCs were organized in a way similar to those in the extracellular matrix of natural bone. These findings suggest the necessity in using microgrooved implants in enhancing fracture healing in bone repair.Keywords: bone; collective cell migration; fracture healing; implants; microgrooved topography
Co-reporter:Meng Wang, Ming Li, Aoyang Yu, Jian Wu, and Chuanbin Mao
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 51) pp:28110
Publication Date(Web):December 17, 2015
DOI:10.1021/acsami.5b09320
The most commonly found fingerprints at crime scenes are latent and, thus, an efficient method for detecting latent fingerprints is very important. However, traditional developing techniques have drawbacks such as low developing sensitivity, high background interference, complicated operation, and high toxicity. To tackle this challenge, we have synthesized two kinds of rare earth fluorescent nanomaterials, including the fluoresce red-emitting YVO4:Eu nanocrystals and green-emitting LaPO4:Ce,Tb nanobelts, and then used them as fluorescent labels for the development of latent fingerprints with high sensitivity, high contrast, high selectivity, high efficiency, and low background interference, on various substrates including noninfiltrating materials, semi-infiltrating materials, and infiltrating materials.Keywords: fingerprint; fluorescent; nanocrystals; nanowires; rare earth
Co-reporter:Yanhua Wang;Hang Hao;Haoming Liu;Yifan Wang;Yan Li;Gaojie Yang;Jun Ma;Shengmin Zhang
Advanced Healthcare Materials 2015 Volume 4( Issue 12) pp:1813-1818
Publication Date(Web):
DOI:10.1002/adhm.201500307
Co-reporter:Chengyun Ning, Xiaolan Wang, Lihua Li, Ye Zhu, Mei Li, Peng Yu, Lei Zhou, Zhengnan Zhou, Junqi Chen, Guoxin Tan, Yu Zhang, Yingjun Wang, and Chuanbin Mao
Chemical Research in Toxicology 2015 Volume 28(Issue 9) pp:1815
Publication Date(Web):August 10, 2015
DOI:10.1021/acs.chemrestox.5b00258
Antibacterial metal ions, such as Ag+, Zn2+ and Cu2+, have been extensively used in medical implants and devices due to their strong broad spectrum of antibacterial activity. However, it is still a controversial issue as to whether they can show the desired antibacterial activity while being toxic to mammalian cells. It is very important to balance their antibacterial effectiveness with minimal damage to mammalian cells. Toward this end, this study is to identify the suitable concentrations of these three ions at which they can effectively kill two types of clinically relevant bacteria (Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli)) but show no obvious cytotoxicity on fibroblasts. Such concentration ranges are found to be 2.5 × 10–7 M–10–6 M, 10–5 M–10–4 M, and 10–5 M–10–4 M for Ag+, Zn2+, and Cu2+, respectively. Investigation of their antibacterial mechanism shows that these three metal ions all show antibacterial property through a mechanism of damaging bacterial cell membranes by the generation of reactive oxygen species but surprisingly preserving the integrity of bacterial genomic DNA. The encouraging results indicate that antibacterial metal ions with controlled concentrations can bring considerable benefits to biomedical applications.
Co-reporter:Jianglin Wang, Gaojie Yang, Yifan Wang, Yinying Du, Haoming Liu, Ye Zhu, Chuanbin Mao, and Shengmin Zhang
Biomacromolecules 2015 Volume 16(Issue 7) pp:
Publication Date(Web):June 16, 2015
DOI:10.1021/acs.biomac.5b00419
Protein-mediated molecular self-assembly has become a powerful strategy to fabricate biomimetic biomaterials with controlled shapes. Here we designed a novel chimeric molecular template made of two proteins, silk fibroin (SF) and albumin (ALB), which serve as a promoter and an inhibitor for hydroxyapatite (HA) formation, respectively, to synthesize HA nanoparticles with controlled shapes. HA nanospheres were produced by the chimeric ALB-SF template, whereas HA nanorods were generated by the SF template alone. The success in controlling the shape of HA nanoparticles allowed us to further study the effect of the shape of HA nanoparticles on the fate of rat mesenchymal stem cells (MSCs). We found that the nanoparticle shape had a crucial impact on the cellular uptake and HA nanospheres were internalized in MSCs at a faster rate. Both HA nanospheres and nanorods showed no significant influence on cell proliferation and migration. However, HA nanospheres significantly promoted the osteoblastic differentiation of MSCs in comparison to HA nanorods. Our work suggests that a chimeric combination of promoter and inhibitor proteins is a promising approach to tuning the shape of nanoparticles. It also sheds new light into the role of the shape of the HA nanoparticles in directing stem cell fate.
Co-reporter:Dong-Dong Wang, Mingying Yang, Ye Zhu, and Chuanbin Mao
Biomacromolecules 2015 Volume 16(Issue 12) pp:
Publication Date(Web):November 20, 2015
DOI:10.1021/acs.biomac.5b01226
Nonviral gene delivery vectors hold great promise for gene therapy due to the safety concerns with viral vectors. However, the application of nonviral vectors is hindered by their low transfection efficiency. Herein, in order to tackle this challenge, we developed a nonviral vector integrating lipids, sleeping beauty transposon system and 8-mer stem cell targeting peptides for safe and efficient gene delivery to hard-to-transfect mesenchymal stem cells (MSCs). The 8-mer MSC-targeting peptides, when synthetically reiterated in three folds and chemically presented on the surface, significantly promoted the resultant lipid-based nanoparticles (LBNs) to deliver VEGF gene into MSCs with a high transfection efficiency (∼52%) and long-lasting gene expression (for longer than 170 h) when compared to nonreiterated peptides. However, the reiterated stem cell targeting peptides do not enable the highly efficient gene transfer to other control cells. This work suggests that the surface presentation of the reiterated stem cell-targeting peptides on the nonviral vectors is a promising method for improving the efficiency of cell-specific nonviral gene transfection in stem cells.
Co-reporter:Huichang Gao, Hua Dong, Xiaodong Cao, Xiaoling Fu, Ye Zhu, Chuanbin Mao, and Yingjun Wang
Langmuir 2015 Volume 31(Issue 24) pp:6797-6806
Publication Date(Web):June 15, 2015
DOI:10.1021/acs.langmuir.5b01018
Most organs and tissues are composed of more than one type of cell that is spatially separated and located in different regions. This study used a microgrooved poly(lactic-co-glycolic acid) (PLGA) substrate to guide two types of cocultured cells to two spatially separated regions. Specifically, PC12 pheochromocytoma cells are guided to the inside of microgrooves, whereas NIH3T3 fibroblasts are guided to the ridge area in between neighboring parallel microgrooves. In addition, the microgrooved structures can significantly promote the proliferation and neural differentiation of PC12 cells as well as the osteogenic differentiation of NIH3T3 cells. Therefore, the microgrooved PLGA surface with separated PC12 and NIH3T3 cells can serve as a potential model system for studying nerve reconstruction in bone-repairing scaffolds.
Co-reporter:Meng Wang, Ye Zhu, and Chuanbin Mao
Langmuir 2015 Volume 31(Issue 25) pp:7084-7090
Publication Date(Web):June 19, 2015
DOI:10.1021/acs.langmuir.5b01151
Fingerprints at crime scenes are usually latent. The powder-dusting method is the most commonly used procedure for developing latent fingerprints in forensic science. However, the traditional powder-dusting method has characteristics of low sensitivity, low contrast, high background noise, and high autofluorescence interference. To overcome the drawbacks faced by the traditional method, we first optimized an oleic acid-based solvothermal approach for the synthesis of NaYF4:Yb,Er fluorescent upconversion nanoparticles (UCNPs) with the highest possible fluorescence intensity under near-infrared (NIR) irradiation. To optimize the synthesis, we studied the effects of the reaction time, reaction temperature, and volume of oleic acid on the size, phase composition, and UC fluorescence intensity of the UCNPs. We then used the resultant UCNPs to fluorescently label the fingerprints on various smooth substrates to improve the development of latent fingerprints because the UCNPs could undergo excitation under 980 nm NIR light to emit visible light. Latent fingerprints on three major types of smooth substrates were studied, including those with a single background color (transparent glass, white ceramic tiles, and black marbles), with multiple background colors (marbles with different complex surface patterns) and with strong background autofluorescence (note papers, Chinese paper money, and plastic plates). Compared with fingerprint development using traditional powders such as bronze powder, magnetic powder, and green fluorescent powder, our development procedure using UCNPs is facile and exhibits very high sensitivity, high contrast, low background interference, and low autofluorescence interference. This work shows that UCNPs synthesized under optimized conditions are a versatile fluorescent label for the facile development of fingerprints and can find their practical applications in forensic sciences.
Co-reporter:Yicun Wang, Zhigang Ju, Binrui Cao, Xiang Gao, Ye Zhu, Penghe Qiu, Hong Xu, Pengtao Pan, Huizheng Bao, Li Wang, and Chuanbin Mao
ACS Nano 2015 Volume 9(Issue 4) pp:4475
Publication Date(Web):April 9, 2015
DOI:10.1021/acsnano.5b01074
Candida albicans (C. albicans) infection causes high mortality rates within cancer patients. Due to the low sensitivity of the current diagnosis systems, a new sensitive detection method is needed for its diagnosis. Toward this end, here we exploited the capability of genetically displaying two functional peptides, one responsible for recognizing the biomarker for the infection (antisecreted aspartyl proteinase 2 IgG antibody) in the sera of cancer patients and another for binding magnetic nanoparticles (MNPs), on a single filamentous fd phage, a human-safe bacteria-specific virus. The resultant phage is first decorated with MNPs and then captures the biomarker from the sera. The phage-bound biomarker is then magnetically enriched and biochemically detected. This method greatly increases the sensitivity and specificity of the biomarker detection. The average detection time for each serum sample is only about 6 h, much shorter than the clinically used gold standard method, which takes about 1 week. The detection limit of our nanobiotechnological method is approximately 1.1 pg/mL, about 2 orders of magnitude lower than that of the traditional antigen-based method, opening up a new avenue to virus-based disease diagnosis.Keywords: fungal infection; nanofibers; nanoparticles; peptides; viruses;
Co-reporter:Chengyun Ning, Lei Zhou, Ye Zhu, Ying Li, Peng Yu, Shuangying Wang, Tianrui He, Weiping Li, Guoxin Tan, Yingjun Wang, and Chuanbin Mao
Langmuir 2015 Volume 31(Issue 50) pp:13561-13570
Publication Date(Web):December 11, 2015
DOI:10.1021/acs.langmuir.5b03699
The effect of cations in the surrounding solutions on the surface degradation of magnesium alloys, a well-recognized biodegradable biomaterial, has been neglected compared with the effect of anions in the past. To better simulate the compressive environment where magnesium alloys are implanted into the body as a cardiovascular stent, a device is designed and employed in the test so that a pressure, equivalent to the vascular pressure, can be directly applied to the magnesium alloy implants when the alloys are immersed in a medium containing one of the cations (K+, Na+, Ca2+, and Mg2+) found in blood plasma. The surface degradation behaviors of the magnesium alloys in the immersion test are then investigated using hydrogen evolution, mass loss determination, electron microscopy, pH value, and potentiodynamic measurements. The cations are found to promote the surface degradation of the magnesium alloys with the degree decreased in the order of K+ > Na+ > Ca2+ > Mg2+. The possible mechanism of the effects of the cations on the surface degradation is also discussed. This study will allow us to predict the surface degradation of magnesium alloys in the physiological environment and to promote the further development of magnesium alloys as biodegradable biomaterials.
Co-reporter:Meng Wang;Ming Li;Mingying Yang;Xiaomei Zhang;Aoyang Yu;Ye Zhu
Nano Research 2015 Volume 8( Issue 6) pp:1800-1810
Publication Date(Web):2015 June
DOI:10.1007/s12274-014-0686-6
The most commonly found fingermarks at crime scenes are latent and, thus, an efficient method for detecting latent fingermarks is very important. However, traditional developing techniques have drawbacks such as low detection sensitivity, high background interference, complicated operation, and high toxicity. To tackle this challenge, we employed fluorescent NaYF4:Yb,Er upconversion nanoparticles (UCNPs), which can fluoresce visible light when excited by 980 nm human-safe near-infrared light, to stain the latent fingermarks on various substrate surfaces. The UCNPs were successfully used as a novel fluorescent label for the detection of latent fingermarks with high sensitivity, low background, high efficiency, and low toxicity on various substrates including non-infiltrating materials (glass, marble, aluminum alloy sheets, stainless steel sheets, aluminum foils, and plastic cards), semi-infiltrating materials (floor leathers, ceramic tiles, wood floor, and painted wood), and infiltrating materials such as various types of papers. This work shows that UCNPs are a versatile fluorescent label for the facile detection of fingermarks on virtually any material, enabling their practical applications in forensic sciences.
Co-reporter:Pengtao Pan;Yicun Wang;Ye Zhu;Xiang Gao;Zhigang Ju;Penghe Qiu
Nano Research 2015 Volume 8( Issue 11) pp:3562-3570
Publication Date(Web):2015 November
DOI:10.1007/s12274-015-0856-1
The presence of anti-p53 antibody in serum is a biomarker for cancer. However, its high sensitivity detection is still an issue in cancer diagnosis. To tackle this challenge, we used fd phage, a human-safe bacteria-specific virus nanofiber that can be mass-produced by infecting host bacteria in an error-free manner, and genetically engineered it to display a peptide capable of recognizing and capturing anti-p53 antibody on its side wall. We employed the resultant phage nanofibers as a capture probe to develop a modified version of the enzyme-linked immunosorbent assay (ELISA) method, termed phage-ELISA. We compared it to the traditional ELISA method for the detection of anti-p53 antibody, p53-ELISA, which uses recombinant wild-type p53 protein to capture anti-p53 antibody. We applied phage-ELISA to detect anti-p53 antibody in an experimental group of 316 patients with various types of malignant tumors. We found that a detection rate of 17.7% (56 positive cases) was achieved by phage-ELISA, which was comparable to the detection rate of 20.6% for p53-ELISA (65 positive cases). However, when both phage and p53 were combined to form antibody-capturing probes for phage/p53-ELISA, a detection rate of 30.4% (96 positive cases) was achieved. Our work showed that owing to the combined capture of the anti-p53 antibody by both phage nanofibers and p53, the phage/p53-ELISA achieved the highest diagnostic accuracy and detection efficiency for the anti-p53 antibody in patients with various types of cancers. Our work suggests that a combination of nanofibers and antigens, both of which capture antibody, could lead to increased detection sensitivity, which is useful for applications in the life sciences, clinical medicine, and environmental sciences.
Co-reporter:Binrui Cao;Mingying Yang;Ye Zhu;Xuewei Qu
Advanced Materials 2014 Volume 26( Issue 27) pp:4627-4631
Publication Date(Web):
DOI:10.1002/adma.201401550
Co-reporter:Jianglin Wang;Mingying Yang;Ye Zhu;Lin Wang;Antoni P. Tomsia
Advanced Materials 2014 Volume 26( Issue 29) pp:4961-4966
Publication Date(Web):
DOI:10.1002/adma.201400154
Co-reporter:Ammaji Rajala, Yuhong Wang, Ye Zhu, Michelle Ranjo-Bishop, Jian-Xing Ma, Chuanbin Mao, and Raju V. S. Rajala
Nano Letters 2014 Volume 14(Issue 9) pp:5257-5263
Publication Date(Web):August 12, 2014
DOI:10.1021/nl502275s
Application of viruses as a carrier, though not safe, to deliver genes to eye tissue was successful. However, a safer, nonviral, biocompatible lipid-based nanoparticle has never been tested to treat blinding eye diseases. We created an artificial virus using a nanoparticle, liposome-protamine-DNA complex (LPD), modified with a cell permeable peptide and a nuclear localization signaling (NLS) peptide, to deliver a functional gene for eye disease treatment. In the eye, a photochemical, 11-cis-retinal, allows the visual pigment rhodopsin to absorb light in the visible range. Without the photochemical, we lose the ability to see light. Retinal pigment epithelium protein 65 (Rpe65) is the key enzyme in regulating the availability of photochemical; deficiency of this gene results in a blinding eye disease. Here we show for the first time that LPD promotes efficient delivery in a cell specific-manner, and a long-term expression of Rpe65 gene to mice lacking Rpe65 gene, leading to in vivo correction of blindness. Thus, LPD nanoparticles could provide a promising, efficient, nonviral method of gene delivery with clinical applications in eye disease treatment.
Co-reporter:Jianglin Wang, Lin Wang, Mingying Yang, Ye Zhu, Antoni Tomsia, and Chuanbin Mao
Nano Letters 2014 Volume 14(Issue 12) pp:6850-6856
Publication Date(Web):December 2, 2014
DOI:10.1021/nl504358j
Here we report the design of a unique matrix, assembled from engineered M13 phage bionanofibers with specific cues of nanotopographies and versatile signal peptides to simulate native niche for directing the fate of induced pluripotent stem cells (iPSCs). By independently varying the peptide sequences and nanotopographies, we find that the resident iPSCs on the phage matrix are first differentiated into mesenchymal progenitor cells (MPCs), which are further differentiated into osteoblasts in the absence of osteogenic supplements due to the elongation induced by phage nanofibers. The phage-based matrix represents not only a biomimetic stem cell niche enabling independently varying biochemical and biophysical cues in one system but also a substrate for generating a safe and efficient cell source for tissue engineering.
Co-reporter:Lijing Hao, Hui Yang, Chang Du, Xiaoling Fu, Naru Zhao, Suju Xu, Fuzhai Cui, Chuanbin Mao and Yingjun Wang
Journal of Materials Chemistry A 2014 vol. 2(Issue 30) pp:4794-4801
Publication Date(Web):27 Jun 2014
DOI:10.1039/C4TB00597J
Self-assembled monolayers (SAMs) of alkanethiols on gold have been employed as model substrates to investigate the effects of surface chemistry on cell behavior. However, few studies were dedicated to substrates with controlled wettability in studying the stem cell fate. Here, mixed hydroxyl (–OH) and methyl (–CH3) terminated SAMs were prepared to form substrates with varying wettability, which were used to study the effects of wettability on the adhesion, spreading, proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) from human and mouse origins. The numbers of adhered human fetal MSCs (hMSCs) and mouse bone marrow MSCs (mMSCs) were maximized on –OH/–CH3 mixed SAMs with water contact angles of 40–70° and 70–90°, respectively. Hydrophilic mixed SAMs with a water contact angle of 20–70° also promoted the spreading of both hMSCs and mMSCs. Proliferation of both hMSCs and mMSCs was most favored on hydrophilic SAMs with a water contact angle around 70°. In addition, a moderate hydrophilic surface (with a contact angle of 40–90° for hMSCs and 70° for mMSCs) promoted osteogenic differentiation in the presence of biological stimuli. Hydrophilic mixed SAMs with a moderate wettability tended to promote the expression of αvβ1 integrin of MSCs, indicating that the tunable wettability of the mixed SAMs may guide osteogenesis through mediating the αvβ1 integrin signaling pathway. Our work can direct the design of biomaterials with controllable wettability to promote the adhesion, proliferation and differentiation of MSCs from different sources.
Co-reporter:Lihua Li, Mei Li, Dan Li, Peng He, Hong Xia, Yu Zhang and Chuanbin Mao
Journal of Materials Chemistry A 2014 vol. 2(Issue 36) pp:5952-5961
Publication Date(Web):28 Jul 2014
DOI:10.1039/C4TB00666F
A great challenge in orthopedic tumor operation faced by orthopedic implants is the high recurrence and metastasis of bone tumor as well as the bacterial infection associated with the implants. Thus ideal titanium (Ti)-based bone implants should be able to not only inhibit cancer cell adhesion and proliferation, and promote cancer cell apoptosis, but also resist bacterial infections. Towards this end, we developed a new approach to modify the surface of Ti-based bone implants so that they can restrain functions of osteoclastoma (giant cell tumor of bone) cancer cells (GCTs) and inhibit the adhesion of bacteria. First, the surface of pristine Ti substrates was functionalized with dopamine (DA) to form DA–Ti substrates. Then nanoparticles electrostatically assembled from poly-lysine (PLL) and heparin (Hep) were chemically immobilized onto the DA–Ti substrates to form PLL/Hep–Ti substrates. Chitosan (CH) and methotrexate (MTX) were then electrostatically immobilized onto the PLL/Hep–Ti substrates to generate CH–MTX–Ti substrates. The successful functionalization of the Ti substrates was confirmed by X-ray photoelectron spectroscopy. GCTs cultured on differently functionalized Ti substrates were investigated in terms of cell adhesion, cytoskeleton, proliferation, cytotoxicity and apoptosis. The growth of Staphylococcus aureus bacteria in the presence of different substrates was also assayed. Our results showed that CH–MTX–Ti substrates not only significantly inhibited the adhesion, proliferation and viability of GCTs, and promoted the apoptosis of GCTs, but also prevented the adhesion of the bacteria and the subsequent formation of bacterial biofilms, when compared to other Ti substrates. Thus CH–MTX–Ti substrates are expected to be used as orthopedic prostheses in bone tumor surgery that can inhibit both osteoclastoma formation and bacterial infection.
Co-reporter:Jingwen Liao, Ye Zhu, Zhaoyi Yin, Guoxin Tan, Chengyun Ning and Chuanbin Mao
Journal of Materials Chemistry A 2014 vol. 2(Issue 45) pp:7872-7876
Publication Date(Web):21 Oct 2014
DOI:10.1039/C4TB01053A
Citric acid, a molecule present in fresh bone, was introduced into template-free electrochemical polymerization to form biocompatible coating made of polypyrrole (PPy) nano-cones on bone implants. It served not only as a dopant to tune the nano-architectures but also as a promoter to enhance bioactivity of the PPy-coated implants.
Co-reporter:Mingying Yang, Yajun Shuai, Guanshan Zhou, Namita Mandal, Liangjun Zhu, and Chuanbin Mao
ACS Applied Materials & Interfaces 2014 Volume 6(Issue 16) pp:13782
Publication Date(Web):July 22, 2014
DOI:10.1021/am503214g
Bombyx mori (B. mori) silk sericin is a protein with features desirable as a biomaterial, such as increased hydrophilicity and biodegradation, as well as resistance to oxidation, bacteria, and ultraviolet light. In contrast to other widely studied B. mori silk proteins such as fibroin, sericin is still unexplored as a building block for fabricating biomaterial, and thus a facile technique of processing it into a material is needed. Here, electrospinning technology was used to fabricate it into biomaterials from two forms of B. mori silk sericin with different molecular weights, one is a low (12.0 kDa) molecular sericin (LS) form and another is a high (66.0 kDa) molecular weight sericin (HS) form. Circular dichroism (CD) spectra showed that LS in hexafluoroacetone (HFA) solvent adopted a predominantly random coil conformation, whereas HS tended to form a β-sheet structure along with a large content of random coils. In addition, LS and HS in HFA solvent were found to form cylinder-like smaller nanoparticles and larger irregular aggregates before electrospinning, respectively. As a result, biomaterials based on microparticles and nanofibers were successfully fabricated by electrospinning of LS and HS dissolved in HFA, respectively. The cell viability and differentiation assay indicated that nanofibers and microparticles improved cell adhesion, growth, and differentiation, proving that the scaffolds electrospun from sericin are biocompatible regardless of its molecular weight. The microparticles, not common in electrospinning of silk proteins reported previously, were found to promote the osteogenic differentiation of mesenchymal stem cells in comparison to the nanofibers. This study suggested that molecular weight of sericin mediates its secondary structure and assembly structure, which in turn leads to a control of final morphology of the electrospun materials. The microparticles and nanofibers of sericin can be potentially used as building blocks for fabricating the scaffolds for tissue engineering.Keywords: Bombyx mori (B. mori) silk sericin; electrospinning; microparticles; nanofibers
Co-reporter:Alessandro Polini, Jianglin Wang, Hao Bai, Ye Zhu, Antoni P. Tomsia and Chuanbin Mao
Biomaterials Science 2014 vol. 2(Issue 12) pp:1779-1786
Publication Date(Web):07 Aug 2014
DOI:10.1039/C4BM00164H
Hydroxyapatite (HA), the principal component of bone mineral, shows osteoconductive properties when employed for coating metal implants as well as scaffold materials in synthetic bone grafts. With the goal of providing this material with osteoinductive capabilities to promote faster bone regeneration, we show an easy approach to functionalize HA implant surfaces and enrich them with osteoinductive properties by the use of HA-binding modular peptides. The modular peptides are designed as a combination of two domains, an HA-binding peptide motif and an osteogenic peptide motif derived from the osteogenic growth peptide (OGP) or bone morphometric protein 7 (BMP-7). To identify the best HA-binding peptide, several nature-inspired peptides derived from natural bone extracellular matrix proteins (bone sialoprotein, osteonectin, osteocalcin, and salivarin statherin) were compared for HA-binding activity, revealing concentration-dependent and incubation-time-dependent behaviours. We discovered that a Poly-E heptamer (E7) is the best HA-binding peptide, and thus combined it with a second osteogenic peptidic domain to create an osteoinductive modular peptide. After binding/release characterization, we found that the addition of the second osteogenic peptide domain did not change the binding profile of the modular peptides and caused only a slight change in their release kinetics. Mesenchymal stem cells (MSCs) were cultured on the HA substrates functionalized with modular peptides, and cell adhesion, proliferation, and differentiation in a basal medium (i.e., without any osteogenic supplements) were investigated. Gene expression data clearly showed that MSCs were committed to differentiate into osteoblasts in the presence of the modular peptides. HA discs functionalized with the E7 BMP-7 modular peptide showed the best capability in inducing the osteogenic differentiation of MSCs among all modular peptides studied. The modular peptides can easily be used to functionalize the HA implants through its constituent HA-binding motif, leaving the osteogenic peptide motif protruding from the surface for inducing osteogenesis. Our work opens up a new approach to the formulation of new bioactive HA coatings and implants for bone and dental repair.
Co-reporter:Mingying Yang, Yajun Shuai, Can Zhang, Yuyin Chen, Liangjun Zhu, Chuanbin Mao, and Hongwei OuYang
Biomacromolecules 2014 Volume 15(Issue 4) pp:
Publication Date(Web):March 26, 2014
DOI:10.1021/bm401740x
Biomacromolecules have been used as templates to grow hydroxyapatite crystals (HAps) by biomineralization to fabricate mineralized materials for potential application in bone tissue engineering. Silk sericin is a protein with features desirable as a biomaterial, such as increased hydrophilicity and biodegradation. Mineralization of the silk sericin from Antheraea pernyi (A. pernyi) silkworm has rarely been reported. Here, for the first time, nucleation of HAps on A. pernyi silk sericin (AS) was attempted through a wet precipitation method and consequently the cell viability and osteogenic differentiation of BMSCs on mineralized AS were investigated. It was found that AS mediated the nucleation of HAps in the form of nanoneedles while self-assembling into β-sheet conformation, leading to the formation of a biomineralized protein based biomaterial. The cell viability assay of BMSCs showed that the mineralization of AS stimulated cell adhesion and proliferation, showing that the resultant AS biomaterial is biocompatible. The differentiation assay confirmed that the mineralized AS significantly promoted the osteogenic differentiation of BMSCs when compared to nonmineralized AS as well as other types of sericin (B. mori sericin), suggesting that the resultant mineralized AS biomaterial has potential in promoting bone formation. This result represented the first work proving the osteogenic differentiation of BMSCs directed by silk sericin. Therefore, the biomineralization of A. pernyi silk sericin coupled with seeding BMSCs on the resultant mineralized biomaterials is a useful strategy to develop the potential application of this unexplored silk sericin in the field of bone tissue engineering. This study lays the foundation for the use of A. pernyi silk sericin as a potential scaffold for tissue engineering.
Co-reporter:Jingwen Liao;Ye Zhu;Zhengnan Zhou;Junqi Chen;Guoxin Tan; Chengyun Ning; Chuanbin Mao
Angewandte Chemie International Edition 2014 Volume 53( Issue 48) pp:13068-13072
Publication Date(Web):
DOI:10.1002/anie.201406349
Abstract
A facile method is needed to control the protein adsorption onto biomaterials, such as, bone implants. Herein we doped taurocholic acid (TCA), an amphiphilic biomolecule, into an array of 1D nano-architectured polypyrrole (NAPPy) on the implants. Doping TCA enabled the implant surface to show reversible wettability between 152° (superhydrophobic, switch-on state) and 55° (hydrophilic, switch-off state) in response to periodically switching two weak electrical potentials (+0.50 and −0.80 V as a switch-on and switch-off potential, respectively). The potential-switchable reversible wettability, arising from the potential-tunable orientation of the hydrophobic and hydrophilic face of TCA, led to potential-switchable preferential adsorption of proteins as well as cell adhesion and spreading. This potential-switchable strategy may open up a new avenue to control the biological activities on the implant surface.
Co-reporter:Penghe Qiu;Xuewei Qu;Daniel J. Brackett;Megan R. Lerner;Dong Li
Advanced Materials 2013 Volume 25( Issue 17) pp:2492-2496
Publication Date(Web):
DOI:10.1002/adma.201204472
Co-reporter:Kun Ma;Dong-Dong Wang;Yiyang Lin;Jianglin Wang;Valery Petrenko
Advanced Functional Materials 2013 Volume 23( Issue 9) pp:1172-1181
Publication Date(Web):
DOI:10.1002/adfm.201102963
Abstract
An important criterion for effective gene therapy is sufficient chromosomal integration activity. The Sleeping Beauty (SB) transposon system is a plasmid system allowing efficient insertion of transgenes into the host genome. However, such efficient insertion occurs only after the system is delivered to nuclei. Since transposons do not have the transducing abilities of viral vectors, efficient delivery of this system first into cells and then into cell nuclei is still a challenge. Here, a phage display technique using a major coat displayed phage library is employed to identify a peptide (VTAMEPGQ) that can home to rat mesenchymal stem cells (rMSCs). A nanoparticle, called liposome protamine/DNA lipoplex (LPD), is electrostatically assembled from cationic liposomes and an anionic complex of protamine, DNA and targeting peptides. Various peptides are enveloped inside the LPD to improve its targeting capability for rMSCs and nuclei. The rMSC-targeting peptide and nuclear localization signal (NLS) peptide can execute the synergetic effect to promote transfection action of LPD. The homing peptide directs the LPD to target the MSCs, whereas the NLS peptide directs transposon to accumulate into nuclei once LPD is internalized inside the cells, leading to increased gene expression. This suggests that rMSC-targeting peptide and NLS peptide within LPD can target to rMSCs and then guide transposon into nuclei. After entering the nuclei, SB transposon increase the insertion rates into cellular chromosomes. The targeting LPD does not show obvious cell toxicity and influence on the differentiation potential of rMSCs. Therefore, the integration of SB transposon and LPD system is a promising nonviral gene delivery vector in stem cell therapy.
Co-reporter:Dong Li, Ye Zhu and Chuanbin Mao
Journal of Materials Chemistry A 2013 vol. 1(Issue 40) pp:5515-5520
Publication Date(Web):09 Sep 2013
DOI:10.1039/C3TB20733A
A green one-pot approach is used to synthesize surface morphology controlled hollow silica spheres in aqueous solution under ambient conditions. Using cationic polystyrene particles as templates and aminopropyltriethoxysilane (APTES) as a structure directing agent, the surface roughness and wall thickness could be easily controlled by varying the concentration of tetraethoxysilane (TEOS). The smooth surface of hollow silica spheres with different wall thicknesses was obtained using anionic polystyrene particles. The resulting hollow silica spheres with a rough surface had better performance in carrying and releasing a model drug.
Co-reporter:Naveen Gra;Dong-Dong Wang;Ye Zhu ; Chuanbin Mao
Angewandte Chemie International Edition 2013 Volume 52( Issue 43) pp:11278-11281
Publication Date(Web):
DOI:10.1002/anie.201301113
Co-reporter:Naveen Gra;Dong-Dong Wang;Ye Zhu ; Chuanbin Mao
Angewandte Chemie 2013 Volume 125( Issue 43) pp:11488-11491
Publication Date(Web):
DOI:10.1002/ange.201301113
Co-reporter:Binrui Cao;Ye Zhu;Lin Wang ; Chuanbin Mao
Angewandte Chemie 2013 Volume 125( Issue 45) pp:11966-11970
Publication Date(Web):
DOI:10.1002/ange.201303854
Co-reporter:Binrui Cao;Ye Zhu;Lin Wang ; Chuanbin Mao
Angewandte Chemie International Edition 2013 Volume 52( Issue 45) pp:11750-11754
Publication Date(Web):
DOI:10.1002/anie.201303854
Co-reporter:Fuke Wang, Susan L. Nimmo, Binrui Cao and Chuanbin Mao
Chemical Science 2012 vol. 3(Issue 8) pp:2639-2645
Publication Date(Web):15 May 2012
DOI:10.1039/C2SC00583B
Biomimetic silica formation is strongly dependent on the presence of cationic amine groups which hydrolyze organosilicate precursors and bind to silicate oligomers. Since most biological species possess anionic surfaces, the dependence on amine groups limits utilization of biotemplates for fabricating materials with specific morphologies and pore structures. Here, we report a general aminopropyltriethoxysilane (APTES) directed method for preparing hollow silica with well-defined morphologies using varying biotemplates (proteins, viruses, flagella, bacteria and fungi). Control experiments, pH evolution measurements and 29Si NMR spectroscopic studies have revealed a mechanism of the assembly of APTES on bio-surfaces with subsequent nucleation and growth of silica. The APTES assembly and nuclei formation on bio-surfaces ensured precise transcription of the morphologies of biotemplates to the resulting silica. This method could be extended to the preparation of other oxides.
Co-reporter:Dong Li, Xuewei Qu, Salete M. C. Newton, Philip E. Klebba and Chuanbin Mao
Journal of Materials Chemistry A 2012 vol. 22(Issue 31) pp:15702-15709
Publication Date(Web):21 May 2012
DOI:10.1039/C2JM31034A
Bacterial flagella are naturally occurring self-assembling protein nanofibers protruding from the bacterial surface to assist the swimming of bacteria. They are rigid and exhibit diverse morphologies depending on the ionic strength, the pH values, temperature, and subunit sequences. Here, silica nanotubes (SNTs) with controllable morphologies were synthesized using flagella as biological templates in aqueous solution under mild conditions. The morphologies and surface features of flagella-templated SNTs can be simply tuned by adjusting the pH value or surface chemistry of flagella by peptide display. A variety of different morphologies (coiled, straight, and curly with different wavelengths) and surface features (smooth, rough, granular and pearl-necklace-like) of SNTs were obtained. When pH varies from acidic to alkaline conditions, in general, SNTs varied from bundled coiled, to characteristic sinusoidal waves, helical, and straight morphologies. Under genetic control, flagella displaying negatively charged peptides exhibited thinner layer of silica condensation but a rougher surface. However, flagella with positively charged peptide inserts induced the deposition of a thicker silica shell with a smoother surface. Incorporation of hydroxyl bearing amino acid residues such as Ser into the peptide displayed on flagella highly enhanced the biotemplated deposition of silica. This work suggests that bacterial flagella are promising biotemplates for developing an environmentally benign and cost-efficient approach to morphology-controlled synthesis of nanotubes. Moreover, the dependency of the thickness of the silica shell on the peptides displayed on flagella helps us to further understand the mechanism of biomimetic nucleation of silica on biological templates.
Co-reporter:Jingpu Zhang, Congcong Mi, Hongyan Wu, Huaiqing Huang, Chuanbin Mao, Shukun Xu
Analytical Biochemistry 2012 Volume 421(Issue 2) pp:673-679
Publication Date(Web):15 February 2012
DOI:10.1016/j.ab.2011.11.008
High-quality NaYF4:Yb/Er/Gd up-conversion nanoparticles (UCNPs) were first synthesized by a solvothermal method using rare earth stearate, sodium fluoride, ethanol, water, and oleic acid as precursors. Doped Gd3+ ions can promote the transition of NaYF4 from cubic to hexagonal phase, shorten the reaction time, and reduce the reaction temperature without reducing the luminescence intensity of NaYF4:Yb/Er UCNPs. X-ray diffraction, infrared spectroscopy, transmission electron microscopy, and luminescence spectroscopy were applied to characterize the UCNPs. The nanoparticles exhibited small size and excellent green up-conversion photoluminescence, making them suitable for biological applications. After the surfaces of NaYF4:Yb/Er/Gd UCNPs were modified with amino groups through the Stöber method, they could be brought close enough to the analytically important protein called R-phycoerythrin (R-PE) bearing multiple carboxyl groups so that energy transfer could occur. A luminescence resonance energy transfer (LRET) system was developed using NaYF4:Yb/Er/Gd UCNPs as an energy donor and R-PE as an energy acceptor. As a result, a detection limit of R-PE of 0.5 μg/ml was achieved by the LRET system with a relative standard deviation of 2.0%. Although this approach was first used successfully to detect R-PE, it can also be extended to the detection of other biological molecules.
Co-reporter: Chuanbin Mao;Fuke Wang ;Binrui Cao
Angewandte Chemie 2012 Volume 124( Issue 26) pp:6517-6521
Publication Date(Web):
DOI:10.1002/ange.201107824
Co-reporter: Chuanbin Mao;Fuke Wang ;Binrui Cao
Angewandte Chemie International Edition 2012 Volume 51( Issue 26) pp:6411-6415
Publication Date(Web):
DOI:10.1002/anie.201107824
Co-reporter:Dong Li, Salete M. C. Newton, Philip E. Klebba, and Chuanbin Mao
Langmuir 2012 Volume 28(Issue 47) pp:16338-16346
Publication Date(Web):November 14, 2012
DOI:10.1021/la303237u
A bacterial flagellum is self-assembled primarily from thousands of flagellin (FliC), a protein subunit. A foreign peptide can be fully displayed on the surface of the flagellum through inserting it into every constituent protein subunit. To shed light on the role of bone proteins during the nucleation of hydroxyapatite (HAP), representative domains from type I collagen, including part of the N-,C-terminal, N-,C-zone around the hole zone and an eight repeat unit Gly-Pro-Pro (GPP8) sequence similar to the central sequence of type I collagen, were separately displayed on the surface of the flagella. Moreover, eight negatively charged, contiguous glutamic acid residues (E8) and two other characteristic sequences derived from a representative noncollagenous protein called bone sialoprotein (BSP) were also displayed on flagella. After being incubated in an HAP supersaturated precursor solution, flagella displaying E8 or GPP8 sequences were found to be coated with a layer of HAP nanocrystals. Very weak or no nucleation was observed on flagella displaying other peptides being tested. We also found that calcium ions can induce the assembly of the negatively charged E8 flagella into bundles mimicking collagen fibers, followed by the formation of HAP nanocrystals with the crystallographic c axis preferentially aligned with long axis of flagella, which is similar to that along the collagen fibrils in bone. This work demonstrates that because of the ease of the peptide display on flagella and the self-assembly of flagella, flagella can serve as a platform for studying biomineralization and as a building block to generate bonelike biomaterials.
Co-reporter:Penghe Qiu
Advanced Materials 2011 Volume 23( Issue 42) pp:4880-4885
Publication Date(Web):
DOI:10.1002/adma.201102636
Co-reporter:Wei Xie, Penghe Qiu and Chuanbin Mao
Journal of Materials Chemistry A 2011 vol. 21(Issue 14) pp:5190-5202
Publication Date(Web):11 Jan 2011
DOI:10.1039/C0JM03301D
Surface-enhanced Raman scattering (SERS) is a phenomenon that occurs on nanoscale-roughed metallic surface. The magnitude of the Raman scattering signal can be greatly enhanced when the scatterer is placed in the very close vicinity of the surface, which enables this phenomenon to be a highly sensitive analytical technique. SERS inherits the general strongpoint of conventional Raman spectroscopy and overcomes the inherently small cross section problem of a Raman scattering. It is a sensitive and nondestructive spectroscopic method for biological samples, and can be exploited either for the delivery of molecular structural information or for the detection of trace levels of analytes. Therefore, SERS has long been regarded as a powerful tool in biomedical research. Metallic nanostructure plays a key role in all the biomedical applications of SERS because the enhanced Raman signal can only be obtained on the surface of a finely divided substrate. This review focuses on progress made in the use of SERS as an analytical technique in bio-imaging, analysis and detection. Recent progress in the fabrication of SERS active nanostructures is also highlighted.
Co-reporter:Jing Chen, Changrun Guo, Meng Wang, Lei Huang, Liping Wang, Congcong Mi, Jing Li, Xuexun Fang, Chuanbin Mao and Shukun Xu
Journal of Materials Chemistry A 2011 vol. 21(Issue 8) pp:2632-2638
Publication Date(Web):06 Jan 2011
DOI:10.1039/C0JM02854A
β-NaYF4:Yb,Er upconversion nanoparticles (UCNPs) can emit bright green fluorescence under near-infrared (NIR) light excitation which is safe to the body and can penetrate deeply into tissues. The application of UCNPs in biolabeling and imaging has received great attention recently. In this work, β-NaYF4:Yb,Er UCNPs with an average size of 35 nm, uniformly spherical shape, and surface modified with amino groups were synthesized by a one-step green solvothermal approach through the use of room-temperature ionic liquids as the reactant, co-solvent and template. The as-prepared UCNPs were introduced into Caenorhabditis elegans (C. elegans) to achieve successful in vivo imaging. We found that longer incubation time, higher UCNP concentration and smaller UCNP size can make the in vivo fluorescence of C. elegans much brighter and more continuous along their body. The worms have no apparent selectivity on ingestion of the UCNPs capped with different capping ligands while having similar size and shape. The next generation of worms did not show fluorescence under excitation. In addition, low toxicity of the nanoparticles was demonstrated by investigating the survival rates of the worms in the presence of the UCNPs. Our work demonstrates the potential application of the UCNPs in studying the biological behavior of organisms, and lays the foundation for further development of the UCNPs in the detection and diagnosis of diseases.
Co-reporter:Haibao Zhu, Binrui Cao, Zipeng Zhen, Ayyagari A. Laxmi, Dong Li, Shaorong Liu, Chuanbin Mao
Biomaterials 2011 32(21) pp: 4744-4752
Publication Date(Web):
DOI:10.1016/j.biomaterials.2011.03.030
Co-reporter:Hong Xu, Binrui Cao, Anne George, and Chuanbin Mao
Biomacromolecules 2011 Volume 12(Issue 6) pp:
Publication Date(Web):April 26, 2011
DOI:10.1021/bm200274r
Bioinspired mineralization is an innovative approach to the fabrication of bone biomaterials mimicking the natural bone. Bone mineral hydroxylapatite (HAP) is preferentially oriented with c-axis parallel to collagen fibers in natural bone. However, such orientation control is not easy to achieve in artificial bone biomaterials. To overcome the lack of such orientation control, we fabricated a phage-HAP composite by genetically engineering M13 phage, a nontoxic bionanofiber, with two HAP-nucleating peptides derived from one of the noncollagenous proteins, Dentin Matrix Protein-1 (DMP1). The phage is a biological nanofiber that can be mass produced by infecting bacteria and is nontoxic to human beings. The resultant HAP-nucleating phages are able to self-assemble into bundles by forming β-structure between the peptides displayed on their side walls. The β-structure further promotes the oriented nucleation and growth of HAP crystals within the nanofibrous phage bundles with their c-axis preferentially parallel to the bundles. We proposed that the preferred orientation resulted from the stereochemical matching between the negatively charged amino acid residues within the β-structure and the positively charged calcium ions on the (001) plane of HAP crystals. The self-assembly and mineralization driven by the β-structure formation represent a new route for fabricating mineralized fibers that can serve as building blocks in forming bone repair biomaterials and mimic the basic structure of natural bones.
Co-reporter:Congcong Mi, Zhenhuang Tian, Can Cao, Zhijia Wang, Chuanbin Mao, and Shukun Xu
Langmuir 2011 Volume 27(Issue 23) pp:14632-14637
Publication Date(Web):October 26, 2011
DOI:10.1021/la204015m
This work reports the novel microwave-assisted solvothermal synthesis and structural, topographic, spectroscopic characterization of NaYF4:Yb,Er upconversion nanoparticles (UCNPs) as well as their application in the labeling of HeLa cells. The nanoparticles were prepared in ethylene glycol, with rare earth acetates as precursor and NH4F and NaCl as the fluorine and sodium sources. X-ray diffraction, transmission electron microscopy, and luminescence spectroscopy were applied to characterize the nanoparticles. Experimental results showed that the microwave-assisted solvothermal method is an effective approach to create highly crystalline, strongly luminescent UCNPs at a lower temperature (160 °C) and within a significantly shortened reaction time (only 1 h) compared to the traditional methods. The effect of fluorine source on the optical properties of UCNPs was investigated by using NH4F, NH4HF2, NaF, and 1-butyl-3-methylimidazolium tetrafluoroborate (BmimBF4) as different fluorine sources; NH4F proved to be the best one, making the luminescent intensity increase at least 2 orders of magnitude. The UCNPs with four different colors (green, yellow, orange, and cyan) were successfully obtained. After being modified with amino groups and coupled with CEA-8 antibody, the obtained nanoparticles were successfully applied in the specific fluorescent immunolabeling and imaging of HeLa cells to further verify their function as a marker in immunolabeling.
Co-reporter:Binrui Cao;Hong Xu ;Dr. Chuanbin Mao
Angewandte Chemie International Edition 2011 Volume 50( Issue 28) pp:
Publication Date(Web):
DOI:10.1002/anie.201103580
Co-reporter:Binrui Cao;Hong Xu ;Dr. Chuanbin Mao
Angewandte Chemie 2011 Volume 123( Issue 28) pp:6388-6392
Publication Date(Web):
DOI:10.1002/ange.201102052
Co-reporter:Binrui Cao;Hong Xu ;Dr. Chuanbin Mao
Angewandte Chemie 2011 Volume 123( Issue 28) pp:
Publication Date(Web):
DOI:10.1002/ange.201103580
Co-reporter:Binrui Cao;Hong Xu ;Dr. Chuanbin Mao
Angewandte Chemie International Edition 2011 Volume 50( Issue 28) pp:6264-6268
Publication Date(Web):
DOI:10.1002/anie.201102052
Co-reporter:Fuke Wang, Binrui Cao and Chuanbin Mao
Chemistry of Materials 2010 Volume 22(Issue 12) pp:3630
Publication Date(Web):May 27, 2010
DOI:10.1021/cm902727s
Inorganic ions may direct the self-assembly of biomacromolecules into nanostructures which can further be used as a reactant and matrix for nanomaterials synthesis and assembly. Here we use bone mineral and filamentous bacteriophage as a model to demonstrate this concept. Divalent calcium ions are found to trigger the electrostatic self-assembly of anionic nanofiber-like bacteriophages into bundle structures where calcium ions are preorganized between bacteriophage nanofibers. The resultant Ca2+-bacteriophage bundles can be separated and purified from the aqueous solution. The nanostructures of the bundles are verified by zeta potential analysis, small-angle X-ray scattering and transmission electron microscopy. Because of the transcription of the bacteriophage chiral surface to the periodic alignment of preloaded Ca2+, the Ca2+-bacteriphage bundles can serve as both Ca sources and biotemplates to initiate the oriented nucleation and growth of nanocrystalline hydroxyapatite in phosphate solution or in simulated body fluid. This work provides new insights into biomineralization and represents a new approach to the fabrication of biomolecular-inorganic hybrid layered nanostructures.
Co-reporter:Pan Sun, Hongyan Zhang, Chang Liu, Jin Fang, Meng Wang, Jing Chen, Jingpu Zhang, Chuanbin Mao and Shukun Xu
Langmuir 2010 Volume 26(Issue 2) pp:1278-1284
Publication Date(Web):September 23, 2009
DOI:10.1021/la9024553
The synthesis of a new kind of magnetic, fluorescent multifunctional nanoparticles (∼30 nm in diameter) was demonstrated, where multiple fluorescent CdTe quantum dots (QDs) are covalently linked to and assembled around individual silica-coated superparamagnetic Fe3O4 nanoparticles and active carboxylic groups are presented on the surface for easy bioconjugation with biomolecules. The Fe3O4 nanoparticles were first functionalized with thiol groups, followed by chemical conjugation with multiple thioglycolic acid modified CdTe QDs to form water-soluble Fe3O4/CdTe magnetic/fluorescent nanocomposites. X-ray diffraction, infrared spectroscopy, transmission electron microscopy, absorption and fluorescence spectroscopy, and magnetometry were applied to fully characterize the multifunctional nanocomposites. The nanocomposites were found to exhibit magnetic and fluorescent properties favorable for their applications in magnetic separation and guiding as well as fluorescent imaging. The carboxyl groups on the nanocomposite surface were proved to be chemically active and readily available for further bioconjugation with biomolecules such as bovine serum albumin and antibodies, enabling the applications of the nanocomposites for specific recognition of biological targets. The Fe3O4/CdTe magnetic/fluorescent nanocomposites conjugated with anti-CEACAM8 antibody were successfully employed for immuno-labeling and fluorescent imaging of HeLa cells.
Co-reporter:Penghe Qiu and Chuanbin Mao
ACS Nano 2010 Volume 4(Issue 3) pp:1573
Publication Date(Web):February 16, 2010
DOI:10.1021/nn9009196
Branched hollow fibers are common in nature, but to form artificial fibers with a similar branched hollow structure is still a challenge. We discovered that polyvinylpyrrolidone (PVP) could self-assemble into branched hollow fibers in an aqueous solution after aging the PVP solution for about two weeks. On the basis of this finding, we demonstrated two approaches by which the self-assembly of PVP into branched hollow fibers could be exploited to template the formation of branched hollow inorganic fibers. First, inorganic material such as silica with high affinity against the PVP could be deposited on the surface of the branched hollow PVP fibers to form branched hollow silica fibers. To extend the application of PVP self-assembly in templating the formation of hollow branched fibers, we then adopted a second approach where the PVP molecules bound to inorganic nanoparticles (using gold nanoparticles as a model) co-self-assemble with the free PVP molecules in an aqueous solution, resulting in the formation of the branched hollow fibers with the nanoparticles embedded in the PVP matrix constituting the walls of the fibers. Heating the resultant fibers above the glass transition temperature of PVP led to the formation of branched hollow gold fibers. Our work suggests that the self-assembly of the PVP molecules in the solution can serve as a general method for directing the formation of branched hollow inorganic fibers. The branched hollow fibers may find potential applications in microfluidics, artificial blood vessel generation, and tissue engineering.Keywords: branched hollow fibers; gold; nanoparticles; polyvinylpyrrolidone; self-assembly; silica
Co-reporter:Aihua Liu;Gopal Abbineni
Advanced Materials 2009 Volume 21( Issue 9) pp:1001-1005
Publication Date(Web):
DOI:10.1002/adma.200800777
Co-reporter:Fuke Wang and Chuanbin Mao
Chemical Communications 2009 (Issue 10) pp:1222-1224
Publication Date(Web):13 Jan 2009
DOI:10.1039/B818652A
Hybrid micro-/nano-silica architectures made of bacterial-body-templated silica shell attached with fimbriae-templated silica nanotubes were prepared by using living fimbriaed bacteria E. Coli TG1 as templates, which can function as individual bioreactors to catalyze the hydrolysis of 4-nitrophenyl-β-D-galactopyranoside to form p-nitrophenol due to the presence of an intracellular enzyme.
Co-reporter:Meng Wang, Wei Hou, Cong-Cong Mi, Wen-Xing Wang, Zhang-Run Xu, Hong-Hui Teng, Chuan-Bin Mao and Shu-Kun Xu
Analytical Chemistry 2009 Volume 81(Issue 21) pp:8783
Publication Date(Web):October 6, 2009
DOI:10.1021/ac901808q
Near-infrared (NIR) light can penetrate biological samples and even tissues without causing sample damage and avoid autofluorescence from biological samples in fluorescence detection. Thus, a luminescence resonance energy transfer (LRET)-based immunoassay that can be excited by NIR irradiation is a promising approach to the analysis of biological samples. Here we demonstrate the use of NIR-to-visible upconversion nanoparticles (UCNPs) as an energy donor, which can emit a visible light upon the NIR irradiation, and gold nanoparticles (Au NPs) as an energy acceptor, which can absorb the visible light emitted from the donor, to develop a sandwich-type LRET-based immunoassay for the detection of goat antihuman immunoglobulin G (IgG). Amino-functionalized NaYF4:Yb, Er UCNPs and Au NPs were first prepared and then conjugated with the human IgG and rabbit antigoat IgG, respectively. The NIR-excited fluorescence emission band of human IgG-conjugated NaYF4:Yb, Er UCNPs (λmax = 542 nm) partially overlaps with the visible absorption band of the rabbit antigoat IgG-conjugated colloidal Au NPs (λmax = 530 nm), satisfying the requirement of spectral overlap between donors and acceptors for LRET. A LRET system was then formed when goat antihuman IgG was added to a mixture of human IgG-modified NaYF4:Yb, Er UCNPs (donor) and rabbit antigoat IgG-modified Au NPs (acceptor). The sandwich-type immunoreactions between the added goat antihuman IgG (primary antibody) and the two different proteins (antigen and secondary antibody on the surface of the donors and acceptors, respectively) cross-bridge the donors and acceptors and thus shorten their spacing, leading to the occurrence of LRET from UCNPs to Au NPs upon NIR irradiation. As a result, the quenching of the NIR-excited fluorescence of the UCNPs is linearly correlated to the concentration of the goat antihuman IgG (in the range of 3−67 μg·mL−1) present in the system, enabling the detection and quantification of the antibody. Such sandwich-type LRET-based approach can reach a very low detection limit of goat antihuman IgG (0.88 μg·mL−1), indicating that this method is applicable for the trace protein detection. This approach is expected to be extended to the detection of other biological molecules once the donor and acceptor nanoparticles are modified by proper molecules that can recognize the target biomolecules.
Co-reporter:Pascaline Ngweniform, Dong Li and Chuanbin Mao
Soft Matter 2009 vol. 5(Issue 5) pp:954-956
Publication Date(Web):02 Feb 2009
DOI:10.1039/B817863A
Cationic liposomes loaded with a model drug (zinc phthalocyanine, ZnPc) for photodynamic cancer therapy can be electrostatically assembled on anionic flagellar protein nanotubes that can be displayed with cancer cell-targeting peptides.
Co-reporter:Meng Wang, Congcong Mi, Yixin Zhang, Jinling Liu, Feng Li, Chuanbin Mao and Shukun Xu
The Journal of Physical Chemistry C 2009 Volume 113(Issue 44) pp:19021-19027
Publication Date(Web):October 9, 2009
DOI:10.1021/jp906394z
NaYbF4:RE upconversion (UC) fluorescent nanoparticles (NPs) were synthesized with variable rare-earth dopants (RE = Er3+, Tm3+, or Ho3+, or a combination of these ions) from rare-earth stearate precursors in a water−ethanol−oleic acid system by using a two-phase solvothermal method. The NPs were shown to emit visible light, such as orange, yellow, green, cyan, blue or pink light in response to near-infrared (NIR) irradiation, and their emission colors could be simply tuned by changing either the codopant concentration or the dopant species. The UC NPs were well-dispersed and spherical with an average size of 15−35 nm. They emitted strong UC fluorescence under the 980 nm NIR excitation. The effects of solvothermal reaction time and temperature on nanoparticle size and phase structure as well as UC fluorescence intensity were systematically studied. Water dispersibility was achieved by forming a silica coat on the surface of the UC NPs. After animo functionalization, the silica-coated UC NPs were chemically conjugated with the rabbit anti-CEA8 antibody and then used as fluorescent biolabels for the immunolabeling and imaging of HeLa cells. The NIR-responsive multicolor visible light emission of these UC NPs will enable potential applications in biolabeling and multiplexed analysis because NIR light can penetrate tissue as deep as several inches and is safe to the human body.
Co-reporter:Meng Wang, Cong-Cong Mi, Wen-Xing Wang, Cui-Hong Liu, Ying-Fan Wu, Zhang-Run Xu, Chuan-Bin Mao and Shu-Kun Xu
ACS Nano 2009 Volume 3(Issue 6) pp:1580
Publication Date(Web):May 28, 2009
DOI:10.1021/nn900491j
Upconversion fluorescent nanoparticles can convert a longer wavelength radiation (e.g., near-infrared light) into a shorter wavelength fluorescence (e.g., visible light) and thus have emerged as a new class of fluorescent probes for biomedical imaging. Rare-earth doped β-NaYF4:Yb,Er upconversion nanoparticles (UCNPs) with strong UC fluorescence were synthesized in this work by using a solvothermal approach. The UCNPs were coated with a thin layer of SiO2 to form core−shell nanoparticles via a typical Stöber method, which were further modified with amino groups. After surface functionalization, the rabbit anti-CEA8 antibodies were covalently linked to the UCNPs to form the antibody−UCNP conjugates. The antibody−UCNP conjugates were used as fluorescent biolabels for the detection of carcinoembryonic antigen (CEA), a cancer biomarker expressed on the surface of HeLa cells. The successful conjugation of antibody to the UCNPs was found to lead to the specific attachment of the UCNPs onto the surface of the HeLa cells, which further resulted in the bright green UC fluorescence from the UCNP-labeled cells under 980 nm near-infrared (NIR) excitation and enabled the fluorescent imaging and detection of the HeLa cells. These results indicate that the amino-functionalized UCNPs can be used as fluorescent probes in cell immunolabeling and imaging. Because the UCNPs can be excited with a NIR light to exhibit strong visible fluorescence and the NIR light is safe to the body and can penetrate tissue as deep as several inches, our work suggests that, with proper cell-targeting or tumor-homing peptides or proteins conjugated, the NaYF4:Yb,Er UCNPs can find potential applications in the in vivo imaging, detection, and diagnosis of cancers.Keywords: biolabel; cell imaging; fluorescence; immunolabeling; upconversion
Co-reporter:Binrui Cao and Chuanbin Mao
Biomacromolecules 2009 Volume 10(Issue 3) pp:
Publication Date(Web):February 2, 2009
DOI:10.1021/bm801224q
Microtubule is an important structural and functional component in cells. Microtubule-associated proteins (MAPs) are a class of proteins that can bind to microtubules and stabilize them to maintain their functions. However, not all the specific microtubule-binding domains on MAPs are clear. Here we report the study of microtubule-binding domains on MAPs from a new angle by biopanning a new type of phage-displayed random peptide library (called landscape phage library) against purified α- and β-tubulins. In the landscape phage library, billions of fd-tet phage clones are present and a unique 9-mer peptide is fused to each of the ∼3900 copies of major coat protein (pVIII) in each clone. The affinity-selected peptides derived from the biopanning were analyzed by the receptor ligand contacts (RELIC) suite of programs, which is a bioinformatics tool for combinatorial peptide analysis and identification of protein−ligand interaction sites. By using RELIC, the affinity-selected peptides were shown to have similarity with the sequences of two MAP families (MAP1 and MAP2/tau), thereby identifying putative microtubule-binding domains on these MAPs. The tubulin-binding affinity was also confirmed by using transmission electron microscopy (TEM) to characterize the interaction between affinity-selected tubulin-binding phage and tubulins. Our results confirm some known microtubule-binding domains and identify some new microtubule-binding domains and thus shed light into the mechanism of microtubule−MAPs interactions.
Co-reporter:Chuanbin Mao ;Aihua Liu ;Binrui Cao
Angewandte Chemie International Edition 2009 Volume 48( Issue 37) pp:6790-6810
Publication Date(Web):
DOI:10.1002/anie.200900231
Abstract
Viruses have recently proven useful for the detection of target analytes such as explosives, proteins, bacteria, viruses, spores, and toxins with high selectivity and sensitivity. Bacteriophages (often shortened to phages), viruses that specifically infect bacteria, are currently the most studied viruses, mainly because target-specific nonlytic phages (and the peptides and proteins carried by them) can be identified by using the well-established phage display technique, and lytic phages can specifically break bacteria to release cell-specific marker molecules such as enzymes that can be assayed. In addition, phages have good chemical and thermal stability, and can be conjugated with nanomaterials and immobilized on a transducer surface in an analytical device. This Review focuses on progress made in the use of phages in chemical and biological sensors in combination with traditional analytical techniques. Recent progress in the use of virus–nanomaterial composites and other viruses in sensing applications is also highlighted.
Co-reporter:Chuanbin Mao ;Aihua Liu ;Binrui Cao
Angewandte Chemie 2009 Volume 121( Issue 37) pp:6922-6943
Publication Date(Web):
DOI:10.1002/ange.200900231
Abstract
Viren haben sich in jüngster Zeit als einzigartige Hilfsmittel für den empfindlichen und selektiven Nachweis von Analyten wie Explosivstoffen, Proteinen, Bakterien, Viren, Sporen und Toxinen erwiesen. Auf Bakterien spezialisierte Viren, die Bakteriophagen – oder kurz Phagen –, wurden dabei am intensivsten untersucht: Zielspezifische nichtlysierende Phagen (sowie von diesen präsentierte Peptide und Proteine) können mithilfe hoch entwickelter Phagendisplaytechniken identifiziert werden, und lysierende Phagen können gezielt Bakterien aufbrechen und spezifische Zellmarker wie Enzyme ausschütten, die analysiert werden können. Darüber hinaus sind Phagen chemisch wie thermisch hinreichend stabil, und sie lassen sich mit Molekülen kuppeln und mit Nanomaterialien kombinieren und auf der Oberfläche eines Signalwandlers in einem Analysesystems verankern. Im Mittelpunkt dieses Aufsatzes stehen Fortschritte bei der Verwendung von Phagen in Chemo- und Biosensoren durch Kombination mit etablierten analytischen Techniken. Überdies werden aktuelle Entwicklungen bei der Verwendung von Virus-Nanomaterial-Kompositen und anderen Viren in Sensoranwendungen vorgestellt.
Co-reporter:Penghe Qiu
Journal of Nanoparticle Research 2009 Volume 11( Issue 4) pp:885-894
Publication Date(Web):2009 May
DOI:10.1007/s11051-008-9465-1
We studied the kinetics of the reduction of a gold precursor (HAuCl4) and the effect of the molar ratio (R) of sodium citrate, which was introduced from a seed solution, and the gold precursor on the shape evolution of gold nanomaterials in the presence of preformed 13 nm gold nanoparticles as seeds. The reduction of the gold precursor by sodium citrate was accelerated due to the presence of gold seeds. Nearly single-crystalline gold nanowires were formed at a very low R value (R = 0.16) in the presence of the seeds as a result of the oriented attachment of the growing gold nanoparticles. At a higher R value (R = 0.33), gold nanochains were formed due to the non-oriented attachment of gold nanoparticles. At a much higher R value (R = 1.32), only larger spherical gold nanoparticles grown from the seeds were found. In the absence of gold seeds, no single-crystalline nanowires were formed at the same R value. Our results indicate that the formation of the 1D nanostructures (nanochains and nanowires) at low R values is due to the attachment of gold nanoparticles along one direction, which is driven by the surface energy reduction, nanoparticle attraction, and dipole–dipole interaction between adjacent nanoparticles.
Co-reporter:Fuke Wang;Dong Li
Advanced Functional Materials 2008 Volume 18( Issue 24) pp:4007-4013
Publication Date(Web):
DOI:10.1002/adfm.200800889
Abstract
Bacterial flagellum is a protein nanotube that is helically self-assembled from thousands of a protein subunit called flagellin. The solvent-exposed domain of each flagellin on the flagella is genetically modifiable, in that a foreign peptide can be genetically inserted into this domain, leading to the high-density display of this foreign peptide on the surface of flagella. In this work, wild-type and genetically engineered flagella (inner diameter of ∼2 nm and outer diameter of ∼14 nm) detached from the surface of Salmonella bacterial cells are used as templates to site-specifically form silica sheaths on the flagellar surface, resulting in the formation of double-layered silica/flagella nanotubes. The flagella templates inside the silica/flagella nanotubes can be removed to obtain silica nanotubes by calcining the nanotubes at high temperature (550°C). Further calcination of the silica nanotubes at a higher temperature (800 °C) leads to the formation of a periodic nanohole array along the silica fibers with a center-to-center nanohole spacing of ∼79 nm. It is demonstrated that the double-layered silica-flagella nanotubes can be used for selective CdTe quantum dot uptake into the inner channels or selective Au nanoparticle coating on the outer wall of the nanotubes due to the different chemistry between inner flagellum core (protein) and outer silica wall of the nanotubes. It is also found that flagella displaying different peptides result in different morphologies of the silica nanotubes. This work suggests that the monodisperse diameter and genetically tunable surface chemistry of the flagella can be exploited for the fabrication of silica nanotubes with uniform diameter and controllable morphologies as well as silica nanofibers decorated with periodic nanohole arrays.
Co-reporter:Penghe Qiu, Mingying Yang, Xuewei Qu, Yanyan Huai, Ye Zhu, Chuanbin Mao
Biomaterials (October 2016) Volume 104() pp:138-144
Publication Date(Web):October 2016
DOI:10.1016/j.biomaterials.2016.06.033
Although dendritic nanoparticles have been prepared by many different methods, control over their degree of branching (DB) is still impossible, preventing us from understanding the effect of the DB on the properties of the nanodendrites as cancer therapeutics. Herein, we developed a novel seed-mediated method to prepare gold nanodendrites (AuNDs) in an organic solvent using long chain amines as a structural directing agent. We discovered that the DB could be tuned facilely by simply adjusting synthetic parameters, such as the solvent type, the type and concentration of the long chain amines. We found that DB tuning resulted in dramatic tunability in the optical properties in the near infrared (NIR) range, which led to significantly different performance in the photothermal cancer therapy. Our in vitro and in vivo studies revealed that AuNDs with a higher DB were more efficient in photothermal tumor destruction under a lower wavelength NIR irradiation. In contrast, those with a lower DB performed better in tumor destruction under a higher wavelength NIR irradiation, indicating that AuNDs of even lower DB should have even better photothermal cancer therapy efficiency within the second NIR window. Thus, the tunable optical properties of AuNDs in the NIR range allow us to selectively determine a suitable laser wavelength for the best cancer therapeutic performance.
Co-reporter:Kun Ma, Duo Fu, Dongli Yu, Changhao Cui, Li Wang, Zhaoming Guo, Chuanbin Mao
Biomaterials (March 2017) Volume 121() pp:
Publication Date(Web):March 2017
DOI:10.1016/j.biomaterials.2016.12.033
A Sleeping Beauty (SB) transposon system is made of a transposon plasmid (containing gene encoding a desired functional or therapeutic protein) and a transposase plasmid (encoding an enzyme capable of cutting and pasting the gene into the host cell genome). It is a kind of natural, nonviral gene delivery vehicle, which can achieve efficient genomic insertion, providing long-term transgenic expression. However, before the SB transposon system could play a role in promoting gene expression, it has to be delivered efficiently first across cell membrane and then into cell nuclei. Towards this end, we used a nanoparticle-like lipid-based protocell, a closed bilayer of the neutral lipids with the DNA encapsulated inside, to deliver the SB transposon system to cancer cells. The SB transposon system was amplified in situ inside the protocells by a polymerase chain reaction (PCR) process, realizing more efficient loading and delivery of the target gene. To reach a high transfection efficiency, we introduced two targeting moieties, folic acid (FA) as a cancer cell-targeting motif and Dexamethasone (DEX) as a nuclear localization signaling molecule, into the protocells. As a result, the FA enabled the modified targeting protocells to deliver the DNA into the cancer cells with an increased efficiency and the DEX promoted the DNA to translocate to cell nuclei, eventually leading to the increased chromosome insertion efficiency of the SB transposon. In vivo study strongly suggested that the transfection efficiency of FA-modified protocells in the tumor tissue was much higher than that in other tissues, which was consistent with the in vitro results. Our studies implied that with the targeting ligand modification, the protocells could be utilized as an efficient targeting gene carrier. Since the protocells were made of neutral lipids without cationic charges, the cytotoxicity of protocells was significantly lower than that of traditional cationic gene carriers such as cationic liposomes and polyethylenimine, enabling the protocells to be employed in a wider dosage range in gene therapy. Our work shows that the protocells are a promising gene carrier for future clinical applications.
Co-reporter:Congcong Mi, Yanyan Wang, Jingpu Zhang, Huaiqing Huang, Linru Xu, Shuo Wang, Xuexun Fang, Jin Fang, Chuanbin Mao, Shukun Xu
Journal of Biotechnology (20 May 2011) Volume 153(Issues 3–4) pp:125-132
Publication Date(Web):20 May 2011
DOI:10.1016/j.jbiotec.2011.03.014
Quantum dots (QDs) were prepared in genetically engineered Escherichia coli (E. coli) through the introduction of foreign genes encoding a CdS binding peptide. The CdS QDs were successfully separated from the bacteria through two methods, lysis and freezing–thawing of cells, and purified with an anion-exchange resin. High-resolution transmission electron microscopy, X-ray diffraction, luminescence spectroscopy, and energy dispersive X-ray spectroscopy were applied to characterize the as-prepared CdS QDs. The effects of reactant concentrations, bacteria incubation times, and reaction times on QD growth were systematically investigated. Our work demonstrates that genetically engineered bacteria can be used to synthesize QDs. The biologically synthesized QDs are expected to be more biocompatible probes in bio-labeling and imaging.
Co-reporter:Penghe Qiu ; Christina Jensen ; Njoku Charity ; Rheal Towner
Journal of the American Chemical Society () pp:
Publication Date(Web):November 30, 2010
DOI:10.1021/ja102138a
We report a general method for preparing nanoparticle clusters (NPCs) in an oil-in-water emulsion system mediated by cetyl trimethylammonium bromide (CTAB), where previously only individual nanoparticles were obtained. NPCs of magnetic, metallic, and semiconductor nanoparticles have been prepared to demonstrate the generality of the method. The NPCs were spherical and composed of densely packed individual nanoparticles. The number density of nanoparticles in the oil phase was found to be critical for the formation, morphology, and yield of NPCs. The method developed here is scalable and can produce NPCs in nearly 100% yield at a concentration of 5 mg/mL in water, which is approximately 5 times higher than the highest value reported in the literature. The surface chemistry of NPCs can also be controlled by replacing CTAB with polymers containing different functional groups via a similar procedure. The reproducible production of NPCs with well-defined shapes has allowed us to compare the properties of individual and clustered iron oxide nanoparticles, including magnetization, magnetic moments, and contrast enhancement in magnetic resonance imaging (MRI). We found that, due to their collective properties, NPCs are more responsive to an external magnetic field and can potentially serve as better contrast enhancement agents than individually dispersed magnetic NPs in MRI.
Co-reporter:Yajun Shuai, Shuxu Yang, Chenlin Li, Liangjun Zhu, Chuanbin Mao and Mingying Yang
Journal of Materials Chemistry A 2017 - vol. 5(Issue 21) pp:NaN3954-3954
Publication Date(Web):2017/05/12
DOI:10.1039/C7TB00208D
Silk sericin, a water-soluble glue-like protein, is extensively used as a biomaterial because it is biocompatible, hydrophilic, and biodegradable. In addition, hydroxylapatite-based carriers are functionally efficient for drug or gene delivery due to their biodegradability, biocompatibility, and easy metabolism in vivo. Herein, for the first time, this study used sericin, from a wild silkworm called Antheraea pernyi (A. pernyi), as a template to nucleate hydroxylapatite (HAp) nanoneedles and form porous sericin–HAp nanocomposite microspheres as an anticancer drug carrier. Specifically, A. pernyi sericin (AS) was incubated in 1.5× simulated body fluid to induce the formation of porous AS/HAp microspheres in situ. Doxorubicin (DOX) loading and release assays proved that the microspheres exhibited pH-dependent controlled and sustained release of DOX. In particular, the microspheres can selectively release DOX at a higher rate at the acidic conditions typical for tumor microenvironment than at the physiological conditions typical for normal tissues, which will potentially reduce the side effects of the cancer drugs in normal tissues. Cancer cell toxicity assay, cancer cell imaging, and intracellular DOX distribution assay provided further evidence to support the pH-dependent controlled and sustained release of DOX to cancer cells from the microspheres. Our work has demonstrated a biomimetic strategy for the design and synthesis of silk protein-based drug carriers that can be potentially employed in drug delivery and regenerative medicine.
Co-reporter:Jing Chen, Changrun Guo, Meng Wang, Lei Huang, Liping Wang, Congcong Mi, Jing Li, Xuexun Fang, Chuanbin Mao and Shukun Xu
Journal of Materials Chemistry A 2011 - vol. 21(Issue 8) pp:NaN2638-2638
Publication Date(Web):2011/01/06
DOI:10.1039/C0JM02854A
β-NaYF4:Yb,Er upconversion nanoparticles (UCNPs) can emit bright green fluorescence under near-infrared (NIR) light excitation which is safe to the body and can penetrate deeply into tissues. The application of UCNPs in biolabeling and imaging has received great attention recently. In this work, β-NaYF4:Yb,Er UCNPs with an average size of 35 nm, uniformly spherical shape, and surface modified with amino groups were synthesized by a one-step green solvothermal approach through the use of room-temperature ionic liquids as the reactant, co-solvent and template. The as-prepared UCNPs were introduced into Caenorhabditis elegans (C. elegans) to achieve successful in vivo imaging. We found that longer incubation time, higher UCNP concentration and smaller UCNP size can make the in vivo fluorescence of C. elegans much brighter and more continuous along their body. The worms have no apparent selectivity on ingestion of the UCNPs capped with different capping ligands while having similar size and shape. The next generation of worms did not show fluorescence under excitation. In addition, low toxicity of the nanoparticles was demonstrated by investigating the survival rates of the worms in the presence of the UCNPs. Our work demonstrates the potential application of the UCNPs in studying the biological behavior of organisms, and lays the foundation for further development of the UCNPs in the detection and diagnosis of diseases.
Co-reporter:Lijing Hao, Hui Yang, Chang Du, Xiaoling Fu, Naru Zhao, Suju Xu, Fuzhai Cui, Chuanbin Mao and Yingjun Wang
Journal of Materials Chemistry A 2014 - vol. 2(Issue 30) pp:NaN4801-4801
Publication Date(Web):2014/06/27
DOI:10.1039/C4TB00597J
Self-assembled monolayers (SAMs) of alkanethiols on gold have been employed as model substrates to investigate the effects of surface chemistry on cell behavior. However, few studies were dedicated to substrates with controlled wettability in studying the stem cell fate. Here, mixed hydroxyl (–OH) and methyl (–CH3) terminated SAMs were prepared to form substrates with varying wettability, which were used to study the effects of wettability on the adhesion, spreading, proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) from human and mouse origins. The numbers of adhered human fetal MSCs (hMSCs) and mouse bone marrow MSCs (mMSCs) were maximized on –OH/–CH3 mixed SAMs with water contact angles of 40–70° and 70–90°, respectively. Hydrophilic mixed SAMs with a water contact angle of 20–70° also promoted the spreading of both hMSCs and mMSCs. Proliferation of both hMSCs and mMSCs was most favored on hydrophilic SAMs with a water contact angle around 70°. In addition, a moderate hydrophilic surface (with a contact angle of 40–90° for hMSCs and 70° for mMSCs) promoted osteogenic differentiation in the presence of biological stimuli. Hydrophilic mixed SAMs with a moderate wettability tended to promote the expression of αvβ1 integrin of MSCs, indicating that the tunable wettability of the mixed SAMs may guide osteogenesis through mediating the αvβ1 integrin signaling pathway. Our work can direct the design of biomaterials with controllable wettability to promote the adhesion, proliferation and differentiation of MSCs from different sources.
Co-reporter:Wei Xie, Penghe Qiu and Chuanbin Mao
Journal of Materials Chemistry A 2011 - vol. 21(Issue 14) pp:NaN5202-5202
Publication Date(Web):2011/01/11
DOI:10.1039/C0JM03301D
Surface-enhanced Raman scattering (SERS) is a phenomenon that occurs on nanoscale-roughed metallic surface. The magnitude of the Raman scattering signal can be greatly enhanced when the scatterer is placed in the very close vicinity of the surface, which enables this phenomenon to be a highly sensitive analytical technique. SERS inherits the general strongpoint of conventional Raman spectroscopy and overcomes the inherently small cross section problem of a Raman scattering. It is a sensitive and nondestructive spectroscopic method for biological samples, and can be exploited either for the delivery of molecular structural information or for the detection of trace levels of analytes. Therefore, SERS has long been regarded as a powerful tool in biomedical research. Metallic nanostructure plays a key role in all the biomedical applications of SERS because the enhanced Raman signal can only be obtained on the surface of a finely divided substrate. This review focuses on progress made in the use of SERS as an analytical technique in bio-imaging, analysis and detection. Recent progress in the fabrication of SERS active nanostructures is also highlighted.
Co-reporter:Xiang Li, Qiuhong Zhang, Zeeshan Ahmad, Jie Huang, Zhaohui Ren, Wenjian Weng, Gaorong Han and Chuanbin Mao
Journal of Materials Chemistry A 2015 - vol. 3(Issue 37) pp:NaN7456-7456
Publication Date(Web):2015/08/28
DOI:10.1039/C5TB01158B
750–850 nm (NIR I) and 1000–1400 nm (NIR II) in the near infrared (NIR) spectra are two windows of optical transparency for biological tissues with the latter capable of penetrating tissue deeper. Monitoring drug release from the drug carrier is still a daunting challenge in the field of nanomedicine. To overcome such a challenge, we propose to use porous Nd3+-doped CaTiO3 nanofibers, which can be excited by NIR I to emit NIR II light, to carry drugs to test the concept of monitoring drug release from the nanofibers by detecting the NIR II emission intensity. Towards this end, we first used electrospinning to prepare porous Nd3+-doped CaTiO3 nanofibers by adding micelle-forming surfactant Pluronic F127, followed by annealing to remove the organic component. After a model drug, ibuprofen, was loaded into the porous nanofibers, the drug release from the nanofibers into the phosphate buffered saline (PBS) solution was monitored by detecting the NIR II emission from the nanofibers. We found that the release of the drug molecules from the nanofibers into the PBS solution triggers the quenching of NIR II emission by the hydroxyl groups in the surrounding media. Consequently, more drug release corresponded to more reduction in the intensity of the NIR II emission, allowing us to monitor the drug release by simply detecting the intensity of NIR II from the nanofibers. In addition, we demonstrated that tuning the amount of micelle-forming surfactant Pluronic F127 enabled us to tune the porosity of the nanofibers and thus the drug release kinetics. This study suggests that Nd3+ doped CaTiO3 nanostructures can serve as a promising drug delivery platform with the potential to monitor drug release kinetics by detecting the tissue-penetrating NIR emission.
Co-reporter:Dong Li, Xuewei Qu, Salete M. C. Newton, Philip E. Klebba and Chuanbin Mao
Journal of Materials Chemistry A 2012 - vol. 22(Issue 31) pp:NaN15709-15709
Publication Date(Web):2012/05/21
DOI:10.1039/C2JM31034A
Bacterial flagella are naturally occurring self-assembling protein nanofibers protruding from the bacterial surface to assist the swimming of bacteria. They are rigid and exhibit diverse morphologies depending on the ionic strength, the pH values, temperature, and subunit sequences. Here, silica nanotubes (SNTs) with controllable morphologies were synthesized using flagella as biological templates in aqueous solution under mild conditions. The morphologies and surface features of flagella-templated SNTs can be simply tuned by adjusting the pH value or surface chemistry of flagella by peptide display. A variety of different morphologies (coiled, straight, and curly with different wavelengths) and surface features (smooth, rough, granular and pearl-necklace-like) of SNTs were obtained. When pH varies from acidic to alkaline conditions, in general, SNTs varied from bundled coiled, to characteristic sinusoidal waves, helical, and straight morphologies. Under genetic control, flagella displaying negatively charged peptides exhibited thinner layer of silica condensation but a rougher surface. However, flagella with positively charged peptide inserts induced the deposition of a thicker silica shell with a smoother surface. Incorporation of hydroxyl bearing amino acid residues such as Ser into the peptide displayed on flagella highly enhanced the biotemplated deposition of silica. This work suggests that bacterial flagella are promising biotemplates for developing an environmentally benign and cost-efficient approach to morphology-controlled synthesis of nanotubes. Moreover, the dependency of the thickness of the silica shell on the peptides displayed on flagella helps us to further understand the mechanism of biomimetic nucleation of silica on biological templates.
Co-reporter:Dong Li, Ye Zhu and Chuanbin Mao
Journal of Materials Chemistry A 2013 - vol. 1(Issue 40) pp:NaN5520-5520
Publication Date(Web):2013/09/09
DOI:10.1039/C3TB20733A
A green one-pot approach is used to synthesize surface morphology controlled hollow silica spheres in aqueous solution under ambient conditions. Using cationic polystyrene particles as templates and aminopropyltriethoxysilane (APTES) as a structure directing agent, the surface roughness and wall thickness could be easily controlled by varying the concentration of tetraethoxysilane (TEOS). The smooth surface of hollow silica spheres with different wall thicknesses was obtained using anionic polystyrene particles. The resulting hollow silica spheres with a rough surface had better performance in carrying and releasing a model drug.
Co-reporter:Fuke Wang and Chuanbin Mao
Chemical Communications 2009(Issue 10) pp:NaN1224-1224
Publication Date(Web):2009/01/13
DOI:10.1039/B818652A
Hybrid micro-/nano-silica architectures made of bacterial-body-templated silica shell attached with fimbriae-templated silica nanotubes were prepared by using living fimbriaed bacteria E. Coli TG1 as templates, which can function as individual bioreactors to catalyze the hydrolysis of 4-nitrophenyl-β-D-galactopyranoside to form p-nitrophenol due to the presence of an intracellular enzyme.
Co-reporter:Lihua Li, Mei Li, Dan Li, Peng He, Hong Xia, Yu Zhang and Chuanbin Mao
Journal of Materials Chemistry A 2014 - vol. 2(Issue 36) pp:NaN5961-5961
Publication Date(Web):2014/07/28
DOI:10.1039/C4TB00666F
A great challenge in orthopedic tumor operation faced by orthopedic implants is the high recurrence and metastasis of bone tumor as well as the bacterial infection associated with the implants. Thus ideal titanium (Ti)-based bone implants should be able to not only inhibit cancer cell adhesion and proliferation, and promote cancer cell apoptosis, but also resist bacterial infections. Towards this end, we developed a new approach to modify the surface of Ti-based bone implants so that they can restrain functions of osteoclastoma (giant cell tumor of bone) cancer cells (GCTs) and inhibit the adhesion of bacteria. First, the surface of pristine Ti substrates was functionalized with dopamine (DA) to form DA–Ti substrates. Then nanoparticles electrostatically assembled from poly-lysine (PLL) and heparin (Hep) were chemically immobilized onto the DA–Ti substrates to form PLL/Hep–Ti substrates. Chitosan (CH) and methotrexate (MTX) were then electrostatically immobilized onto the PLL/Hep–Ti substrates to generate CH–MTX–Ti substrates. The successful functionalization of the Ti substrates was confirmed by X-ray photoelectron spectroscopy. GCTs cultured on differently functionalized Ti substrates were investigated in terms of cell adhesion, cytoskeleton, proliferation, cytotoxicity and apoptosis. The growth of Staphylococcus aureus bacteria in the presence of different substrates was also assayed. Our results showed that CH–MTX–Ti substrates not only significantly inhibited the adhesion, proliferation and viability of GCTs, and promoted the apoptosis of GCTs, but also prevented the adhesion of the bacteria and the subsequent formation of bacterial biofilms, when compared to other Ti substrates. Thus CH–MTX–Ti substrates are expected to be used as orthopedic prostheses in bone tumor surgery that can inhibit both osteoclastoma formation and bacterial infection.
Co-reporter:Jingwen Liao, Ye Zhu, Zhaoyi Yin, Guoxin Tan, Chengyun Ning and Chuanbin Mao
Journal of Materials Chemistry A 2014 - vol. 2(Issue 45) pp:NaN7876-7876
Publication Date(Web):2014/10/21
DOI:10.1039/C4TB01053A
Citric acid, a molecule present in fresh bone, was introduced into template-free electrochemical polymerization to form biocompatible coating made of polypyrrole (PPy) nano-cones on bone implants. It served not only as a dopant to tune the nano-architectures but also as a promoter to enhance bioactivity of the PPy-coated implants.
Co-reporter:Binrui Cao, Mingying Yang, Lin Wang, Hong Xu, Ye Zhu and Chuanbin Mao
Journal of Materials Chemistry A 2015 - vol. 3(Issue 39) pp:NaN7672-7672
Publication Date(Web):2015/09/03
DOI:10.1039/C5TB01509J
Synthetic nanoparticles are always terminated with coating molecules, which are often cytotoxic and not desired in biomedicine. Here we propose a novel reaction-dissolution approach to remove the cytotoxic coating molecules. A two-component solution is added to the nanoparticle solution; one component reacts with the coating molecules to form a salt whereas another is a solvent for dissolving and thus removing the salt. As a proof of concept, this work uses a NaOH–ethanol solution to remove the cytotoxic linoleic acid molecules coated on the hydroxyapatite nanorods (HAP-NRs). The removal of the coating molecules not only significantly improves the biocompatibility of HAP-NRs but also enables their oriented attachment into tightly-bound superstructures, which mimic the organized HAP crystals in bone and enamel and can promote the osteogenic differentiation of mesenchymal stem cells. Our reaction-dissolution approach can be extended to the surface “cleaning” of other nanomaterials.
Co-reporter:Alessandro Polini, Jianglin Wang, Hao Bai, Ye Zhu, Antoni P. Tomsia and Chuanbin Mao
Biomaterials Science (2013-Present) 2014 - vol. 2(Issue 12) pp:NaN1786-1786
Publication Date(Web):2014/08/07
DOI:10.1039/C4BM00164H
Hydroxyapatite (HA), the principal component of bone mineral, shows osteoconductive properties when employed for coating metal implants as well as scaffold materials in synthetic bone grafts. With the goal of providing this material with osteoinductive capabilities to promote faster bone regeneration, we show an easy approach to functionalize HA implant surfaces and enrich them with osteoinductive properties by the use of HA-binding modular peptides. The modular peptides are designed as a combination of two domains, an HA-binding peptide motif and an osteogenic peptide motif derived from the osteogenic growth peptide (OGP) or bone morphometric protein 7 (BMP-7). To identify the best HA-binding peptide, several nature-inspired peptides derived from natural bone extracellular matrix proteins (bone sialoprotein, osteonectin, osteocalcin, and salivarin statherin) were compared for HA-binding activity, revealing concentration-dependent and incubation-time-dependent behaviours. We discovered that a Poly-E heptamer (E7) is the best HA-binding peptide, and thus combined it with a second osteogenic peptidic domain to create an osteoinductive modular peptide. After binding/release characterization, we found that the addition of the second osteogenic peptide domain did not change the binding profile of the modular peptides and caused only a slight change in their release kinetics. Mesenchymal stem cells (MSCs) were cultured on the HA substrates functionalized with modular peptides, and cell adhesion, proliferation, and differentiation in a basal medium (i.e., without any osteogenic supplements) were investigated. Gene expression data clearly showed that MSCs were committed to differentiate into osteoblasts in the presence of the modular peptides. HA discs functionalized with the E7 BMP-7 modular peptide showed the best capability in inducing the osteogenic differentiation of MSCs among all modular peptides studied. The modular peptides can easily be used to functionalize the HA implants through its constituent HA-binding motif, leaving the osteogenic peptide motif protruding from the surface for inducing osteogenesis. Our work opens up a new approach to the formulation of new bioactive HA coatings and implants for bone and dental repair.
Co-reporter:Guanping He, Yuanhao Wu, Yu Zhang, Ye Zhu, Yang Liu, Nan Li, Mei Li, Guan Zheng, Baohua He, Qingshui Yin, Yufeng Zheng and Chuanbin Mao
Journal of Materials Chemistry A 2015 - vol. 3(Issue 32) pp:NaN6689-6689
Publication Date(Web):2015/07/27
DOI:10.1039/C5TB01319D
Most of the magnesium (Mg) alloys possess excellent biocompatibility, mechanical properties and biodegradability in orthopedic applications. However, these alloys may suffer from bacterial infections due to their insufficient antibacterial capability. In order to reduce the post-surgical infections, a series of biocompatible Mg–1Ca–0.5Sr–xZn (x = 0, 2, 4, 6) alloys were fabricated with the addition of antibacterial Zn with variable contents and evaluated in terms of their biocompatibility and antibacterial properties. The in vitro corrosion study showed that Mg–1Ca–0.5Sr–6Zn alloys exhibited a higher hydrogen evolution volume after 100 h immersion and resulted in a higher pH value of the immersion solution. Our work indicated that Zn-containing Mg alloys exhibited good biocompatibility with high cell viability. The antibacterial studies reveal that the number of bacteria adhered on all of these Mg alloy samples diminished remarkably compared to the Ti–6Al–4V control group. We also found that the proliferation of the bacteria was inhibited by these Mg alloy extracts. Among the prepared alloys, the Mg–1Ca–0.5Sr–6Zn alloy not only exhibited a strong antibacterial effect, but also promoted the proliferation of MC3T3-E1 osteoblasts, suggesting that it is a promising alloy with both good antibacterial properties and good biocompatibility for use as an orthopedic implant.
Co-reporter:Mingying Yang, Guanshan Zhou, Yajun Shuai, Jie Wang, Liangjun Zhu and Chuanbin Mao
Journal of Materials Chemistry A 2015 - vol. 3(Issue 12) pp:NaN2462-2462
Publication Date(Web):2015/02/17
DOI:10.1039/C4TB01944J
Bone biomineralization is a well-regulated protein-mediated process where hydroxylapatite (HAP) crystals are nucleated with preferred orientation within the self-assembled protein matrix. Mimicking this process is a promising approach to the production of bone-like protein/mineral nanocomposites for bone repair and regeneration. Towards the goal of fabricating such nanocomposites from sericin, a protein spun by Bombyx mori (B. mori) silkworm, and bone mineral HAP, for the first time we investigated the chemical mechanism underpinning the synergistic processes of the conformational change/self-assembly of B. mori sericin (BS) as well as the nucleation of HAP on the resultant self-assembled BS matrix. We found that BS, rich in anionic amino acid residues, could bind Ca2+ ions from the HAP precursor solution through electrostatic attraction. The Ca2+ binding drove the conformational change of BS from random coils into β-sheets and its concomitant self-assembly into the interconnected nanofibrous network-like protein matrix, which initiated the nucleation and growth of HAP crystals. HAP crystals directed by the resultant self-assembled BS matrix grew preferentially along their crystallographic c-axis, leading to the formation of HAP nano-needles. The HAP nano-needles in the self-assembled BS matrix were subsequently aggregated into globules, probably driven by the hydrogen bonding between CO groups of BS and O–H groups of HAP nano-needles. The present work sheds light on the chemical mechanisms of BS self-assembly and the controlled mineralization directed by the self-assembled matrix. We also found that the resultant nanocomposites could promote the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. Thus our work also generates a biomimetic approach to bone-like silk protein/mineral nanocomposite scaffolds that can find potential applications in bone repair and regeneration.
Co-reporter:Fuke Wang, Susan L. Nimmo, Binrui Cao and Chuanbin Mao
Chemical Science (2010-Present) 2012 - vol. 3(Issue 8) pp:NaN2645-2645
Publication Date(Web):2012/05/15
DOI:10.1039/C2SC00583B
Biomimetic silica formation is strongly dependent on the presence of cationic amine groups which hydrolyze organosilicate precursors and bind to silicate oligomers. Since most biological species possess anionic surfaces, the dependence on amine groups limits utilization of biotemplates for fabricating materials with specific morphologies and pore structures. Here, we report a general aminopropyltriethoxysilane (APTES) directed method for preparing hollow silica with well-defined morphologies using varying biotemplates (proteins, viruses, flagella, bacteria and fungi). Control experiments, pH evolution measurements and 29Si NMR spectroscopic studies have revealed a mechanism of the assembly of APTES on bio-surfaces with subsequent nucleation and growth of silica. The APTES assembly and nuclei formation on bio-surfaces ensured precise transcription of the morphologies of biotemplates to the resulting silica. This method could be extended to the preparation of other oxides.