Qian Wang

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Name: Wang, Qian

Organization: University of South Carolina , USA

Department: Department of Chemistry and Biochemistry

Title: Professor(PhD)

TOPICS

Polymer

Dendrimers Polyesters

Chemicals
References

Effect of Roughness on in Situ Biomineralized CaP-Collagen Coating on the Osteogenesis of Mesenchymal Stem Cells

Co-reporter:Sheng Feng;Xingjie Zan;Pongkwan Sitasuwan

Langmuir February 23, 2016 Volume 32(Issue 7) pp:1808-1817

Publication Date(Web):2017-2-22

DOI:10.1021/acs.langmuir.5b04245

Because of its outstanding osteo-conductive property, a calcium phosphate (CaP) coating has been used as an implant coating for bone tissue engineering. Nevertheless, the issues, such as harsh fabrication conditions, long-term stability and biocompatibility, and the requirement for expensive instruments, still exist in current coating techniques. To address these issues, the CaP coatings doped with collagen (CaP-Col) were in situ generated on polyelectrolyte multilayers (PEMs) by incubating PEMs in a mixture of the collagen, phosphate, and calcium ions. The resulting coatings have controllable physical properties (chemical composition, crystallinity, and roughness) and good stability before and after incubation with cell culture medium. We also found that both the cellular viability and osteogenesis of mesenchymal stem cells (MSCs) were closely related to the roughness of PEMs/CaP-Col, one of the easily ignored physical factors in current coating designs but very critical. The existed roughness window (between 18 ± 1.2 and 187 ± 7.3 nm) suitable for MSC proliferation on PEMs/CaP-Col coating and the optimal roughness (∼98 ± 3.5 nm) for MSC osteogenesis further demonstrated that the roughness was a critical factor for bone formation. Therefore, we envision that our exploration of the effects of surface roughness on MSC behaviors would provide better guidance for the future design of material coating and eventual medical success.

Polymer–Protein Core–Shell Nanoparticles for Enhanced Antigen Immunogenicity

Co-reporter:Xiaolei Zhang, Xia Zhao, Jittima Amie Luckanagul, Jing Yan, Yuzhe Nie, L. Andrew Lee, and Qian Wang

ACS Macro Letters April 18, 2017 Volume 6(Issue 4) pp:442-442

Publication Date(Web):April 3, 2017

DOI:10.1021/acsmacrolett.7b00049

Nanoengineered vaccine platforms can be modeled after viruses and other pathogens with highly organized and repetitive structures that trigger the host immune system. Here we demonstrated a pyridine-grafted poly(ε-caprolactone)-based polymer–protein core–shell nanoparticles (PPCS-NPs) platform can effectively trigger the host immune system and lead to significantly higher antibody titers.

Experimental Investigations on Fluorescence Excitation and Depletion of Carbon Dots

Co-reporter:Yunxia Wang;Zhenhua Bai;Guiren Wang

Journal of Fluorescence 2017 Volume 27( Issue 4) pp:1435-1441

Publication Date(Web):18 April 2017

DOI:10.1007/s10895-017-2082-6

Carbon dots (CDs) can be readily synthesized and utilized as attractive fluorescent probes for a variety of applications. In this study, we have synthesized CDs using a previously published method and characterized their photo-physical properties. The resultant CDs possess prominent photo-stability and short emission wavelength in the violet region. Our study reveals that CDs, with weak photo-bleaching, enable them to be employed to achieve high spatial resolution in stimulated emission depletion (STED) microscopy. The depletion efficiency can reach 60%. More importantly, the shorter excitation wavelength of CDs contributes to further improvement of resolution for STED microscopy. An excellent candidate for fluorophores, these CDs have potential to be used in super-resolution imaging for STED microscopy.

Influence of Cross-Linkers on the in Vitro Chondrogenesis of Mesenchymal Stem Cells in Hyaluronic Acid Hydrogels

Co-reporter:Panita Maturavongsadit, Xiangdong Bi, Kamolrat Metavarayuth, Jittima Amie Luckanagul, and Qian Wang

ACS Applied Materials & Interfaces 2017 Volume 9(Issue 4) pp:

Publication Date(Web):December 27, 2016

DOI:10.1021/acsami.6b12437

This study aims to investigate the effect of the structures of cross-linkers on the in vitro chondrogenic differentiation of bone mesenchymal stem cells (BMSCs) in hyaluronic acid (HA)-based hydrogels. The hydrogels were prepared by the covalent cross-linking of methacrylated HA with different types of thiol-tailored molecules, including dithiothreitol (DTT), 4-arm poly(ethylene glycol) (PEG), and multiarm polyamidoamine (PAMAM) dendrimer using thiol–ene “click” chemistry. The microstructure, mechanical properties, diffusivity, and degradation rates of the resultant hydrogels were controlled by the structural feature of different cross-linkers. BMSCs were then encapsulated in the resulting hydrogels and cultured in chondrogenic conditions. Overall, chondrogenic differentiation was highly enhanced in the PEG-cross-linked HA hydrogels, as measured by glycosaminoglycan (GAG) and collagen accumulation. The physical properties of hydrogels, especially the mechanical property and microarchitecture, were resulted from the structures of different cross-linkers, which subsequently modulated the fate of BMSC differentiation.Keywords: chondrogenesis; dithiothreitol; hyaluronic acid; mesenchymal stem cells; PAMAM dendrimer; poly(ethylene glycol);

Novel H2S Releasing Nanofibrous Coating for In Vivo Dermal Wound Regeneration

Co-reporter:Jiang Wu, Yi Li, Chaochao He, Jianming Kang, Jingjing Ye, Zecong Xiao, Jingjing Zhu, Anqi Chen, Sheng Feng, Xiaokun Li, Jian Xiao, Ming Xian, and Qian Wang

ACS Applied Materials & Interfaces 2016 Volume 8(Issue 41) pp:27474

Publication Date(Web):August 9, 2016

DOI:10.1021/acsami.6b06466

Hydrogen sulfide (H2S), together with nitric oxide and carbon monoxide, has been recognized as an important gasotransmitter. It plays an essential physiological role in regulating cyto-protective signal process, and H2S-based therapy is considered as the next generation of promising therapeutic strategies for many biomedical applications, such as the treatment of cardiovascular disease. Through electrospinning of polycaprolactone (PCL) containing JK1, a novel pH-controllable H2S donor, nanofibers with H2S releasing function, PCL-JK1, are fabricated. This fibrous scaffold showed a pH-dependent H2S releasing behavior, i.e., lower pH induced greater and faster H2S release. In addition, the H2S release of JK1 was prolonged by the fibrous matrix as shown by decreased releasing rates compared to JK1 in solutions. In addition, in vitro studies indicated that PCL-JK1 exhibited excellent cyto-compatibility, similar to PCL fibers. Finally, we investigated PCL-JK1 as a wound dressing toward a cutaneous wound model in vivo and found that PCL-JK1 could significantly enhance the wound repair and regeneration compared with the control PCL scaffold, likely due to the release of H2S, which results in a broad range of physiologically protective functions toward the wound.Keywords: controlled release; electrospinning; fibrous materials; hydrogen sulfide; polycaprolactone; wound healing

Adhesive peptides conjugated PAMAM dendrimer as a coating polymeric material enhancing cell responses

Co-reporter:Panita Maturavongsadit, Xiangdong Bi, Togor A. Gado, Yu-Zhe Nie, Qian Wang

Chinese Chemical Letters 2016 Volume 27(Issue 9) pp:1473-1478

Publication Date(Web):September 2016

DOI:10.1016/j.cclet.2016.03.012

This present work aims to functionalize poly(amidoamine) (PAMAM) dendrimers with various reported adhesive peptides, including Arg-Gly-Asp (RGD), Tyr-Ile-Gly-Ser-Arg (YIGSR), and Ile-Lys-Val-Ala-Val (IKVAV) for enhancing cell responses. The RGD, YIGSR, or IKVAV functionalized PAMAM coated substrate could promote cell adhesion of bone marrow mesenchymal stem cells (BMSCs) within 1 h after incubation. The neurite differentiation and proliferation of pheochromocytoma (PC12) cells were also significantly enhanced after culturing on the peptide functionalized PAMAM dendrimers for two and four days. This peptide functionalized PAMAM dendrimers are considered as the potential candidates for various tissue engineering applications.This present work aims to functionalize poly(amidoamine) (PAMAM) dendrimers with various reported adhesive peptides, including Arg-Gly-Asp (RGD), Tyr-Ile-Gly-Ser-Arg (YIGSR), and Ile-Lys-Val-Ala-Val (IKVAV) for enhancing cell responses.

Tobacco Mosaic Virus Functionalized Alginate Hydrogel Scaffolds for Bone Regeneration in Rats with Cranial Defect

Co-reporter:Jittima Amie Luckanagul, Kamolrat Metavarayuth, Sheng Feng, Phudit Maneesaay, Amy Y. Clark, Xiaoming Yang, Andrés J. García, and Qian Wang

ACS Biomaterials Science & Engineering 2016 Volume 2(Issue 4) pp:606

Publication Date(Web):March 4, 2016

DOI:10.1021/acsbiomaterials.5b00561

Plant viruses have been highlighted among material research due to their well-defined structures in nanoscale, monodispersity, stability, and chemical functionalities. Each of the thousands coat protein subunits on a viral nanoparticle can be homogeneously modified, chemically and genetically, with a functional ligand leading to a high-density and spatial distribution of ligands on each particle (multivalency). Previous reports from our group have evidenced that substrates coated with Tobacco mosaic virus (TMV) and its mutant promote early osteogenesis of mesenchymal stem cells (MSCs). We then fabricated a three-dimensional (3D) biopolymeric scaffold with rod-like TMV in the form of a sponge-like hydrogel for tissue engineering purposes. The hydrogel was functionalized with the cellular recognition peptide, arginine–glycine–aspartic acid (RGD), through an incorporation of an RGD mutant of TMV (TMV-RGD). The virus-functionalized hydrogel materials were shown to aid bone differentiation of MSCs in vitro. Herein, we performed an in vivo study based on the TMV and TMV-RGD hydrogels in Sprague–Dawley rats with cranial bone defects. This report substantiated the hypothesis that TMV-functionalized hydrogel scaffolds did not cause systemic toxicity when implanted in the defect site and that the TMV-based hydrogel platform can support cell localization and can be further optimized for bone regeneration and repair.Keywords: bone regeneration; cranial defect; hydrogel; implant; Tobacco mosaic virus; virus nanoparticles

Influence of Surface Topographical Cues on the Differentiation of Mesenchymal Stem Cells in Vitro

Co-reporter:Kamolrat Metavarayuth, Pongkwan Sitasuwan, Xia Zhao, Yuan Lin, and Qian Wang

ACS Biomaterials Science & Engineering 2016 Volume 2(Issue 2) pp:142

Publication Date(Web):December 23, 2015

DOI:10.1021/acsbiomaterials.5b00377

Adult stem cell research has been advanced in recent years because of the cells’ attractive abilities of self-renewal and differentiation. Topography of materials is one of the key features that can be harnessed to regulate stem cell behaviors. Stem cells can interact with underlying material through nanosized integrin receptors. Therefore, the manipulation of topographical cues at a nanoscale level can be employed to modulate the cell fate. In this review, we focus our discussion on the different surface topographical cues, especially, with an emphasis on the viral nanoparticle-coated materials, and their effects on stem cell differentiation.Keywords: biomaterials; differentiation; plant virus; stem cells; topography

Promotion of In Vitro Chondrogenesis of Mesenchymal Stem Cells Using In Situ Hyaluronic Hydrogel Functionalized with Rod-Like Viral Nanoparticles

Co-reporter:Panita Maturavongsadit, Jittima Amie Luckanagul, Kamolrat Metavarayuth, Xia Zhao, Limin Chen, Yuan Lin, and Qian Wang

Biomacromolecules 2016 Volume 17(Issue 6) pp:

Publication Date(Web):March 21, 2016

DOI:10.1021/acs.biomac.5b01577

This study focuses on the development of injectable hydrogels to mimic the cartilage microenvironment using hyaluronic acid (HA) derivatives as starting materials. Cysteine-inserted Tobacco mosaic virus (TMV) mutants (TMV1cys) could be cross-linked to methacrylated hyaluronic acid (MeHA) polymers by thiol–ene “click” chemistry and form hydrogels under physiological condition. The resulting hydrogels could promote in vitro chondrogenesis of bone marrow mesenchymal stem cells (BMSCs) significantly higher than that in the TMV-free HA hydrogels by upregulating bone morphogenetic protein-2 (BMP-2) expression and enhancing collagen accumulation.

Virus-templated FRET platform for the rational design of ratiometric fluorescent nanosensors

Co-reporter:Limin Chen, Yehong Wu, Yuan Lin and Qian Wang

Chemical Communications 2015 vol. 51(Issue 50) pp:10190-10193

Publication Date(Web):14 May 2015

DOI:10.1039/C5CC02866C

We report here the construction of a bacteriophage M13-templated supramolecular nanosystem, i.e. M13-β-CD/Ada-FITC/Ada-RhB, which can be used as effective ratiometric fluorescent sensors for intracellular sensing.

Virus Nanoparticles Mediated Osteogenic Differentiation of Bone Derived Mesenchymal Stem Cells

Co-reporter:Kamolrat Metavarayuth;Pongkwan Sitasuwan;Jittima Amie Luckanagul;Sheng Feng

Advanced Science 2015 Volume 2( Issue 10) pp:

Publication Date(Web):

DOI:10.1002/advs.201500026

There are few methodologies that allow manipulating a biomaterial surface at nanometer scale, which controllably influence different cellular functions. In this study, virus nanoparticles with different structural features are selected to prepare 2D substrates with defined nanoscale topographies and the cellular responses are investigated. It is demonstrated that the viral nanoparticle based substrates could accelerate and enhance osteogenesis of bone derived mesenchymal stem cells as indicated by the upregulation of osteogenic markers, including bone morphogenetic protein-2, osteocalcin, and osteopontin, at both gene and protein expression levels. Moreover, alkaline phosphatase activity and calcium mineralization, both indicators for a successful bone formation, are also increased in cells grown on these nanoscale possessed substrates. These discoveries and developments present a new paradigm for nanoscale engineering of a biomaterial surface.

Biological thiols-triggered hydrogen sulfide releasing microfibers for tissue engineering applications

Co-reporter:Sheng Feng, Yu Zhao, Ming Xian, Qian Wang

Acta Biomaterialia 2015 Volume 27() pp:205-213

Publication Date(Web):November 2015

DOI:10.1016/j.actbio.2015.09.010

Abstract

By electrospinning of polycaprolactone (PCL) solutions containing N-(benzoylthio)benzamide (NSHD1), a H₂S donor, fibrous scaffolds with hydrogen sulfide (H₂S) releasing capability (H₂S-fibers) are fabricated. The resultant microfibers are capable of releasing H₂S upon immersion in aqueous solution containing biological thiols under physiological conditions. The H₂S release peaks of H₂S-fibers appeared at 2–4 h, while the peak of donor alone showed at 45 min. H₂S release half-lives of H₂S-fibers were 10–20 times longer than that of donor alone. Furthermore, H₂S-fibers can protect cells from H₂O₂ induced oxidative damage by significantly decreasing the production of intracellular reactive oxygen species (ROS). Finally, we investigated the H₂S-fibers application as a wound dressing in vitro. Given that H₂S has a broad range of physiological functions, H₂S-fibers hold great potential for various biomedical applications.

Statement of significance

Hydrogen sulfide, as a gaseous messenger, plays a crucial role in many physiological and pathological conditions. Recent studies about functions of H₂S suggests H₂S-based therapy could be promising therapeutic strategy for many diseases, such as cardiovascular disease, arthritis, and inflammatory bowel disease. Although many H₂S donors have been developed and applied for biomedical studies, most of H₂S donors have the shortage that the H₂S release is either too fast or uncontrollable, which poorly mimic the biological generation of H₂S. By simply combining electrospinning technique with our designed biological thiols activated H₂S donor, NSHD1, we fabricated H₂S releasing microfibers (H₂S-fibers). This H₂S-fibers significantly prolonged the releasing time compared to H₂S donor alone. By adjusting the electrospinning parameters, tunable releasing profiles can be achieved. Moreover, the H₂S fibers can protect cardiac myoblasts H9c2 and fibroblast NIH 3T3 from oxidative damage and support their proliferation as cellular scaffolds. To our knowledge, this is the first report of electrospun fibers with H₂S releasing capacity. We anticipate this H₂S-releasing scaffold will have great potential for biomedical applications.

Labeling of Enveloped Virus via Metabolic Incorporation of Azido Sugars

Co-reporter:Xia Zhao, Li Cai, Enoch A. Adogla, Hong Guan, Yuan Lin, and Qian Wang

Bioconjugate Chemistry 2015 Volume 26(Issue 9) pp:1868

Publication Date(Web):August 26, 2015

DOI:10.1021/acs.bioconjchem.5b00310

Modification of an enveloped measles virus was achieved by metabolic incorporation of azido sugars in host cells through the protein glycosylation process. Based on this, the resulting measles virus particles could be modified with azido groups on the surface glycoproteins, which could be further labeled with fluorescence dyes using a strain-promoted azide–alkyne cycloaddition reaction. We envision this metabolic labeling approach to be applicable to a wide variety of enveloped viruses, allowing the facile conjugation and surface modification.

Plant virus incorporated hydrogels as scaffolds for tissue engineering possess low immunogenicity in vivo

Co-reporter:Jittima Amie Luckanagul;L. Andrew Lee;Shaojin You;Xiaoming Yang

Journal of Biomedical Materials Research Part A 2015 Volume 103( Issue 3) pp:887-895

Publication Date(Web):

DOI:10.1002/jbm.a.35227

Abstract

Viruses are no longer recognized purely for being ubiquitous pathogens, but have served as building blocks for material chemistry and nanotechnology. Thousands of coat protein subunits of a viral particle can be modified chemically and/or genetically. We have previously shown that the three-dimensional porous hydrogels can easily be functionalized by Tobacco mosaic virus (TMV), a rod-like plant virus, using its mutant, RGD-TMV. RGD-TMV hosted bioadhesive peptide (RGD) in the hydrogel, which was shown to enhance cell attachment and promote osteogenic differentiation of cultured stem cell. To translate this technology to potential clinical applications, we sought to study the biocompatibility of the hydrogel. In this paper, the hydrogels were implanted in vivo and assessed for their immunogenicity, toxicity, and biodegradability. Immune response for TMV substantially decreased when incorporated in the hydrogel implants. The implanted TMV hydrogels exhibited no apparent toxicity and were degradable in mice. The results highlighted the feasibility of using TMV incorporated hydrogels as scaffolding materials for regenerative medicine in terms of biocompatibility and biodegradability. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 887–895, 2015.

Genetically Engineered Plant Viral Nanoparticles Direct Neural Cells Differentiation and Orientation

Co-reporter:Sheng Feng, Lin Lu, Xingjie Zan, Yehong Wu, Yuan Lin, and Qian Wang

Langmuir 2015 Volume 31(Issue 34) pp:9402-9409

Publication Date(Web):August 6, 2015

DOI:10.1021/acs.langmuir.5b02226

An important aim of tissue engineering is to design biomimetic materials with specific cell binding motifs and precisely controlled structural organization, thereby providing biochemical and physical cues for desired cellular behaviors. Previously, our group generated genetically modified tobacco mosaic virus (TMV) displaying integrin binding motifs, RGD1, RGD7, PSHRN3, P15, and DGEA. The resulting rod-like virus particles displaying integrin binding motifs were biocompatible with Neuro 2A (N2a), a mouse neural crest-derived cell line, and could promote the neurite outgrowth of N2a. The genetically modified viruses could be assembled with aligned orientation in the capillary by applying a shear force. The resulting aligned substrates were able to dictate directional neurite outgrowth of N2a cells. Therefore, this method could be potentially applied for neural tissue engineering, as a neural conduit for repairing peripheral nerve injuries.

Charge-transfer interactions for the fabrication of multifunctional viral nanoparticles

Co-reporter:Jun Hu, Peiyi Wang, Xia Zhao, Lin Lv, Song Yang, Baoan Song and Qian Wang

Chemical Communications 2014 vol. 50(Issue 91) pp:14125-14128

Publication Date(Web):16 Sep 2014

DOI:10.1039/C4CC05195E

A facile strategy to fabricate multifunctional viral nanoparticles was described by introducing charge-transfer interactions between a pyrenyl motif with dinitrophenyl and pyridinium-contained guest molecules.

Dual responsive supramolecular amphiphiles: guest molecules dictate the architecture of pyridinium-tailored anthracene assemblies

Co-reporter:Jun Hu, Peiyi Wang, Yuan Lin, Song Yang, Baoan Song and Qian Wang

Organic & Biomolecular Chemistry 2014 vol. 12(Issue 27) pp:4820-4823

Publication Date(Web):27 May 2014

DOI:10.1039/C4OB00936C

By introducing an electron-deficient guest molecule and a counter anion, the assembly morphology of 1-[11-(2-anthracenylmethoxy)-11-oxoundecyl]pyridinium bromide (2-AP) was transformed to microsheets and nanofibers from microtubes, respectively.

Self-Assembly of Pyridinium-Functionalized Anthracenes: Molecular-Skeleton-Directed Formation of Microsheets and Microtubes

Co-reporter:Dr. Jun Hu;Peiyi Wang; Yuan Lin; Jidong Zhang;Dr. Mark Smith;Dr. Perry J. Pellechia; Song Yang; Baoan Song; Qian Wang

Chemistry - A European Journal 2014 Volume 20( Issue 25) pp:7603-7607

Publication Date(Web):

DOI:10.1002/chem.201402631

Abstract

Two amphiphilic regioisomers, 9-AP (1-[11-(9-anthracenylmethoxy)-11-oxoundecyl]pyridinium bromide), and 2-AP (1-[11-(2-anthracenyl methoxy)-11-oxoundecyl]pyridinium bromide), were synthesized and their assembly behaviors were studied. Due to the anisotropic features of the anthracene structure, different substituted positions on the anthracene ring lead 9-AP and 2-AP to adapt “shaver” and “spatula”-like molecular shapes, respectively, which consequently dictate the structure of their final assemblies. While “shaver”-shaped 9-AP assembled into microsheets, driven by π–π interactions, “spatula”-shaped 2-AP assembled into microtubular structures, promoted primarily by charge-transfer interactions.

Facile Co-Assembly Process to Generate Core–Shell Nanoparticles with Functional Protein Corona

Co-reporter:Nisaraporn Suthiwangcharoen, Tao Li, Laying Wu, Heidi B. Reno, Preston Thompson, and Qian Wang

Biomacromolecules 2014 Volume 15(Issue 3) pp:

Publication Date(Web):February 3, 2014

DOI:10.1021/bm401819x

A simple and robust protocol to maintain the structural feature of polymer–protein core–shell nanoparticles (PPCS-NPs) is developed based on the synergistic interactions between proteins and functional polymers. Using the self-assembly method, a broad range of proteins can be assembled to the selective water-insoluble polymers containing pyridine groups. The detailed analysis of the PPCS-NPs structure was conducted using FESEM and thin-sectioned TEM. The results illustrated that the protein molecules are located on the corona of the PPCS-NPs. While proteins are displacing between water and polymer to minimize the interfacial energy, the polymer offers a unique microenvironment to maintain protein structure and conformation. The proposed mechanism is based on a fine balance between hydrophobicity and hydrophilicity, as well as hydrogen bonding between proteins and polymer. The PPCS-NPs can serve as a scaffold to incorporate both glucose oxidase (GOX) and horseradish peroxidase (HRP) onto a single particle. Such a GOX-HRP bienzymatic system showed a ∼20% increase in activity in comparison to the mixed free enzymes. Our method therefore provides a unique platform to preserve protein structure and conformation and can be extended to a number of biomolecules.

Caged Peptides to Control Enzymatic Activity within Hydrogel Scaffolds

Co-reporter: Dr. Yuan Lin; Dr. Qian Wang

ChemBioChem 2014 Volume 15( Issue 6) pp:787-788

Publication Date(Web):

DOI:10.1002/cbic.201400071

A supramolecular strategy to assemble multifunctional viral nanoparticles

Co-reporter:Limin Chen, Xia Zhao, Yuan Lin, Yubin Huang and Qian Wang

Chemical Communications 2013 vol. 49(Issue 83) pp:9678-9680

Publication Date(Web):21 Aug 2013

DOI:10.1039/C3CC45559A

Using a one-pot approach driven by the supramolecular interaction between β-cyclodextrin and adamantyl moieties, multifunctional viral nanoparticles can be facilely formulated for biomedical applications.

In Vivo Virus-Based Macrofluorogenic Probes Target Azide-Labeled Surface Glycans in MCF-7 Breast Cancer Cells

Co-reporter:Clorissa L. Washington-Hughes, Yixing Cheng, Xinrui Duan, Li Cai, L. Andrew Lee, and Qian Wang

Molecular Pharmaceutics 2013 Volume 10(Issue 1) pp:43-50

Publication Date(Web):September 21, 2012

DOI:10.1021/mp3002528

Chemical addressability of viral particles has played a pivotal role in adapting these biogenic macromolecules for various applications ranging from medicine to inorganic catalysis. Cowpea mosaic virus possesses multiple features that are advantageous for the next generation of virus-based nanotechnology: consistent multimeric assemblies dictated by its genetic code, facile large scale production, and lack of observable toxicity in humans. Herein, the chemistry of the viral particles is extended with the use of Cu-free strain-promoted azide–alkyne cycloaddition reaction, or SPAAC reaction. The elimination of Cu, its cocatalyst and reducing agent, simplifies the reaction scheme to a more straightforward approach, which can be directly applied to living systems. As a proof of concept, the viral particles modified with the azadibenzylcyclooctyne functional groups are utilized to trigger and amplify a weak fluorescent signal (azidocoumarin) in live cell cultures to visualize the non-natural sugars. Future adaptations of this platform may be developed to enhance biosensing applications.Keywords: bioconjugation; bionanoparticles; click chemistry; Cowpea mosaic virus; fluorogenic dye; strain-promoted alkyne−azide cycloaddition (SPAAC) reaction;

An acid catalyzed reversible ring-opening/ring-closure reaction involving a cyano-rhodamine spirolactam

Co-reporter:Honglin Li, Hong Guan, Xinrui Duan, Jun Hu, Guiren Wang and Qian Wang

Organic & Biomolecular Chemistry 2013 vol. 11(Issue 11) pp:1805-1809

Publication Date(Web):22 Jan 2013

DOI:10.1039/C3OB27356C

Cyanamide was introduced into the rhodamine spirolactam framework to produce a colorless and non-fluorescent compound RBCN. It shows a reversible ring-opening/ring-closure process in response to the solution pH, which exhibits an “ON/OFF” switching in its fluorescence. Different from other rhodamine-type dyes, the ring-open form of RBCN is stable in protic solvents under neutral, near neutral and basic conditions, showing a pink color and very strong fluorescence. We also demonstrated the potential of RBCN in live cell imaging.

Expansion of breast cancer stem cells with fibrous scaffolds

Co-reporter:Sheng Feng, Xinrui Duan, Pang-Kuo Lo, Shou Liu, Xinfeng Liu, Hexin Chen and Qian Wang

Integrative Biology 2013 vol. 5(Issue 5) pp:768-777

Publication Date(Web):01 Mar 2013

DOI:10.1039/C3IB20255K

Cancer stem cells (CSCs) are hypothesized as tumor-initiating cells within tumors and main contributors of tumor growth, metastasis and recurrence. Mammary cancer cells, MCF-7 cells, were cultured on 3D polycaprolactone (PCL) fibrous scaffolds, showing an increased proportion of CSCs. The expression of stem cell markers, including OCT3/4 and SOX2, and breast CSC-specific markers, SOX4 and CD49f, was significantly upregulated, and the mammosphere-forming capability in cells cultured on PCL fibrous scaffolds increased. The fibrous scaffolds also induced the elongation of MCF-7 cells and extended cell proliferation. The increase of CSC properties after being cultured on fibrous scaffolds was further confirmed with two luminal-type mammary cell lines, T47D and SK-BR-3, and a basal-type cell line, MDA-MB-231, by ALDEFLUOR assay and mammosphere formation assay. Moreover, we observed the upregulation of epithelial to mesenchymal transition and increased invasive capability in cells cultured on PCL fibrous scaffolds. These data suggest that the increase of CSC proportion in a 3D culture system may account for the enhanced malignancy. Therefore, our PCL fibrous scaffolds can potentially be used for CSCs enrichment and anti-cancer drug screening.

Biomolecular Assembly of Thermoresponsive Superlattices of the Tobacco Mosaic Virus with Large Tunable Interparticle Distances

Co-reporter:Dr. Tao Li;Dr. Xingjie Zan;Dr. Rall E. Winans; Qian Wang;Dr. Byeongdu Lee

Angewandte Chemie 2013 Volume 125( Issue 26) pp:6770-6774

Publication Date(Web):

DOI:10.1002/ange.201209299

Facile Method for Large Scale Alignment of One Dimensional Nanoparticles and Control over Myoblast Orientation and Differentiation

Co-reporter:Xingjie Zan, Sheng Feng, Elizabeth Balizan, Yuan Lin, and Qian Wang

ACS Nano 2013 Volume 7(Issue 10) pp:8385

Publication Date(Web):September 4, 2013

DOI:10.1021/nn403908k

A facile and robust method to align one-dimensional (1D) nanoparticles (NPs) in large scale has been developed. Using flow assembly, representative rod-like nanoparticles, including tobacco mosaic virus (TMV), gold nanorods, and bacteriophage M13, have been aligned inside glass tubes by controlling flow rate and substrate surface properties. The properties of 1D NPs, such as stiffness and aspect ratio, play a critical role in the alignment. Furthermore, these hierarchically organized structures can be used to support cell growth and control the cell orientation and morphology. When C2C12 myoblasts were cultured on surfaces coated with aligned TMV, we found that nanoscale topographic features were critical to guide the cell orientation and myogenic differentiation. This method can therefore be used in the fabrication of complex assemblies with 1D NPs and have wide applications in tissue engineering, sensing, electronics, and optical fields.Keywords: 1D nanoparticles; alignment; capillary; myogenic differentiation; self-assembly; tobacco mosaic virus

Incorporation of azide sugar analogue decreases tumorigenic potential of breast cancer cells by reducing cancer stem cell population

Co-reporter:XinRui Duan;Li Cai;Lim Andrew Lee;HeXin Chen

Science China Chemistry 2013 Volume 56( Issue 3) pp:279-285

Publication Date(Web):2013 March

DOI:10.1007/s11426-012-4806-4

The azido sugar, GalNAz, was successfully used for imaging and perturbing protein glycosylation in triple-negative breast cancer cell line, MDA-MB-231. After the incorporation of GalNAz in the triple-negative breast cancer cell line, the tumorigenicity of these cells was decreased. Results from gene analysis and drug treatment suggest that the tumorigenicity decrease may be attributed to the reduction of cancer stem cell population. Possible mechanisms of GalNAz induced cancer stem cells (CSCs) proportion change are discussed.

Biomolecular Assembly of Thermoresponsive Superlattices of the Tobacco Mosaic Virus with Large Tunable Interparticle Distances

Co-reporter:Dr. Tao Li;Dr. Xingjie Zan;Dr. Rall E. Winans; Qian Wang;Dr. Byeongdu Lee

Angewandte Chemie International Edition 2013 Volume 52( Issue 26) pp:6638-6642

Publication Date(Web):

DOI:10.1002/anie.201209299

Self-Assembly of Rodlike Virus to Superlattices

Co-reporter:Tao Li, Xingjie Zan, Yong Sun, Xiaobing Zuo, Xiaodong Li, Andrew Senesi, Randall E. Winans, Qian Wang, and Byeongdu Lee

Langmuir 2013 Volume 29(Issue 41) pp:12777-12784

Publication Date(Web):September 18, 2013

DOI:10.1021/la402933q

Rodlike tobacco mosaic virus (TMV) has been found to assemble into superlattices in aqueous solution using the polymer methylcellulose to induce depletion and free volume entropy-based attractive forces. Both transmission electron microscopy and small-angle X-ray scattering show that the superlattices form in both semidilute and concentrated regimes of polymer, where the free volume entropy and the depletion interaction are the dominant driving force, respectively. The superlattices are NaCl and temperature responsive. The rigidity of the rodlike nanoparticles also plays an important role for the formation of superlattices through the free volume entropy mechanism. Compared to the rigid TMV particle, flexible bacteriophage M13 particles are only responsive to the depletion force and thus only assemble in highly concentrated polymer solution, where depletion interaction is dominant.

Discrimination of colon cancer stem cells using noncanonical amino acid

Co-reporter:Xinrui Duan, Honglin Li, Hexin Chen and Qian Wang

Chemical Communications 2012 vol. 48(Issue 72) pp:9035-9037

Publication Date(Web):20 Jul 2012

DOI:10.1039/C2CC33776B

Cancer stem cells (CSCs) may be responsible for tumor recurrence. Metabolic labelling of newly synthesized proteins with non-canonical amino acids allows us to discriminate CSCs in mixed populations due to the quiescent nature of these cells.

Tobacco Mosaic Virus as a New Carrier for Tumor Associated Carbohydrate Antigens

Co-reporter:Zhaojun Yin, Huong Giang Nguyen, Sudipa Chowdhury, Philip Bentley, Michael A. Bruckman, Adeline Miermont, Jeffrey C. Gildersleeve, Qian Wang, and Xuefei Huang

Bioconjugate Chemistry 2012 Volume 23(Issue 8) pp:1694

Publication Date(Web):July 19, 2012

DOI:10.1021/bc300244a

Tumor-associated carbohydrate antigens (TACAs) are being actively studied as targets for antitumor vaccine development. One serious challenge was the low immunogenecity of these antigens. Herein, we report the results of using the tobacco mosaic virus (TMV) capsid as a promising carrier of a weakly immunogenic TACA, the monomeric Tn antigen. The copper(I) catalyzed azide–alkyne cycloaddition reaction was highly efficient in covalently linking Tn onto the TMV capsid without resorting to a large excess of the Tn antigen. The location of Tn attachment turned out to be important. Tn introduced at the N terminus of TMV was immunosilent, while that attached to tyrosine 139 elicited strong immune responses. Both Tn specific IgG and IgM antibodies were generated as determined by enzyme-linked immunosorbent assay and a glycan microarray screening study. The production of high titers of IgG antibodies suggested that the TMV platform contained the requisite epitopes for helper T cells and was able to induce antibody isotype switching. The antibodies exhibited strong reactivities toward Tn antigen displayed in its native environment, i.e., cancer cell surface, thus highlighting the potential of TMV as a promising TACA carrier.

Thermally Controlled Release of Anticancer Drug from Self-Assembled γ-Substituted Amphiphilic Poly(ε-caprolactone) Micellar Nanoparticles

Co-reporter:Yixing Cheng, Jing Hao, L. Andrew Lee, Michael C. Biewer, Qian Wang, and Mihaela C. Stefan

Biomacromolecules 2012 Volume 13(Issue 7) pp:

Publication Date(Web):June 9, 2012

DOI:10.1021/bm300823y

A thermo-responsive poly{γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ε-caprolactone}-b-poly(γ-octyloxy-ε-caprolactone) (PMEEECL-b-POCTCL) diblock copolymer was synthesized by ring-opening polymerization using tin octanoate (Sn(Oct)2) catalyst and a fluorescent dansyl initiator. The PMEEECL-b-POCTCL had a lower critical solution temperature (LCST) of 38 °C, and it was employed to prepare thermally responsive micelles. Nile Red and Doxorubicin (DOX) were loaded into the micelles, and the micellar stability and drug carrying ability were investigated. The size and the morphology of the cargo-loaded micelles were determined by DLS, AFM, and TEM. The Nile-Red-loaded polymeric micelles were found to be stable in the presence of both fetal bovine serum and bovine serum albumin over a 72 h period and displayed thermo-responsive in vitro drug release. The blank micelles showed a low cytotoxicity. As comparison, the micelles loaded with DOX showed a much higher in vitro cytotoxicity against MCF-7 human breast cancer cell line when the incubation temperature was elevated above the LCST. Confocal laser scanning microscopy was used to study the cellular uptake and showed that the DOX-loaded micelles were internalized into the cells via an endocytosis pathway.

Biological thiols-triggered hydrogen sulfide releasing microfibers for tissue engineering applications

Co-reporter:Sheng Feng, Yu Zhao, Ming Xian, Qian Wang

Acta Biomaterialia (November 2015) Volume 27() pp:205-213

Publication Date(Web):1 November 2015

DOI:10.1016/j.actbio.2015.09.010

By electrospinning of polycaprolactone (PCL) solutions containing N-(benzoylthio)benzamide (NSHD1), a H2S donor, fibrous scaffolds with hydrogen sulfide (H2S) releasing capability (H2S-fibers) are fabricated. The resultant microfibers are capable of releasing H2S upon immersion in aqueous solution containing biological thiols under physiological conditions. The H2S release peaks of H2S-fibers appeared at 2–4 h, while the peak of donor alone showed at 45 min. H2S release half-lives of H2S-fibers were 10–20 times longer than that of donor alone. Furthermore, H2S-fibers can protect cells from H2O2 induced oxidative damage by significantly decreasing the production of intracellular reactive oxygen species (ROS). Finally, we investigated the H2S-fibers application as a wound dressing in vitro. Given that H2S has a broad range of physiological functions, H2S-fibers hold great potential for various biomedical applications.Statement of significanceHydrogen sulfide, as a gaseous messenger, plays a crucial role in many physiological and pathological conditions. Recent studies about functions of H2S suggests H2S-based therapy could be promising therapeutic strategy for many diseases, such as cardiovascular disease, arthritis, and inflammatory bowel disease. Although many H2S donors have been developed and applied for biomedical studies, most of H2S donors have the shortage that the H2S release is either too fast or uncontrollable, which poorly mimic the biological generation of H2S. By simply combining electrospinning technique with our designed biological thiols activated H2S donor, NSHD1, we fabricated H2S releasing microfibers (H2S-fibers). This H2S-fibers significantly prolonged the releasing time compared to H2S donor alone. By adjusting the electrospinning parameters, tunable releasing profiles can be achieved. Moreover, the H2S fibers can protect cardiac myoblasts H9c2 and fibroblast NIH 3T3 from oxidative damage and support their proliferation as cellular scaffolds. To our knowledge, this is the first report of electrospun fibers with H2S releasing capacity. We anticipate this H2S-releasing scaffold will have great potential for biomedical applications.Download high-res image (149KB)Download full-size image

Discrimination of colon cancer stem cells using noncanonical amino acid

Co-reporter:Xinrui Duan, Honglin Li, Hexin Chen and Qian Wang

Chemical Communications 2012 - vol. 48(Issue 72) pp:NaN9037-9037

Publication Date(Web):2012/07/20

DOI:10.1039/C2CC33776B

Virus-templated FRET platform for the rational design of ratiometric fluorescent nanosensors

Co-reporter:Limin Chen, Yehong Wu, Yuan Lin and Qian Wang

Chemical Communications 2015 - vol. 51(Issue 50) pp:NaN10193-10193

Publication Date(Web):2015/05/14

DOI:10.1039/C5CC02866C

A supramolecular strategy to assemble multifunctional viral nanoparticles

Co-reporter:Limin Chen, Xia Zhao, Yuan Lin, Yubin Huang and Qian Wang