Zheng-Wei Mao

Find an error

Name:

Organization: Zhejiang University , China

Department: Department of Polymer Science and Engineering

Title: (PhD)

TOPICS

Material Chemistry

Graphene & Graphite

Polymer

Atom Transfer Radical Polymerization Polyelectrolyte

Chemicals
References

Antitumor Activity of a Unique Polymer That Incorporates a Fluorescent Self-Assembled Metallacycle

Co-reporter:Guocan Yu, Mingming Zhang, Manik Lal Saha, Zhengwei Mao, Jin Chen, Yong Yao, Zijian Zhou, Yijing Liu, Changyou Gao, Feihe Huang, Xiaoyuan Chen, and Peter J. Stang

Journal of the American Chemical Society November 8, 2017 Volume 139(Issue 44) pp:15940-15940

Publication Date(Web):October 11, 2017

DOI:10.1021/jacs.7b09224

Despite the well-known anticancer activity of mono- and multinuclear platinum complexes, studies of the antitumor performances of platinum-based supramolecular coordination complexes are rare. Herein, we report on the synthesis of a four-armed amphiphilic copolymer, Pt-PAZMB-b-POEGMA, containing a metallacycle M, in which the tetraphenylethene derivative acts as an aggregation-induced emissive fluorescent probe for live cell imaging and the 3,6-bis[trans-Pt(PEt3)2]phenanthrene (PhenPt) is an anticancer drug. This copolymer was further self-assembled into nanoparticles of different sizes and vesicles depending upon the experimental conditions. The impacts of the morphology and size of the assemblies on their endocytic pathways, uptake rates, internalization amounts, and cytotoxicities were investigated. The self-assemblies were further employed to encapsulate doxorubicin (DOX) to achieve a synergistic anticancer effect. Controlled drug release was also realized via amphiphilicity changes and was driven by a glutathione-induced cascade elimination reaction. The DOX-loaded nanoparticles of around 50 nm in size exhibited an excellent antitumor performance as well as a low systemic toxicity, due to an enhanced permeability and retention effect.

Application of melatonin-loaded poly(N-isopropylacrylamide) hydrogel particles to reduce the toxicity of airborne pollutes to RAW264.7 cells

Co-reporter:Wenjing Zhang, Pengfei Jiang, Jin Chen, Chaonan Zhu, Zhengwei Mao, Changyou Gao

Journal of Colloid and Interface Science 2017 Volume 490(Volume 490) pp:

Publication Date(Web):15 March 2017

DOI:10.1016/j.jcis.2016.11.075

The adverse effect of airborne PM2.5 pollutes on human beings and the environment, most likely due to heavy metal leaching, has received extensive attention recently. It is urgently required to develop a simple and effective method to suppress the toxicity of PM2.5 pollutes. In this study, the heavy metal content of PM2.5 pollutes around Zhejiang university were firstly identified. Their cytotoxicity was confirmed, by inducing significantly enhanced intracellular reactive oxygen species level. Poly(N-isopropylacrylamide) (PNIPAM) submicron hydrogel particles with tunable crosslinking densities and thermo-responsive swelling/shrinking properties were then prepared by adjusting the crosslinking density. Anti-oxidant drug melatonin (MLT) was encapsulated into the obtained PNIPAM nanogel particles with the drug loading efficiency larger than 50%, achieving thermo-responsive drug release profile. The PNIPAM/MLT particles had a strong ability to reduce the cytotoxicity to Raw264.7 cells induced by the extractant of PM2.5 pollutes, as well as to suppress the intracellular reactive oxygen species (ROS) level and secretion of tumor necrosis factor alpha (TNF-α), especially when the cells were treated under 25 °C for 3 h after ingestion of the PNIPAM/MLT particles. This concept-proving study demonstrates the potential to use the thermo-responsive PNIPAM/MLT particles to suppress the toxicity of airborne PM2.5 pollutes, which is a paramount requirement for human health.Thermo-responsive PNIPAM microgel particles were used to encapsulate anti-oxidant drug melatonin to reduce the cytotoxicity of Raw264.7 cells induced by the extractant of PM2.5 pollutes by suppressing the intracellular ROS level.Download high-res image (137KB)Download full-size image

Polysarcosine brush stabilized gold nanorods for in vivo near-infrared photothermal tumor therapy

Co-reporter:Hong Zhu, Ying Chen, Fang-Jie Yan, Jin Chen, ... Zheng-Wei Mao

Acta Biomaterialia 2017 Volume 50(Volume 50) pp:

Publication Date(Web):1 March 2017

DOI:10.1016/j.actbio.2016.12.050

Gold nanorods (AuNRs) are suitable candidates for photothermal therapy in vivo, because of their excellent ability to transfer near-infrared (NIR) light into heat. However, appropriate surface should be generated on AuNRs before their in vivo application because of the low colloidal stability in complicate biological environment and relatively strong toxicity compared to their pristine stabilizer cetyltrimethylammonium bromide. In the current study, polysarcosine (PS), a non-ionic hydrophilic polypeptoid whose structure is similar to polypeptides, bearing repeating units of natural α-amino acid, was used to stabilize AuNRs due to its excellent hydrophilicity and biocompatibility.Polysarcosine with optimized molecular weight was synthesized and used to modify AuNRs by traditional ligand exchange. The grafting of PS on AuNRs was evidenced by fourier transform infrared (FTIR) spectroscopy and the alternation of surface zeta potential. The polysarcosine coated AuNRs (Au@PS) showed good stabilities in wide pH range and simulated physiological buffer with the ligand competition of dithiothreitol (DTT). The Au@PS NRs had neglectable cytotoxicity and showed efficient ablation of tumor cells in vitro. Moreover, Au@PS NRs had a longer circulation time in body that resulted in a higher accumulation in solid tumors after intravenous injection, compared to AuNRs capped with polyethylene glycol (PEG). Photothermal therapy in vivo demonstrated that the tumors were completely destroyed by single-time irradiation of NIR laser after one-time injection of the polysarcosine capped AuNRs. The Au@PS NRs did not cause obvious toxicity in vivo, suggesting promising potential in cancer therapy.Statement of SignificanceIn current study, polysarcosine (PS), a non-ionic hydrophilic polypeptoid whose structure is similar to polypeptides, bearing repeating units of natural α-amino acid, was used to stabilize AuNRs due to its excellent hydrophilicity and biocompatibility. The polysarcosine coated AuNRs (Au@PS) showed good stabilities in wide pH range and simulated physiological buffer. The Au@PS NRs had very low cytotoxicity and showed high efficacy for the ablation of cancer cells in vitro. Moreover, Au@PS NRs had a longer circulation time in blood that led to a higher accumulation in tumors after intravenous injection, compared to AuNRs capped with polyethylene glycol (PEG). In vivo photothermal therapy showed that tumors were completely cured without reoccurrence by one-time irradiation of NIR laser after a single injection of the polysarcosine modified AuNRs.Polysarcosine, a non-ionic hydrophilic polypeptoid can stabilize gold nanorods due to its excellent hydrophilicity and biocompatibility, enabling in vivo photothermal therapy to cure xenograft cancer.Download high-res image (152KB)Download full-size image

Pillar[5]arene-based chiral 3D polymer network for heterogeneous asymmetric catalysis

Co-reporter:Huangtianzhi Zhu;Bingbing Shi;Lina Gao;Yuezhou Liu;Pei-Ren Liu;Liqing Shangguan;Zhengwei Mao;Feihe Huang

Polymer Chemistry (2010-Present) 2017 vol. 8(Issue 46) pp:7108-7112

Publication Date(Web):2017/11/28

DOI:10.1039/C7PY01669G

A novel chiral 3D polymer network with evenly dispersed catalytic sites, good heterogeneous asymmetric catalytic ability and recyclability was easily constructed by pillar[5]arene and (R,R)-tetraaryl-1,3-dioxolane-4,5-dimethanol derivatives.

Suppressing the cytotoxicity of CuO nanoparticles by uptake of curcumin/BSA particles

Co-reporter:Wenjing Zhang, Pengfei Jiang, Ying Chen, Peihua Luo, Guanqun Li, Botuo Zheng, Wei Chen, Zhengwei Mao and Changyou Gao

Nanoscale 2016 vol. 8(Issue 18) pp:9572-9582

Publication Date(Web):21 Apr 2016

DOI:10.1039/C6NR02181F

The adverse effects of metal-based nanoparticles on human beings and the environment have received extensive attention recently. It is urgently required to develop a simple and effective method to suppress the toxicity of metal-based nanomaterials. In this study, a hydrophobic antioxidant and a chelation agent curcumin (CUR) were encapsulated into bovine serum albumin (BSA) particles by a simple co-precipitation method, and followed by glutaraldehyde cross-linking. The CUR/BSA particles had an average size of 300 nm in diameter with a negatively charged surface and sustained curcumin release properties. The cellular uptake and cytotoxicity of CUR/BSA particles were followed on A549 cells, HepG2 cells and RAW264.7 cells. The CUR/BSA particles had higher intracellular accumulation and lower cytotoxicity compared with the free curcumin at the same drug concentration. The CUR/BSA particles could suppress the cytotoxicity generated by CuO nanoparticles as a result of decrease of both the intracellular reactive oxygen species (ROS) level and Cu2+ concentration, while the free curcumin did not show any obvious detoxicating effect. The detoxicating effects of CUR/BSA particles were further studied in an intratracheal instillation model in vivo, demonstrating significant reduction of toxicity and inflammatory response in rat lungs induced by CuO nanoparticles. The concept-proving study demonstrates the potential of the CUR/BSA particles in suppressing cytotoxicity of metal-based nanomaterials, which is a paramount requirement for the safe application of nanotechnology.

Citrate-capped iron oxide nanoparticles impair the osteogenic differentiation potential of rat mesenchymal stem cells

Co-reporter:Surakshya Shrestha, Pengfei Jiang, Marcelo Henrique Sousa, Paulo Cesar Morais, Zhengwei Mao and Changyou Gao

Journal of Materials Chemistry A 2016 vol. 4(Issue 2) pp:245-256

Publication Date(Web):24 Nov 2015

DOI:10.1039/C5TB02007G

Surface modification of iron oxide nanoparticles may cause unexpected impact upon interaction with cells, such as cytotoxicity and change in the differentiation potential of stem cells. In this study, two kinds of iron oxide nanoparticles with different surface chemistries, i.e. one in its pristine form (P-NPs) without extra capping molecules and the other coated with citrate (C-NPs), and with similar sizes, ∼10 nm, as measured by transmission electron microscopy and X-ray diffractometry, were prepared. Both P-NPs and C-NPs aggregated to some extent in water, with hydrodynamic diameters of 211.4 ± 29 and 128.6 ± 6.3 nm, and surface zeta potential values of +23.5 ± 0.3 and −49.6 ± 0.5 mV, respectively. However, both NPs further aggregated to a similar extent with hydrodynamic diameters of 260 ± 5.5 and 214 ± 6.4 nm and with a slightly negative surface charge (∼−10 mV) in cell differentiation media. After being incubated with rat mesenchymal stem cells (MSCs) for 14 d, both types of NPs showed similar cell uptake kinetics and final intracellular iron content, i.e. 53.3 pg per cell for P-NPs and 59.9 pg per cell for C-NPs, and minimal cytotoxicity at a concentration below 100 μg mL−1. The adipogenic differentiation potential of MSCs was unaltered regardless of the NP types, and the P-NPs did not have an obvious impact on the osteogenic differentiation potential of MSCs. The osteogenic differentiation potential of the MSCs, however, was significantly impaired by incubation with the C-NPs, as evidenced by significantly reduced expression of osteogenic markers, namely collagen type I (COL) and osteocalcin (OCN) and calcium deposition. The uptake of C-NPs and surface-anchored citrate molecules were found to have a synergistic effect.

Preparation of an Arg-Glu-Asp-Val Peptide Density Gradient on Hyaluronic Acid-Coated Poly(ε-caprolactone) Film and Its Influence on the Selective Adhesion and Directional Migration of Endothelial Cells

Co-reporter:Shan Yu, Ying Gao, Xu Mei, Tanchen Ren, Su Liang, Zhengwei Mao, and Changyou Gao

ACS Applied Materials & Interfaces 2016 Volume 8(Issue 43) pp:29280

Publication Date(Web):October 10, 2016

DOI:10.1021/acsami.6b09375

Selective adhesion and migration of endothelial cells (ECs) over smooth muscle cells (SMCs) is very important in the rapid endothelialization of blood-contacting implants to prevent vascular restenosis. In this study, a uniform cell-resistant layer of methacrylate-functionalized hyaluronic acid (HA) was first immobilized on a poly(ε-caprolactone) (PCL) film via polydopamine coupling. Then, a density gradient of thiol-functionalized Arg-Glu-Asp-Val (REDV) peptide was prepared on the HA layer via thiol-ene click chemistry and the continuous injection method. The REDV gradient selectively enhanced EC adhesion and preferential directional migration toward the region of higher REDV density, reaching 86% directionality in the middle of the gradient. The migration rate of ECs was also significantly enhanced twofold compared with that on tissue culture polystyrene (TCPS). In contrast, the gradient significantly weakened the adhesion of SMCs to 25% of that on TCPS but had no obvious impact on the migration rate and directionality. Successful modulation of the selective adhesion and directional migration of ECs over SMCs on biodegradable polymers serves as an important step toward practical applications for guided tissue regeneration.Keywords: endothelial cells; gradient materials; PCL film; REDV peptide; selective cell migration; smooth muscle cells

Fe3O4/BSA particles induce osteogenic differentiation of mesenchymal stem cells under static magnetic field

Co-reporter:Pengfei Jiang, Yixian Zhang, Chaonan Zhu, Wenjing Zhang, Zhengwei Mao, Changyou Gao

Acta Biomaterialia 2016 Volume 46() pp:141-150

Publication Date(Web):December 2016

DOI:10.1016/j.actbio.2016.09.020

Abstract

Differentiation of stem cells is influenced by many factors, yet uptake of the magnetic particles with or without magnetic field is rarely tackled. In this study, iron oxide nanoparticles-loaded bovine serum albumin (BSA) (Fe₃O₄/BSA) particles were prepared, which showed a spherical morphology with a diameter below 200 nm, negatively charged surface, and tunable magnetic property. The particles could be internalized into bone marrow mesenchymal stem cells (MSCs), and their release from the cells was significantly retarded under external magnetic field, resulting in almost twice intracellular amount of the particles within 21 d compared to that of the magnetic field free control. Uptake of the Fe₃O₄/BSA particles enhanced significantly the osteogenic differentiation of MSCs under a static magnetic field, as evidenced by elevated alkaline phosphatase (ALP) activity, calcium deposition, and expressions of collagen type I and osteocalcin at both mRNA and protein levels. Therefore, uptake of the Fe₃O₄/BSA particles brings significant influence on the differentiation of MSCs under magnetic field, and thereby should be paid great attention for practical applications.

Statement of Significance

Differentiation of stem cells is influenced by many factors, yet uptake of the magnetic particles with or without magnetic field is rarely tackled. In this study, iron oxide nanoparticles-loaded bovine serum albumin (BSA) (Fe₃O₄/BSA) particles with a diameter below 200 nm, negatively charged surface, tunable Fe₃O₄ content and subsequently adjustable magnetic property were prepared. The particles could be internalized into bone marrow mesenchymal stem cells (MSCs), and their release from the cells was significantly retarded under external magnetic field. Uptake of the Fe₃O₄/BSA particles enhanced significantly the osteogenic differentiation of MSCs under a constant static magnetic field, while the magnetic particles and external magnetic field alone do not influence significantly the osteogenic differentiation potential of MSCs regardless of the uptake amount. The results demonstrate a potential magnetic manipulation method for stem cell differentiation, and also convey the significance of careful evaluation of the safety issue of magnetic particles in real an application situation.

Encapsulation of indocyanine green into cell membrane capsules for photothermal cancer therapy

Co-reporter:Guoping Sheng, Ying Chen, Lijie Han, Yong Huang, Xiaoli Liu, Lanjuan Li, Zhengwei Mao

Acta Biomaterialia 2016 Volume 43() pp:251-261

Publication Date(Web):1 October 2016

DOI:10.1016/j.actbio.2016.07.012

Abstract

Although indocyanine green (ICG) has promising applications in photothermal therapy (PPT) because of its low toxicity and high efficiency in inducing heat and singlet oxygen formation in response to near-infrared light with a wavelength of approximately 800 nm, its clinical application has been restricted because of its rapid body clearance and poor water stability. Therefore, cell membrane capsules (CMCs) derived from mammalian cells were used to encapsulate negatively charged ICG by temporarily permeating the plasma membrane and resealing using positively charged doxorubicin hydrochloride (DOX). The resulting CMCs@DOX/ICG exhibited a spherical shape, with a diameter of approximately 800 nm. The DOX and ICG encapsulation was confirmed by the UV–vis spectrum; a very small amount of DOX (0.8 μg) and a very high amount of ICG (∼110 μg) were encapsulated in 200 μg CMCs. Encapsulation in the CMCs leads to sustained release of ICG, especially in the presence of positively charged DOX. The temperature enhancement and generation of ROS by ICG encapsulated in CMCs were confirmed upon laser irradiation in vitro, leading to cell death. CMCs@DOX/ICG also can significantly enhance the retention of ICG in a tumor after intratumoral injection in vivo. As a result, combination treatment with CMCs@DOX/ICG and laser irradiation demonstrated much better anticancer efficacy than that of free DOX/ICG and CMCs@ICG. The encapsulation of ICG into CMCs, especially with the assistance of DOX, significantly slows down the body clearance of ICG, with a retained PPT effect against tumors, an important step forward in the practical application of ICG in cancer therapy.

Statement of Significance

In this study, cell membrane capsules (CMCs) derived from mammalian cells were used to encapsulate negatively charged indocyanine green (ICG) by temporarily permeating the plasma membrane and resealing, in the presence of positively charged doxorubicin hydrochloride (DOX). The resulting CMCs@DOX/ICG exhibited a spherical shape, with a diameter of approximately 800 nm. Encapsulation in the CMCs leads to sustained release of ICG and thus slower clearance inside body, especially in the presence of positively charged DOX. The system provides a better photothermal effect against tumors, an important step forward in the practical application of ICG in cancer therapy.

Cellular uptake of poly(allylamine hydrochloride) microcapsules with different deformability and its influence on cell functions

Co-reporter:Wei Yu, Wenbo Zhang, Ying Chen, Xiaoxue Song, Weijun Tong, Zhengwei Mao, Changyou Gao

Journal of Colloid and Interface Science 2016 Volume 465() pp:149-157

Publication Date(Web):1 March 2016

DOI:10.1016/j.jcis.2015.11.065

It is important to understand the safety issue and cell interaction pattern of polyelectrolyte microcapsules with different deformability before their use in biomedical applications. In this study, SiO2, poly(sodium-p-styrenesulfonate) (PSS) doped CaCO3 and porous CaCO3 spheres, all about 4 μm in diameter, were used as templates to prepare microcapsules with different inner structure and subsequent deformability. As a result, three kinds of covalently assembled poly(allylaminehydrochloride)/glutaraldehyde (PAH/GA) microcapsules with similar size but different deformability under external osmotic pressure were prepared. The impact of different microcapsules on cell viability and functions are studied using smooth muscle cells (SMCs), endothelial cells (ECs) and HepG2 cells. The results demonstrated that viabilities of SMCs, ECs and HepG2 cells were not significantly influenced by either of the three kinds of microcapsules. However, the adhesion ability of SMCs and ECs as well as the mobility of SMCs, ECs and HepG2 cells were significantly impaired after treatment with microcapsules in a deformability dependent manner, especially the microcapsules with lower deformability caused higher impairment on cell functions. The cellular uptake kinetics, uptake pathways, intracellular distribution of microcapsules are further investigated in SMCs to reveal the potential mechanism. The SMCs showed faster uptake rate and exocytosis rate of microcapsules with lower deformability (Cap@CaCO3/PSS and Cap@CaCO3), leading to higher intracellular accumulation of microcapsules with lower deformability and possibly larger retardation of cell functions. The results pointed out that the deformability of microcapsules is an important factor governing the biological performance of microcapsules, which requires careful adjustment for further biomedical applications.Cells showed faster uptake rate of microcapsules with lower deformability, leading to higher intracellular accumulation and subsequent higher impairment on cell functions.

Gold nanoparticles coated with polysarcosine brushes to enhance their colloidal stability and circulation time in vivo

Co-reporter:Ying Chen, Zhengqing Xu, Difeng Zhu, Xinfeng Tao, Yuqian Gao, Hong Zhu, Zhengwei Mao, Jun Ling

Journal of Colloid and Interface Science 2016 Volume 483() pp:201-210

Publication Date(Web):1 December 2016

DOI:10.1016/j.jcis.2016.08.038

Polysarcosine (PS), a non-ionic hydrophilic polypeptoid whose structure is similar to polypeptides, bearing repeating units of natural α-amino acid, has been used to stabilize gold nanoparticles (AuNPs) due to its excellent hydrophilicity and biocompatibility. Disulfide functionalized polysarcosines with different molecular weight were synthesized and used to cap AuNPs by traditional ligand exchange. The grafting of PS on AuNPs was evidenced by Fourier transform infrared (FTIR) spectroscopy and the alternation of surface zeta potential. The polysarcosine coated AuNPs (Au@PS) showed good stabilities in wide pH range and saline condition. They had strong resistance to ligand competition of dithiothreitol (DTT). They showed good stability in serum, with a molecular weight dependent interaction pattern with proteins. The Au@PS had very low cytotoxicity and cell uptake in vitro. Based on the results in vitro, polysarcosine with molecular weight of 5 kD with the best ability to stabilize AuNPs was used for in vivo test. The Au@PS had a longer circulation time in blood after intravenous injection than that of Au@PEG, indicating a better stealth-like property of polysarcosine. The Au@PS did not cause obvious toxicity in vivo, suggesting potential applications in disease diagnosis and therapy.Polysarcosine stabilized gold nanoparticles have high colloidal stability, low cell recognition and uptake in vitro, long circulation time and low toxicity in vivo, suggesting potential applications of polysarcosine as a nature inspired coating of nanomaterials in biomedical field.

Integration of antimicrobial peptides with gold nanoparticles as unique non-viral vectors for gene delivery to mesenchymal stem cells with antibacterial activity

Co-reporter:Li-Hua Peng, Yan-Fen Huang, Chen-Zhen Zhang, Jie Niu, Ying Chen, Yang Chu, Zhi-Hong Jiang, Jian-Qing Gao, Zheng-Wei Mao

Biomaterials 2016 103() pp: 137-149

Publication Date(Web):October 2016

DOI:10.1016/j.biomaterials.2016.06.057

Gold nanoparticles (AuNPs) have emerged as attractive non-viral gene vectors. However their application in regenerative medicine is still limited partially due to a lack of an intrinsic capacity to transfect difficult-to-transfect cells such as primary cells or stem cells. In current study, we report the synthesis of antimicrobial peptide conjugated cationic AuNPs (AuNPs@PEP) as highly efficient carriers for gene delivery to stem cells with antibacterial ability. The AuNPs@PEP integrate the advantages of cationic AuNPs and antibacterial peptides: the presence of cationic AuNPs can effectively condense DNA and the antimicrobial peptides are essential for the cellular & nucleus entry enhancement to achieve high transfection efficiency and antibacterial ability. As a result, antimicrobial peptides conjugated AuNPs significantly promoted the gene transfection efficiency in rat mesenchymal stem cells than pristine AuNPs, with a similar extent to those expressed by TAT (a well-known cell-penetrating peptide) modified AuNPs. More interestingly, the combinational system has better antibacterial ability than free antimicrobial peptides in vitro and in vivo, possibly due to the high density of peptides on the surface of AuNPs. Finally we present the concept-proving results that AuPs@PEP can be used as a carrier for in vivo gene activation in tissue regeneration, suggesting its potential as a multifunctional system with both gene delivery and antibacterial abilities in clinic.

Monitoring the intracellular transformation process of surface-cleavable PLGA particles containing disulfide bonds by fluorescence resonance energy transfer

Co-reporter:Dahai Yu, Guangyang Zou, Xiaojing Cui, Zhengwei Mao, Irina Estrela-Lopis, Edwin Donath and Changyou Gao

Journal of Materials Chemistry A 2015 vol. 3(Issue 45) pp:8865-8873

Publication Date(Web):19 Oct 2015

DOI:10.1039/C5TB01687H

A great number of stimuli-responsive particles have been developed and used for biomedical applications such as intracellular drug delivery. It is of paramount importance to study the intracellular responsive process of these particles, offering insight into the understanding of their structure variation and design criteria for better performance. In this study polyethyleneimine (PEI)-coated poly(lactide-co-glycolide) (PLGA) particles with a diameter of 430 nm were prepared via a one-step emulsion method. The amino groups in the PEI molecules allowed further covalent linking of fluorescein isothiocyanate (FITC), bifunctional coupling agents 3,3′-dithiobispropionimidate, amino-ended polyethylene glycol (NH2–PEG–NH2) and tetramethylrhodamine isothiocyanate (TRITC), resulting in fluorescence resonance energy transfer (FRET) pairs on the particles. The particles exhibited glutathione-responsive ability, and lost the FRET effect due to the separation of FITC/TRITC pairs from the particle surface as a result of the cleavage of disulfide bonds. The particles showed different FRET change rates in A549 cells and HEK293 cells depending on the intracellular GSH concentration. Moreover, a much slower degradation rate was found inside cells than in simulated buffer with a similar GSH concentration. The results suggest that the responsive behaviors of the particles obtained in simulated buffer may not match fully/correctly with the real situation in a complicated intracellular environment.

Cell Membrane Capsules for Encapsulation of Chemotherapeutic and Cancer Cell Targeting in Vivo

Co-reporter:Li-Hua Peng, Yuan-Hong Zhang, Li-Jie Han, Chen-Zhen Zhang, Jia-He Wu, Xia-Rong Wang, Jian-Qing Gao, and Zheng-Wei Mao

ACS Applied Materials & Interfaces 2015 Volume 7(Issue 33) pp:18628

Publication Date(Web):August 11, 2015

DOI:10.1021/acsami.5b05065

Systemic administration of chemotherapeutic agents can cause indiscriminate drug distribution and severe toxicity. Until now, encapsulation and targeting of drugs have typically relied on synthetic vehicles, which cannot minimize the clearance by the renal system and may also increase the risk of chemical side effects. Cell membrane capsules (CMCs) provide a generic and far more natural approach to the challenges of drug encapsulation and delivery in vivo. Here aptamer AS1411, which can recognize and bind overexpressed nucleolin on a cancer cell membrane, was chemically conjugated onto CMCs. As a result, AS1411 modified CMCs showed enhanced ingestion in certain cancer cells in vitro and accumulation in mouse cancer xenografts in vivo. Chemotherapeutics and contrast agents with therapeutically significant concentrations can be packaged into CMCs by reversible permeating their plasma membranes. The systematic administration of cancer targeting CMCs loaded with doxorubicin hydrochloride can significantly inhibit tumor growth in mouse xenografts, with significantly reduced toxicity compared to free drug. These findings suggest that cancer targeting CMCs may have considerable benefits in drug delivery and cancer treatment.Keywords: cancer treatment; cell membrane capsules; drug delivery; reversible permeating; targeting

Combinational effect of matrix elasticity and alendronate density on differentiation of rat mesenchymal stem cells

Co-reporter:Pengfei Jiang, Zhengwei Mao, Changyou Gao

Acta Biomaterialia 2015 Volume 19() pp:76-84

Publication Date(Web):June 2015

DOI:10.1016/j.actbio.2015.03.018

Abstract

Differentiation of mesenchymal stem cells (MSCs) is regulated by multivariate physical and chemical signals in a complicated microenvironment. In this study, polymerizable double bonds (GelMA) and osteo-inductive alendronate (Aln) (Aln-GelMA) were sequentially grafted onto gelatin molecules. The biocompatible hydrogels with defined stiffness in the range of 4–40 kPa were prepared by using polyethylene glycol diacrylate (PEGDA) as additional crosslinker. The Aln density was adjusted from 0 to 4 μM by controlling the ratio between the GelMA and Aln-GelMA. The combinational effects of stiffness and Aln density on osteogenic differentiation of MSCs were then studied in terms of ALP activity, collagen type I and osteocalcin expression, and calcium deposition. The results indicated that the stiffness and Aln density could synergistically improve the expression of all these osteogenesis markers. Their osteo-inductive effects are comparable to some extent, and high Aln density could be more effective than the stiffness.

Influence of bovine serum albumin coated poly(lactic-co-glycolic acid) particles on differentiation of mesenchymal stem cells

Co-reporter:Pengfei Jiang, Dahai Yu, Wenjing Zhang, Zhengwei Mao and Changyou Gao

RSC Advances 2015 vol. 5(Issue 51) pp:40924-40931

Publication Date(Web):30 Apr 2015

DOI:10.1039/C5RA07219K

Interaction with colloidal particles may change the structure and function of the cytoskeleton, and influence cell shape and signal pathways, and thereby modulate the differentiation of stem cells. In this study, bovine serum albumin-coated poly(lactic-co-glycolic acid) particles (PLGA–BSA) were prepared and incubated with rat mesenchymal stem cells (MSCs). It was found that they promote osteogenic ALP activity and the expression of collagen type I (COL) and osteocalcin (OCN) of MSCs, but inhibit the expression of adipogenic peroxisome proliferator-activated receptor-gamma (PPARγ) and lipoprotein lipase (LPL) at both mRNA and protein levels. The p38 pathway is altered in the presence of PLGA–BSA particles, which might be responsible for the particle-induced differentiation of MSCs.

A complementary density gradient of zwitterionic polymer brushes and NCAM peptides for selectively controlling directional migration of Schwann cells

Co-reporter:Tanchen Ren, Shan Yu, Zhengwei Mao, Changyou Gao

Biomaterials 2015 56() pp: 58-67

Publication Date(Web):

DOI:10.1016/j.biomaterials.2015.03.052

A quantitative study of the intracellular concentration of graphene/noble metal nanoparticle composites and their cytotoxicity

Co-reporter:Xiangyan Zhou, Marco Dorn, Jürgen Vogt, Daniel Spemann, Wei Yu, Zhengwei Mao, Irina Estrela-Lopis, Edwin Donath and Changyou Gao

Nanoscale 2014 vol. 6(Issue 15) pp:8535-8542

Publication Date(Web):25 Jun 2014

DOI:10.1039/C4NR01763C

Noble-metal nanoparticles (NPs) especially prepared from gold and silver have been combined on the surface of graphene to obtain graphene-based nanocomposites for novel functions in enhanced performance in bio-imaging, cancer detection and therapy. However, little is known about their cellular uptake, especially the intracellular quantity which plays a critical role in determining their functions and safety. Therefore, we prepared covalently conjugated GO/Au and GO/Ag composites by immobilizing Au and Ag nanoparticles on GO sheets pre-functionalized with disulfide bonds, respectively. The cellular uptake of these composites was quantitatively studied by means of an ion beam microscope (IBM) to determine the metal content in human lung cancer cells (A549 cells) and liver hepatocellular carcinoma cells (HepG2 cells). The cell uptake was also studied by inductively coupled plasma mass spectrometry (ICP-MS), which is one of the most sensitive techniques being applied to cell suspensions, for comparison. Toxicity, one of the consequences of cellular uptake of GO based composites, was studied as well. The potential toxicity mechanism was also suggested based on the results of intracellular quantification of the nanomaterials.

Polyelectrolyte Multilayer Patterns Created by Capillary Force and Their Impact on Cell Migration

Co-reporter:Lulu Han;Jindan Wu;Tanchen Ren;Zhengwei Mao;Yang Guo ;Changyou Gao

Chinese Journal of Chemistry 2014 Volume 32( Issue 1) pp:66-72

Publication Date(Web):

DOI:10.1002/cjoc.201300704

Abstract

Cell migration plays a crucial role in a variety of physiological and pathological processes. In this study a method of capillary force lithography was used to treat poly(sodium 4-styrenesulfonate) (PSS)/poly(diallyldimethylammonium) chloride (PDADMAC) multilayers with a PDMS stamp before or after etching by NaCl solution, yielding physical patterns with various features such as double thin lines, double strips, meniscus-shaped ridges, and high ridges. The ridge height is controllable in the range of 25 and 1100 nm. Migration of smooth muscle cells (SMCs) was restrained by the double-line patterns in a ridge height-dependent manner. By contrast, the mobility of SMCs was controlled by both the hydration ratio of the multilayers and the pattern features.

TAT conjugated cationic noble metal nanoparticles for gene delivery to epidermal stem cells

Co-reporter:Li-Hua Peng, Jie Niu, Chen-Zhen Zhang, Wei Yu, Jia-He Wu, Ying-Hui Shan, Xia-Rong Wang, You-Qing Shen, Zheng-Wei Mao, Wen-Quan Liang, Jian-Qing Gao

Biomaterials 2014 35(21) pp: 5605-5618

Publication Date(Web):

DOI:10.1016/j.biomaterials.2014.03.062

Immobilization of Enzymes on 2-Hydroxyethyl Methacrylate and Glycidyl Methacrylate Copolymer Brushes

Co-reporter:Tanchen Ren;Dr. Zhengwei Mao;Dr. Sergio Enrique Moya;Dr. Changyou Gao

Chemistry – An Asian Journal 2014 Volume 9( Issue 8) pp:2132-2139

Publication Date(Web):

DOI:10.1002/asia.201402150

Abstract

The immobilization of enzymes is of paramount importance to maintain their activity and stability. In this study, surface-initiated atom-transfer radical polymerization was applied to prepare poly(2-hydroxyethyl methacrylate)-block-poly(2-hydroxyethyl methacrylate-co-glycidyl methacrylate) brushes on glass slides. The polymerization kinetics was followed by using a quartz crystal microbalance with dissipation monitoring and ellipsometry in terms of mass and thickness growth, respectively. The surface chemical compositions of the obtained polymer brushes were characterized by X-ray photoelectron spectroscopy. Their mass, thickness, and enzyme-immobilization ability could be easily tuned by the initiator reaction time, monomer ratio, and polymerization time. The antibacterial activity and stability of the immobilized lysozymes were studied by fluorescent staining and bacteria lysis assay, which revealed that the lysozymes on the copolymer brushes had good stability during storage at 4 °C for up to 30 days.

Complementary Density Gradient of Poly(hydroxyethyl methacrylate) and YIGSR Selectively Guides Migration of Endotheliocytes

Co-reporter:Tanchen Ren, Shan Yu, Zhengwei Mao, Sergio Enrique Moya, Lulu Han, and Changyou Gao

Biomacromolecules 2014 Volume 15(Issue 6) pp:

Publication Date(Web):May 19, 2014

DOI:10.1021/bm500385n

Selective enhancement of directional migration of endotheliocytes (ECs) over vascular smooth muscle cells (SMCs) plays a significant role for the fast endothelialization of blood-contacting implants, in particular for the antirestenosis of vascular stents. Herein, a complementary density gradient of poly(2-hydroxyethyl methacrylate) (PHEMA) brushes and YIGSR peptide, a sequence specifically improving the mobility of ECs, was fabricated using a dynamically controlled reaction process. The gradients were visualized by fluorescent labeling and further quantified by X-ray photoelectron spectrometry (XPS) and quartz crystal microbalance with dissipation (QCM-d). The ECs exhibited preferential orientation and enhanced directional migration behavior on the gradient surface toward the region of lower PHEMA density and higher YIGSR density. The migration rate of the ECs was significantly enhanced to 5-fold, whereas the mobility of SMCs was not significantly influenced, leading to faster migration of ECs than SMCs. Therefore, the success of the complementary gradient relies on the appropriate interplay between the PHEMA brushes and the cell-specific ligands, enabling the selective guidance of EC migration.

Study of the Selective Uptake Progress of Aptamer-Modified PLGA Particles by Liver Cells

Co-reporter:Dahai Yu;Yuying Zhang;Zhengwei Mao;Changyou Gao

Macromolecular Bioscience 2013 Volume 13( Issue 10) pp:1413-1421

Publication Date(Web):

DOI:10.1002/mabi.201300165

It is of paramount importance to study the cellular uptake processes of particles with defined surface property, especially the uptake pathways and intracellular transportation. In this study, aptamer AS1411 molecules, which are known to specifically bind the over-expressed nucleolin on cancer cell membrane, were conjugated onto bovine serum albumin-decorated poly(D,L-lactide-co-glycolide; PLGA, Φ400 nm) particles with a density of 1–1.7 molecule/10 nm². The aptamer-modified PLGA particles were preferably ingested by liver cancer cells with higher amount and faster rate. The clathrin-mediated endocytosis and macropinocytosis pathways played a more important role in uptake of the aptamer modified particles.

Directional cell migration through cell–cell interaction on polyelectrolyte multilayers with swelling gradients

Co-reporter:Lulu Han, Zhengwei Mao, Jindan Wu, Yang Guo, Tanchen Ren, Changyou Gao

Biomaterials 2013 34(4) pp: 975-984

Publication Date(Web):

DOI:10.1016/j.biomaterials.2012.10.041

Directional Migration of Vascular Smooth Muscle Cells Guided by a Molecule Weight Gradient of Poly(2-hydroxyethyl methacrylate) Brushes

Co-reporter:Tanchen Ren, Zhengwei Mao, Jian Guo, and Changyou Gao

Langmuir 2013 Volume 29(Issue 21) pp:6386-6395

Publication Date(Web):May 1, 2013

DOI:10.1021/la4004609

Directional migration of cells mediated by gradient cues in vitro can mimic the corresponding biological events in vivo and thereby provides a way to disclose the cascade responses in tissue regeneration processes and to develop novel criteria for design of tissue-inductive biomaterials. In this work, a molecular weight gradient of poly(2-hydroxyethyl methacrylate) (PHEMA) brushes with a thickness ranging from 3 to 30 nm and slopes of 0.8–3.2 nm/mm were fabricated by using surface-initiated atom transfer radical polymerization (ATRP) and a dynamically controlled reaction process. The PHEMA gradients were characterized by X-ray photoelectron spectrometry (XPS) and ellipsometry. The adhesion number, spreading area, adhesion force, and expression of focal adhesion and actin fibers of vascular smooth muscle cells (VSMCs) decreased along with the increase of the PHEMA brushes length. The VSMCs exhibited preferential orientation and enhanced directional migration toward the direction of reduced PHEMA thickness, whose extent was dependent on the gradient slope and polymer thickness. Most of the cells were oriented, and 87% of the cells moved directionally at the optimal conditions.

Unidirectional migration of single smooth muscle cells under the synergetic effects of gradient swelling cue and parallel groove patterns

Co-reporter:Lulu Han, Zhengwei Mao, Jindan Wu, Yang Guo, Tanchen Ren, Changyou Gao

Colloids and Surfaces B: Biointerfaces 2013 Volume 111() pp:1-6

Publication Date(Web):1 November 2013

DOI:10.1016/j.colsurfb.2013.05.011

•A swelling gradient is generated on groove patterned surfaces.•The synergetic surface topography and swelling gradient achieves directional migration of single cells.•The cell migration rate is dominated by surface swelling gradient rather than topography.The air-plasma treated poly(dimethylsiloxane) membrane with linear grooves and ridges is alternately assembled with poly(sodium 4-styrenesulfonate) (PSS)/poly(diallyldimethylammonium) chloride (PDADMAC) multilayers, which is then treated in a gradient solution of 3–5 M NaCl, with the pattern direction parallel to the gradient. The synergetic effects of the surface topography and swelling gradient can effectively guide the unidirectional migration of single smooth muscle cells without impairment of their migration rate.

Uptake of hydrogel particles with different stiffness and its influence on HepG2 cell functions

Co-reporter:Weijun Liu, Xiangyan Zhou, Zhengwei Mao, Dahai Yu, Bing Wang and Changyou Gao

Soft Matter 2012 vol. 8(Issue 35) pp:9235-9245

Publication Date(Web):02 Aug 2012

DOI:10.1039/C2SM26001H

The interactions between colloidal particles and cells are of paramount importance for understanding the potential safety issue of the particles, which in turn provide the design principles of various carriers for biomedical applications. In this study, the influence of particle stiffness on cellular uptake and cell functions are elucidated. Four types of poly(2-hydroxyethyl methacrylate) (HEMA) hydrogel particles with different amounts of crosslinking agent, N,N′-methylene-bis-acrylamide (BIS), and thereby compressive modulus (from 15–156 kPa) were synthesized by an emulsion–precipitation polymerization. All of the particles had a diameter of 800–1000 nm in water. Although the softer particles were slightly swollen in the cell culture medium, the particle sizes were still similar. Adsorption of proteins (35 mg g−1 particles) occurred on all the particles, leading to a change of zeta potential from −20 mV (in water) to −5 mV (in serum containing medium). However, the particle size and surface charge property were not significantly changed. The softer particles were internalized by HepG2 cells at a faster rate and larger amount than the stiffer particles. Cellular uptake mechanisms were clarified by the addition of inhibitors to specific endocytosis pathways. The influence of the particle uptake on cell toxicity and functions were then studied in terms of cell viability, morphology and cytoskeleton organization, and cell adhesion. Uptake of all types of the particles did not cause an apparent decrease of cell viability and alteration of cell morphology, but changed the cytoskeleton organization to some extent. The cell adhesion ability was significantly affected, especially after uptake of the stiffer particles.

Controlling the migration behaviors of vascular smooth muscle cells by methoxy poly(ethylene glycol) brushes of different molecular weight and density

Co-reporter:Jindan Wu, Zhengwei Mao, Changyou Gao

Biomaterials 2012 33(3) pp: 810-820

Publication Date(Web):

DOI:10.1016/j.biomaterials.2011.10.022

Preparation and cellular uptake of PLGA particles loaded with lamivudine

Co-reporter:Bing Wang;GuanQun Chen;ZhengWei Mao;YuYing Zhang;DaHai Yu

Science Bulletin 2012 Volume 57( Issue 31) pp:3985-3993

Publication Date(Web):2012 November

DOI:10.1007/s11434-012-5419-1

Poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles loaded with lamivudine and coated with bovine serum albumin (BSA) were prepared via a double emulsion method. The influences of experiments parameters such as volume of inner aqueous phase, concentration of organic phase and ultrasonication time on the particle size and drug entrapment efficiency were investigated, obtaining PLGA particles with a diameter of ∼260 nm and drug entrapment efficiency of ∼35%. The particles were observed by scanning electron microscopy and transmittance electron microscopy, showing a core-shell structure. BCA assay found that 58 mg BSA was present on/in 1 g LPB particles. The loaded lamivudine showed a burst release at beginning and sustained release until 24 h in physiological conditions. Low pH could accelerate the release of lamivudine from PLGA particles, making the PLGA particles potential intelligent intracellular drug carriers. The PLGA particles were readily internalized into the human liver cells within a short time and increased gradually with the prolongation of incubation time regardless of the loading of lamivudine. The particles either resided within lysosomes or transferred to cytoplasm, but could not enter into the cell nucleus. The cell viability was not significantly influenced in the presence of the particles regardless of lamivudine encapsulation, suggesting that this kind of particles may be a good candidate for the intracellular anti-hepatitis B drug delivery.

Influence of Surface Coating of PLGA Particles on the Internalization and Functions of Human Endothelial Cells

Co-reporter:Dahai Yu, Yuying Zhang, Xiangyan Zhou, Zhengwei Mao, and Changyou Gao

Biomacromolecules 2012 Volume 13(Issue 10) pp:

Publication Date(Web):August 27, 2012

DOI:10.1021/bm3010484

This study is focused on the uptake of PLGA particles with different coatings and its influences on the functions and toxicity of human endothelial cells. The PLGA particles coated with polyethyleneimine (PEI) or bovine serum albumin (BSA) were prepared via a one-step emulsion method, which had a similar diameter of ∼420 nm in water and ∼170 nm in a dry state but oppositely charged surfaces. Both types of the particles were readily internalized into cells within a short time regardless of their surface chemistry. Uptake of the positively charged particles caused apparently a decrease in cell viability, but did not significantly influence mitochondrial membrane potential and activity of caspase-3. The cell adhesion and migration were significantly affected, especially after uptake of the PLGA-PEI particles. The secretion levels of von Willebrand factor (vWF) and 6-k-PGF1α were not significantly influenced regardless of the surface coating.

THE ANNUAL MEETING OF THE NATIONAL ACADEMY OF SCIENCES

Co-reporter:

Science 1918 Vol 47(1217) pp:419-420

Publication Date(Web):26 Apr 1918

DOI:10.1126/science.47.1217.419-a

UNIVERSITY AND EDUCATIONAL NEWS

Co-reporter:

Science 1918 Vol 48(1249) pp:572-573

Publication Date(Web):06 Dec 1918

DOI:10.1126/science.48.1249.572

Monitoring the intracellular transformation process of surface-cleavable PLGA particles containing disulfide bonds by fluorescence resonance energy transfer

Co-reporter:Dahai Yu, Guangyang Zou, Xiaojing Cui, Zhengwei Mao, Irina Estrela-Lopis, Edwin Donath and Changyou Gao