Yong-Kuan Gong - Cochemist

Cell membrane mimetic coating immobilized by mussel-inspired adhesion on commercial ultrafiltration membrane to enhance antifouling performance

Co-reporter:Qi Xue, Hao Cao, Fanning Meng, Miao Quan, Yong-Kuan Gong

Journal of Membrane Science 2017 Volume 528(Volume 528) pp:

Publication Date(Web):15 April 2017

DOI:10.1016/j.memsci.2017.01.009

•Cell membrane antifouling and mussel adhesion are assembled in copolymer PMEND.•PMEND assembled into antifouling film on separation membrane by self-adhesion.•Polydopamine mediate layer can enhance the density and stability of PMEND coating.•Excellent antifouling membranes can be produced in large scale by PMEND dip coating.A facile method of modifying commercial polyethersulfone ultrafiltration membrane (PESUM) was developed based on mussel adhesive mimetic polydopamine (PDA) and cell membrane antifouling phosphorylcholine (PC). The PESUM was firstly coated with a thin PDA layer to confer the membrane adhesive property. A cell membrane mimetic and mussel adhesive mimetic random copolymer (PMEND) bearing both antifouling PC zwitterions and adhesive dopamine groups at different side chains was then immobilized onto the PDA surface by dopamine adhesion from the aqueous solution. The immobilized PMEND spontaneously formed a cell outer membrane mimetic film on the PESUM/PDA surface, which was stable in air, gasoline and pH 3–10 water for more than 2-weeks. Importantly, the water flux of this PESUM/PDA/PMEND membrane could be recovered up to 100% and 93% after one and three cycles of fouling by 1.0 mg/mL BSA solution ultrafiltration, respectively. More importantly, the modified membrane could remove more than 99.99% of oil from an 80,000 ppm gasoline/water emulsion. Furthermore, this PDA mediated cell outer membrane mimetic modification strategy is substrate independent and can be applied to other membranes and surfaces to enhance antifouling performance.Download high-res image (260KB)Download full-size image

Quantitative fabrication, performance optimization and comparison of PEG and zwitterionic polymer antifouling coatings

Co-reporter:Cheng-Mei Xing, Fan-Ning Meng, Miao Quan, Kai Ding, ... Yong-Kuan Gong

Acta Biomaterialia 2017 Volume 59(Volume 59) pp:

Publication Date(Web):1 September 2017

DOI:10.1016/j.actbio.2017.06.034

A versatile fabrication and performance optimization strategy of PEG and zwitterionic polymer coatings is developed on the sensor chip of surface plasma resonance (SPR) instrument. A random copolymer bearing phosphorylcholine zwitterion and active ester side chains (PMEN) and carboxylic PEG coatings with comparable thicknesses were deposited on SPR sensor chips via amidation coupling on the precoated polydopamine (PDA) intermediate layer. The PMEN coating showed much stronger resistance to bovine serum albumin (BSA) adsorption than PEG coating at very thin thickness ( ∼ 1 nm). However, the BSA resistant efficacy of PEG coating could exceed that of PMEN due to stronger steric repelling effect when the thickness increased to 1.5∼3.3 nm. Interestingly, both the PEG and PMEN thick coatings (≈3.6 nm) showed ultralow fouling by BSA and bovine plasma fibrinogen (Fg). Moreover, changes in the PEG end group from –OH to –COOH, protein adsorption amount could increase by 10-fold. Importantly, the optimized PMEN and PEG-OH coatings were easily duplicated on other substrates due to universal adhesion of the PDA layer, showed excellent resistance to platelet, bacteria and proteins, and no significant difference in the antifouling performances was observed. These detailed results can explain the reported discrepancy in performances between PEG and zwitterionic polymer coatings by thickness. This facile and substrate-independent coating strategy may benefit the design and manufacture of advanced antifouling biomedical devices and long circulating nanocarriers.Statement of SignificancePrevention of biofouling is one of the biggest challenges for all biomedical applications. However, it is very difficult to fabricate a highly hydrophilic antifouling coating on inert materials or large devices. In this study, PEG and zwitterion polymers, the most widely investigated polymers with best antifouling performance, are conveniently immobilized on different kinds of substrates from their aqueous solutions by precoating a polydopamine intermediate layer as the universal adhesive and readily re-modifiable surface. Importantly, the coating fabrication and antifouling performance can be monitored and optimized quantitatively by a surface plasma resonance (SPR) system. More significantly, the SPR on-line optimized coatings were successfully duplicated off-line on other substrates, and supported by their excellent antifouling properties.Download high-res image (75KB)Download full-size image

Anti-phagocytosis and tumor cell targeting micelles prepared from multifunctional cell membrane mimetic polymers

Co-reporter:Hai-Tao Jiang, Kai Ding, Fan-Ning Meng, Li-Li Bao, Yu-Dong Chai and Yong-Kuan Gong

Journal of Materials Chemistry A 2016 vol. 4(Issue 32) pp:5464-5474

Publication Date(Web):25 Jul 2016

DOI:10.1039/C6TB00953K

Phagocytic clearance and inefficient targeting are two major concerns for nanomedicines in cancer therapy. In this study, cell membrane inspired multifunctional copolymers (PMNCFs) were synthesized by a combination of cell membrane stealthy hydrophilic phosphorylcholine (PC), hydrophobic cholesterol (Chol) and tumor targeting folic acid (FA) functionalities on the different side chain ends. PMNCF micelles were prepared in aqueous solution to form a cell membrane mimetic structure with linked folic acid ligands as the protruding antennae on the surface of the micelles. Coumarin-6 loaded PMNCF micelles indicated that the mouse peritoneal macrophage cell uptake efficiency was suppressed to 1/10 compared with that of PLA nanoparticles. Doxorubicin loaded micelle measurements demonstrated that up to 30% of the drug could be obtained forming a stable formulation under both storage and physiological conditions. Tumor cell uptake and toxicity studies revealed that FA-decorated PMNCF micelles could increase MADB-106 cell uptake by 4-fold, and DOX loaded PMNCF micelles could kill tumor cells more efficiently than the same amount of free DOX. These exciting results confirmed the great potential of the stable, stealthy and tumor cell targeting PMNCF micelles for developing advanced long circulation and target-selective drug delivery nanoparticles.

Substrate independent coating formation and anti-biofouling performance improvement of mussel inspired polydopamine

Co-reporter:Yuan Dang, Cheng-Mei Xing, Miao Quan, Yan-Bing Wang, Shi-Ping Zhang, Su-Qing Shi and Yong-Kuan Gong

Journal of Materials Chemistry A 2015 vol. 3(Issue 20) pp:4181-4190

Publication Date(Web):15 Apr 2015

DOI:10.1039/C5TB00341E

Mussel inspired polydopamine (PDA) coating has been proven to be a simple and effective method for surface modification of biomaterials. However, the adhesive functional groups remaining on the surface of PDA coating may promote the attachment of nonspecific proteins and microorganisms and hinder anti-biofouling performance. In this study, the PDA coating formation process is monitored in real-time by a sensitive surface plasmon resonance (SPR) technique at different pH values, initial dopamine concentrations and deposition times. The coating morphology is observed by atomic force microscopy (AFM). Nonspecific protein adsorption, platelet and fibroblast cell adhesion, as well as bacteria attachment on the PDA coatings of different thicknesses are measured to evaluate their anti-biofouling performance. Thickness-dependent biofouling of the PDA coatings is demonstrated by the accumulation of adhesive functional groups within the PDA matrix. In order to reduce the biofouling, we treat the PDA coating by FeCl3 coordination, NaIO4 oxidation, heating in air and grafting with a phosphorylcholine copolymer bearing active ester groups. The modified surfaces are characterized by X-ray photoelectron spectroscopy (XPS) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy measurements. Interestingly, all the treatments help to resist protein adsorption significantly. More excitingly, the simple grafting strategy with a phosphorylcholine copolymer can resist more than 99% of platelet, fibroblast, and bacteria cell attachment, 98% of bovine serum albumin and 95% of bovine plasma fibrinogen adsorption on the PDA coating. These results may find applications in the vast area of surface antifouling, especially for most biomedical devices.

Biocompatible and antifouling coating of cell membrane phosphorylcholine and mussel catechol modified multi-arm PEGs

Co-reporter:Yuan Dang, Miao Quan, Cheng-Mei Xing, Yan-Bing Wang and Yong-Kuan Gong

Journal of Materials Chemistry A 2015 vol. 3(Issue 11) pp:2350-2361

Publication Date(Web):28 Jan 2015

DOI:10.1039/C4TB02140A

The design and easy fabrication of biocompatible and antifouling coatings on different materials are extremely important for biotechnological and biomedical devices. Here we report a substrate-independent biomimetic modification strategy for fabricating a biocompatible and antifouling ultra-thin coating. Cell membrane antifouling phosphorylcholine (PC) and/or mussel adhesive catechol (c) groups are grafted at the amino-ends of an 8-armed poly(ethylene glycol). The PC groups are introduced by grafting a random copolymer bearing both PC and active ester groups. The modified 8-arm PEGs (PEG-2c-23PC, PEG-6c-23PC and PEG-8c) anchor themselves onto various substrates from aqueous solution and form cell outer membrane mimetic surfaces. Static contact angle, atomic force microscope (AFM) and X-ray photoelectron spectra (XPS) measurements confirm the successful fabrication of coatings on polydopamine (PDA) precoated surfaces. Real-time interaction results between proteins/bacteria and the coatings measured by surface plasmon resonance (SPR) technique suggest excellent anti-protein adsorption and short-term anti-bacteria adhesion performance. The long-term bacteria adhesion, platelet and L929 cell attachment results strongly support the SPR conclusions. Furthermore, the cell membrane mimetic and mussel adhesive protein mimetic PEG-2c-23PC shows hardly any toxicity to L929 fibroblasts, and the coating surface demonstrates the best anti-biofouling performance. This PDA-assisted immobilization of PC and/or catechol modified multi-arm PEGs provides a convenient and universal way to produce a biocompatible and fouling-resistant surface with tailor-made functions, which hopefully can be expanded to a wider range of applications based on both structure and surface superiorities.

Probing the Adjustments of Macromolecules during Their Surface Adsorption

Co-reporter:Pengxiang Jia, Min He, Yongkuan Gong, Xiao Chu, Jingfa Yang, and Jiang Zhao

ACS Applied Materials & Interfaces 2015 Volume 7(Issue 12) pp:6422

Publication Date(Web):March 11, 2015

DOI:10.1021/acsami.5b01138

Thiol-terminated polymers poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC-SH), poly(N,N-isopropylacrylamide) (PNIPAM-SH), and poly(tert-butyl acrylate) (PtBA-SH) were synthesized, and the polymers were grafted on the gold surfaces of quartz crystal microbalance with dissipation (QCM-D) and surface plasmon resonance (SPR) sensor chips to form brushes. The grafting process of the polymer brushes as well as protein adsorption onto the brush layers was monitored by in situ QCM-D and SPR techniques. By examining the changes in frequency and dissipation factor as well as the value of ∂D/∂f from QCM-D measurements, different stages of the polymer grafting and protein adsorption are distinguished. The most interesting discovery is the conformation change of BSA protein adsorption from a weakly adsorbed native state to a strongly immobilized denatured state on the polymer brushes. The corresponding change in BSA adsorption from a reversible state to an irreversible state was confirmed by SPR measurements. The adsorption of protein on the polymer brushes’ surface relies largely on interaction between the protein and the polymers, and the stronger hydrophilicity of the surfaces is proved to be more effective to suppress the protein adsorption. Analysis of the D–f plot of QCM-D measurements helps to characterize different binding strength of protein and the underlying polymer surface.Keywords: conformation; polymer brushes; protein adsorption; QCM-D; SPR

Long circulating micelles of an amphiphilic random copolymer bearing cell outer membrane phosphorylcholine zwitterions

Co-reporter:Jing Zhao, Yu-Dong Chai, Jing Zhang, Peng-Fei Huang, Kenichi Nakashima, Yong-Kuan Gong

Acta Biomaterialia 2015 Volume 16() pp:94-102

Publication Date(Web):1 April 2015

DOI:10.1016/j.actbio.2015.01.019

Abstract

Polymeric micelles with cell outer membrane mimetic structure were prepared in water from amphiphilic random copolymers bearing both the hydrophilic phosphorylcholine zwitterions and hydrophobic octadecyl side chains of cell outer membrane. The polymeric micelles showed sizes ranging from 80 nm to 120 nm in hydrodynamic diameter and zeta-potentials from −6.4 mV to −2.4 mV by dynamic light scattering measurements. The micelles loaded with 6-coumarin as a fluorescence probe were stable to investigate their blood circulation and biodistribution. The in vitro phagocytosis results using murine peritoneal macrophages showed 10-fold reduction compared with a reference micelle. The in vivo blood circulation half-life of the polymeric micelles following intravenous administration in New Zealand Rabbits was increased from 0.55 h to 90.5 h. More interestingly, tissue distribution results showed that the concentration of the micelles in the kidney is 4-fold higher than that in the liver and other organs 48 h after administration. The results of this work show great promise for designing more effective stealth drug carriers that can minimize reticuloendothelial system clearance and circulate for long time to reach target by using simple cell membrane mimetic random copolymer micelles.

Surface reconstruction and hemocompatibility improvement of a phosphorylcholine end-capped poly(butylene succinate) coating

Co-reporter:Ni Hao;Yan-Bing Wang;Shi-Ping Zhang;Su-Qing Shi;Kenichi Nakashima

Journal of Biomedical Materials Research Part A 2014 Volume 102( Issue 9) pp:2972-2981

Publication Date(Web):

DOI:10.1002/jbm.a.34967

Abstract

Control over cell–material surface interactions is the key to many new and improved biomedical devices. In this study, we present a simple yet effective surface modification method that allows for the surface reconstruction and formation of cell outer membrane mimetic structure on coatings that have significantly increased hemocompatibility. To achieve this, a phosphorylcholine end-capped poly(butylene succinate) (PBS-PC) was synthesized and dip-coated on coverslips. The surface structure of the amphiphilic PBS-PC film was reconstructed by heating in a vacuum oven to obtain the less hydrophilic surface and by immersing in hot water to obtain the more hydrophilic surface. Significant changes in the surface element concentration were observed by X-ray photoelectron spectroscopy analysis and changes in surface wettability were measured by sensitive dynamic contact angle technique. Scanning electron microscope images showed different morphologies of the reconstructed surfaces. Interestingly, the reconstruction between the less hydrophilic and more hydrophilic surfaces is reversible. More importantly, both the reconstructed surfaces are stable in room condition for more than 6 months, and both the surfaces show significant improvement in hemocompatibility as revealed by protein adsorption and platelet adhesion measurements. This reversible surface reconstruction strategy and the interesting results may be significant for fabricating stable and hemocompatible surfaces on differently shaped biomedical devices. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2972–2981, 2014.

Cell membrane mimetic films immobilized by synergistic grafting and crosslinking

Co-reporter:Ming Gong, Yuan Dang, Yan-Bing Wang, Shan Yang, Françoise M. Winnik and Yong-Kuan Gong

Soft Matter 2013 vol. 9(Issue 17) pp:4501-4508

Publication Date(Web):21 Mar 2013

DOI:10.1039/C3SM00086A

Blood compatibility is a critical requirement for materials to be used in medical applications. We describe here a simple and robust method to enhance the biocompatibility of chitosan (CS) surfaces, using random copolymers (PMT) of 2-methacryloyloxyethyl phosphorylcholine (MPC) and trimethoxysilylpropyl methacrylate (TSMA, 6, 14, and 25 mol%) synthesized by free radical copolymerization. The copolymers dissolved in methanol were dip-coated on CS films. The PMT coatings were anchored on CS surfaces during the coating process by covalent bonding of the trimethoxysilane groups with surface amine and/or hydroxyl groups of CS. The composite films were stabilized by crosslinking of the copolymers via amine-catalyzed reactions of the trimethoxysilane groups and further heating (110 °C). Analysis of the PMT-modified CS surfaces by X-ray photoelectron spectroscopy and contact angle measurements indicated that the zwitterionic PC groups were located on or near the film outer surface, which mimics the structure of the cell outer membrane. Film stability studies indicated that PMT copolymers containing 14 mol% TSMA units were linked permanently to CS, whereas PMTs of lower TSMA content were released from the films upon prolonged soaking in water. The CS-PMT (14% TSMA) composite films possessed excellent hemocompatibility, as confirmed by a 60% decrease in protein (bovine serum albumin or fibrinogen) adsorption and a 96% suppression of platelet adhesion, compared to CS films. This simple and stable coating strategy should be useful in a variety of biomedical applications including drug delivery, tissue engineering, stent coatings, and implantable medical devices.

Improved biocompatibility of phosphorylcholine end-capped poly(butylene succinate)

Co-reporter:ShiPing Zhang;LiLi Wang;Shan Yang;YongKuan Gong

Science China Chemistry 2013 Volume 56( Issue 2) pp:174-180

Publication Date(Web):2013 February

DOI:10.1007/s11426-012-4759-7

In this work, the biocompatibility of a biomimetic, fully biodegradable ionomer phosphorylcholine (PC)-functionalized poly(butylene succinate) (PBS-PC) was investigated by means of hemolysis, platelet adhesion, protein adsorption and cytotoxicity experiments. The reference materials were poly(butylene succinate) (PBS) and chloroethylphosphoryl functionalized poly(butylene succinate) (PBS-Cl). The hemolysis rates (HR) of the leaching solutions of PBS, PBS-Cl and PBS-PC were all lower than the safe value, and the rate of PBS-PC was reduced to 1.07%. Scanning electron microscopy (SEM) measurements showed that platelet adhesion and aggregation were significant on both PBS and PBS-Cl surface. In contrast, very few platelets were observed on PBS-PC surface. Bicinchoninic acid (BCA) measurements revealed that the adsorption amounts of bovine serum albumin (BSA) and bovine plasma fibrinogen (BPF) on PBS-PC surface were 52% and 72% reduction respectively compared with those on PBS surface. Moreover, non-cytotoxicity of both PBS-PC particles and its leaching solution was suggested by MTT assay using mouse L929 fibroblast cells. All the results demonstrated that the biocompatibility of PBS could be greatly improved by PC end-capping strategy. This PC functionalized polyester may have potential applications in biological environments as a novel carrier for controlled drug release and scaffold for tissue engineering.

Strategies in biomimetic surface engineering of nanoparticles for biomedical applications

Co-reporter:Yong-kuan Gong and Françoise M. Winnik

Nanoscale 2012 vol. 4(Issue 2) pp:360-368

Publication Date(Web):02 Dec 2011

DOI:10.1039/C1NR11297J

Engineered nanoparticles (NPs) play an increasingly important role in biomedical sciences and in nanomedicine. Yet, in spite of significant advances, it remains difficult to construct drug-loaded NPs with precisely defined therapeutic effects, in terms of release time and spatial targeting. The body is a highly complex system that imposes multiple physiological and cellular barriers to foreign objects. Upon injection in the blood stream or following oral administation, NPs have to bypass numerous barriers prior to reaching their intended target. A particularly successful design strategy consists in masking the NP to the biological environment by covering it with an outer surface mimicking the composition and functionality of the cell’s external membrane. This review describes this biomimetic approach. First, we outline key features of the composition and function of the cell membrane. Then, we present recent developments in the fabrication of molecules that mimic biomolecules present on the cell membrane, such as proteins, peptides, and carbohydrates. We present effective strategies to link such bioactive molecules to the NPs surface and we highlight the power of this approach by presenting some exciting examples of biomimetically engineered NPs useful for multimodal diagnostics and for target-specific drug/gene delivery applications. Finally, critical directions for future research and applications of biomimetic NPs are suggested to the readers.

Doubly Biomimetic Catecholic Phosphorylcholine Copolymer: A Platform Strategy for Fabricating Antifouling Surfaces

Co-reporter:Yong-Kuan Gong;Li-Ping Liu;Phillip B. Messersmith

Macromolecular Bioscience 2012 Volume 12( Issue 7) pp:979-985

Publication Date(Web):

DOI:10.1002/mabi.201200074

Fabrication of cell outer membrane mimetic polymer brush on polysulfone surface via RAFT technique

Co-reporter:Qian Ma, Hui Zhang, Jiang Zhao, Yong-Kuan Gong

Applied Surface Science 2012 Volume 258(Issue 24) pp:9711-9717

Publication Date(Web):1 October 2012

DOI:10.1016/j.apsusc.2012.06.017

Abstract

Cell membrane mimetic antifouling polymer brush was grown on polysulfone (PSF) membrane by surface-induced reversible addition–fragmentation chain transfer (RAFT) polymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC). The RAFT agent immobilized PSF substrate was prepared by successive chloromethylation, amination with ethylenediamine (EDA) and amidation of the amine group of grafted EDA with the carboxylic group of 4-cyanopentanoic acid dithiobenzoate (CPAD). The surface RAFT polymerization of MPC was initiated in aqueous solution by 4,4′-azobis-4-cyanopentanoic acid (ACPA). The formation of PMPC brush coating is evidenced by X-ray photoelectron spectroscopy and water contact angle measurements. The degree of polymerization of PMPC and the polymer grafting density were calculated from the high resolution XPS spectra. The platelet adhesion and protein adsorption results showed that the PMPC-grafted PSF surface has excellent antifouling ability to resist platelet adhesion completely and suppress protein adsorption significantly. This biomimetic and bio-friendly surface RAFT polymerization strategy could be promising for a variety of biomedical applications.

Fabrication and biocompatibility of cell outer membrane mimetic surfaces

Co-reporter:Ming-ming Zong 宫永宽

Chinese Journal of Polymer Science 2011 Volume 29( Issue 1) pp:53-64

Publication Date(Web):2011 January

DOI:10.1007/s10118-010-1019-1

The surface design used for improving biocompatibility is one of the most important issues for the fabrication of medical devices. For mimicking the ideal surface structure of cell outer membrane, a large number of polymers bearing phosphorylcholine (PC) groups have been employed to modify the surfaces of biomaterials and medical devices. It has been demonstrated that the biocompatibility of the modified materials whose surface is required to interact with a living organism has been obviously improved by introducing PC groups. In this review, the fabrication strategies of cell outer membrane mimetic surfaces and their resulted biocompatibilities were summarized.

Fabrication and hemocompatibility of cell outer membrane mimetic surfaces on chitosan by layer by layer assembly with polyanion bearing phosphorylcholine groups

Co-reporter:Ming Gong, Yan-Bing Wang, Ming Li, Bi-Huang Hu, Yong-Kuan Gong

Colloids and Surfaces B: Biointerfaces 2011 Volume 85(Issue 1) pp:48-55

Publication Date(Web):15 June 2011

DOI:10.1016/j.colsurfb.2010.10.049

Three random copolymers poly(2-methacryloyloxyethyl phosphorylcholine-co-methacrylic acid) (PMAs) were synthesized by free radical polymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) and methacrylic acid (MA) with different monomer ratios under monomer-starved conditions. The synthesized PMA polyanions were assembled on chitosan (CS) film surfaces via electrostatic interactions. Using layer by layer (LbL) assembly with PMA polyanion and chitosan polycation, PMA/CS multilayer thin films with phosphorylcholine groups on the outer surfaces were fabricated. The modified surfaces were characterized by dynamic contact angle (DCA), X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). Hemocompatibility of the surfaces was estimated by protein adsorption and platelet adhesion measurements. The results indicated that cell outer membrane mimetic structures were formed on the modified surfaces with PMA as the outermost layer, and the hemocompatibility of the modified surfaces was significantly improved. This facile method of fabricating cell outer membrane mimetic surfaces may have potential applications in the fields of hemocompatible coatings, drug delivery, and tissue engineering.Graphical abstractResearch highlights▶ A facile method of fabricating cell outer membrane mimetic surfaces was developed. ▶ Polyanions bearing phosphorylcholine groups were synthesized. ▶ The polyanions were assembled on chitosan surfaces by electrostatic attraction. ▶ Protein adsorption and platelet adhesion were remarkably suppressed after modification.

Cobalt Porphyrins Immobilized on Polymer Microspheres as Catalysts for the Oxidation of 2-naphthol to 2-hydroxy-1,4-naphthoquinone by Molecular Oxygen

Co-reporter:Jing Zhao;Bao-jiao Gao

Catalysis Letters 2011 Volume 141( Issue 12) pp:1808-1813

Publication Date(Web):2011 December

DOI:10.1007/s10562-011-0703-2

Three types of porous polymer microspheres immobilized with cobalt porphyrins appending p–H, p-Cl and p-NO2 phenyl substituents (designated as CoPP-GMA/MMA, CoCPP-GMA/MMA and CoNPP-GMA/MMA, respectively) were prepared. Their catalytic activities on the oxidation of 2-naphthol to 2-hydroxy-1,4-naphthoquinone by molecular oxygen were investigated in alkaline methanol. The experimental results showed that the porous microsphere supported cobalt porphyrin catalysts could effectively activate molecular oxygen, and 2-naphthol was selectively oxidized to 2-hydroxy-1,4-naphthoquinone with high conversion in alkaline methanol. A phenomenon of distance-dependent catalytic activity was observed and a critical distance of 3.8 nm between porphyrins was determined for the porous polymer microsphere supported catalyst. More interestingly, the activity of the recycled catalyst increased gradually with the increased times of reuse. These results may be helpful in designing highly efficient metalloporphyrin catalysts.

Cell outer membrane mimetic modification of a cross-linked chitosan surface to improve its hemocompatibility

Co-reporter:Peng-bo Huangfu, Ming Gong, Cunfu Zhang, Shan Yang, Jiang Zhao, Yong-kuan Gong

Colloids and Surfaces B: Biointerfaces 2009 Volume 71(Issue 2) pp:268-274

Publication Date(Web):1 July 2009

DOI:10.1016/j.colsurfb.2009.02.014

A novel strategy has been developed to improve the hemocompatibility of chitosan surface by cell outer membrane mimetic structure able to reduce protein adsorption and cell adhesion. Phosphorylcholine dichloride was synthesized and grafted onto a glutaraldehyde-cross-linked chitosan (CS-GA) film surface to prepare phosphorylcholine-coated CS-GA film (CS-GA-PC) through a heterogeneous reaction process. The spectroscopic and contact angle characterization show that a cell outer membrane mimetic structure was formed on the cross-linked chitosan surface, and the significantly improved hemocompatibility of the modified surface was shown by a suppression of 94% on platelet adhesion, a suppression of 60–70% for bovine plasma fibrinogen and bovine serum albumin adsorptions. These results demonstrated that this cell outer membrane mimetic surface modification with phosphorylcholine dichloride is a promising strategy to improve the hemocompatibility of chitosan.

Group reorientation and migration of amphiphilic polymer bearing phosphorylcholine functionalities on surface of cellular membrane mimicking coating

Co-reporter:Shan Yang;Shi-Ping Zhang;Françoise M. Winnik;Fackson Mwale

Journal of Biomedical Materials Research Part A 2008 Volume 84A( Issue 3) pp:837-841

Publication Date(Web):

DOI:10.1002/jbm.a.31418

Abstract

Amphiphilic polymers bearing phosphorylcholine (PC) groups can form films of interfacial structure similar to that of the outer membrane of living cells. The films, as prepared, present PC groups to the external aqueous environment and exhibit good biocompatibility. However, under certain conditions, the surface structure can change irreversibly due to the reorientation and deep migration of the surface groups. X-ray photoelectron spectroscopy (XPS), dynamic contact angle measurements, and cell culture experiments were used to investigate the reorientation and migration of the surface groups of an amphiphilic PC-polymer coating. When the polymer surface is immersed into or drawn out of water, significant reorientation and group migration occurs, as suggested by the large difference between the advancing and receding contact angles. Angle-resolved XPS measurements indicate that the hydrophobic groups move to the air/film interface while the hydrophilic groups migrate towards the bulk of the polymer coating. Long periods of aging may result in irreversible changes of the surface structure and decrease the biocompatibility of the materials. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008

Tunable cell membrane mimetic surfaces prepared with a novel phospholipid polymer

Co-reporter:Ming Gong, Shan Yang, Jia-ni Ma, Shi-ping Zhang, Françoise M. Winnik, Yong-kuan Gong

Applied Surface Science 2008 Volume 255(Issue 2) pp:555-558

Publication Date(Web):15 November 2008

DOI:10.1016/j.apsusc.2008.06.148

Abstract

A novel method to fabricate and tune cell membrane mimetic surfaces was developed based on the use of an amphiphilic random copolymer bearing phosphorylcholine (PC), stearyl and crosslinkable trimethoxysilylpropyl groups synthesized by free radical copolymerization. The polymer was coated on glass coverslips by dip-coating. The coated films were treated in water allowing reorganization of the surface groups to mimic the structure of cell outer membranes. This structure was fixed by crosslinking of the trimethoxysilylpropyl groups linked to the copolymer chains, as ascertained by dynamic contact angle (DCA) and attenuated total reflectance infrared spectroscopy (ATR-FTIR) measurements. Our results indicate that the surface structure can be tuned to a great extent to obtain a stable outer membrane mimetic surface/interface.

Biocompatible and antifouling coating of cell membrane phosphorylcholine and mussel catechol modified multi-arm PEGs

Co-reporter:Yuan Dang, Miao Quan, Cheng-Mei Xing, Yan-Bing Wang and Yong-Kuan Gong

Journal of Materials Chemistry A 2015 - vol. 3(Issue 11) pp:NaN2361-2361

Publication Date(Web):2015/01/28

DOI:10.1039/C4TB02140A

The design and easy fabrication of biocompatible and antifouling coatings on different materials are extremely important for biotechnological and biomedical devices. Here we report a substrate-independent biomimetic modification strategy for fabricating a biocompatible and antifouling ultra-thin coating. Cell membrane antifouling phosphorylcholine (PC) and/or mussel adhesive catechol (c) groups are grafted at the amino-ends of an 8-armed poly(ethylene glycol). The PC groups are introduced by grafting a random copolymer bearing both PC and active ester groups. The modified 8-arm PEGs (PEG-2c-23PC, PEG-6c-23PC and PEG-8c) anchor themselves onto various substrates from aqueous solution and form cell outer membrane mimetic surfaces. Static contact angle, atomic force microscope (AFM) and X-ray photoelectron spectra (XPS) measurements confirm the successful fabrication of coatings on polydopamine (PDA) precoated surfaces. Real-time interaction results between proteins/bacteria and the coatings measured by surface plasmon resonance (SPR) technique suggest excellent anti-protein adsorption and short-term anti-bacteria adhesion performance. The long-term bacteria adhesion, platelet and L929 cell attachment results strongly support the SPR conclusions. Furthermore, the cell membrane mimetic and mussel adhesive protein mimetic PEG-2c-23PC shows hardly any toxicity to L929 fibroblasts, and the coating surface demonstrates the best anti-biofouling performance. This PDA-assisted immobilization of PC and/or catechol modified multi-arm PEGs provides a convenient and universal way to produce a biocompatible and fouling-resistant surface with tailor-made functions, which hopefully can be expanded to a wider range of applications based on both structure and surface superiorities.

Anti-phagocytosis and tumor cell targeting micelles prepared from multifunctional cell membrane mimetic polymers

Co-reporter:Hai-Tao Jiang, Kai Ding, Fan-Ning Meng, Li-Li Bao, Yu-Dong Chai and Yong-Kuan Gong

Journal of Materials Chemistry A 2016 - vol. 4(Issue 32) pp:NaN5474-5474

Publication Date(Web):2016/07/25

DOI:10.1039/C6TB00953K

Phagocytic clearance and inefficient targeting are two major concerns for nanomedicines in cancer therapy. In this study, cell membrane inspired multifunctional copolymers (PMNCFs) were synthesized by a combination of cell membrane stealthy hydrophilic phosphorylcholine (PC), hydrophobic cholesterol (Chol) and tumor targeting folic acid (FA) functionalities on the different side chain ends. PMNCF micelles were prepared in aqueous solution to form a cell membrane mimetic structure with linked folic acid ligands as the protruding antennae on the surface of the micelles. Coumarin-6 loaded PMNCF micelles indicated that the mouse peritoneal macrophage cell uptake efficiency was suppressed to 1/10 compared with that of PLA nanoparticles. Doxorubicin loaded micelle measurements demonstrated that up to 30% of the drug could be obtained forming a stable formulation under both storage and physiological conditions. Tumor cell uptake and toxicity studies revealed that FA-decorated PMNCF micelles could increase MADB-106 cell uptake by 4-fold, and DOX loaded PMNCF micelles could kill tumor cells more efficiently than the same amount of free DOX. These exciting results confirmed the great potential of the stable, stealthy and tumor cell targeting PMNCF micelles for developing advanced long circulation and target-selective drug delivery nanoparticles.

Substrate independent coating formation and anti-biofouling performance improvement of mussel inspired polydopamine

Co-reporter:Yuan Dang, Cheng-Mei Xing, Miao Quan, Yan-Bing Wang, Shi-Ping Zhang, Su-Qing Shi and Yong-Kuan Gong

Journal of Materials Chemistry A 2015 - vol. 3(Issue 20) pp:NaN4190-4190

Publication Date(Web):2015/04/15

DOI:10.1039/C5TB00341E

Mussel inspired polydopamine (PDA) coating has been proven to be a simple and effective method for surface modification of biomaterials. However, the adhesive functional groups remaining on the surface of PDA coating may promote the attachment of nonspecific proteins and microorganisms and hinder anti-biofouling performance. In this study, the PDA coating formation process is monitored in real-time by a sensitive surface plasmon resonance (SPR) technique at different pH values, initial dopamine concentrations and deposition times. The coating morphology is observed by atomic force microscopy (AFM). Nonspecific protein adsorption, platelet and fibroblast cell adhesion, as well as bacteria attachment on the PDA coatings of different thicknesses are measured to evaluate their anti-biofouling performance. Thickness-dependent biofouling of the PDA coatings is demonstrated by the accumulation of adhesive functional groups within the PDA matrix. In order to reduce the biofouling, we treat the PDA coating by FeCl3 coordination, NaIO4 oxidation, heating in air and grafting with a phosphorylcholine copolymer bearing active ester groups. The modified surfaces are characterized by X-ray photoelectron spectroscopy (XPS) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy measurements. Interestingly, all the treatments help to resist protein adsorption significantly. More excitingly, the simple grafting strategy with a phosphorylcholine copolymer can resist more than 99% of platelet, fibroblast, and bacteria cell attachment, 98% of bovine serum albumin and 95% of bovine plasma fibrinogen adsorption on the PDA coating. These results may find applications in the vast area of surface antifouling, especially for most biomedical devices.