Folate Ligand Orientation Optimized during Cell Membrane Mimetic Micelle Formation for Enhanced Tumor Cell Targeting.

Nanocarriers with strong tumor cell targeting ability have been expected to overcome limitations of cancer chemotherapy. Herein, cell membrane mimetic micelles were prepared from a random copolymer (PMNCF) containing cell membrane phosphorylcholine zwitterion, cholesterol, and tumor cell targeting folic acid (FA) at the side chain ends. Surface orientation of the FA ligand was optimized during PMNCF micelle preparation by controlling solvent solubility for FA. The out-oriented ligands on the micelles were immobilized by the strongly associated hydration layer around the closely packed phosphorylcholine zwitterions. The doxorubicin (DOX) loaded PMNCF micelles were demonstrated to reduce normal cell toxicity to less than 20%. More significantly, HeLa and MCF-7 tumor cell killing efficacy of the optimized formulation was enhanced to 160% compared with that of free DOX. The excellent performances of the drug loaded PMNCF micelles on both tumor cell killing and normal cell toxicity reducing efficacies reveal great potential for developing advanced drug delivery system.

Achieving superior anticoagulation of endothelial membrane mimetic coating by heparin grafting at zwitterionic biocompatible interfaces.

Thrombosis and bleeding are common complications of blood-contacting medical device therapies. In this work, an endothelium membrane mimetic coating (PMPCC/Hep) has been created to address these challenges. The coating is fabricated by multi-point anchoring of a phosphorylcholine copolymer (poly-MPC-co-MSA, PMPCC) with carboxylic side chains and end-group grafting of unfractionated heparin (Hep) onto polydopamine precoated blood-contacting material surfaces. The PMPCC coating forms an ultrathin cell outer membrane mimetic layer to resist protein adsorption and platelet adhesion. The tiny defects/pores of the PMPCC layer provide entrances for heparin end-group to be inserted and grafted onto the sub-layer amino groups. The combination of the PMPCC cell membrane mimetic anti-fouling nature with the grafted heparin bioactivity further enhances the anticoagulation performance of the formed endothelium membrane mimetic PMPCC/Hep coating. Compared to conventional Hep coating, the PMPCC/Hep coating further decreases protein adsorption and platelet adhesion by 50 % and 90 %, respectively. More significantly, the PMPCC/Hep coating shows a superior anticoagulation activity, even significantly higher than that of an end-point-attached heparin coating. Furthermore, the blood coagulation function is well preserved in the PMPCC/Hep coating anticoagulation strategy. All the results support that the PMPCC/Hep coating strategy has great potential in developing more efficient and safer blood-contacting medical devices.

Crosslinked biomimetic coating modified stainless-steel-mesh enables completely self-cleaning separation of crude oil/water mixtures.

The development of high-flux, durable and completely self-cleaning membranes is highly desired for separation of massive oil/water mixtures. Herein, differently crosslinked poly(2-methacryloyloxylethyl phosphorylcholine) (PMPC) brush grafted stainless steel mesh (SSM) membranes (SSM/PMPCs) were fabricated by integrating of mussel inspired universal adhesion and crosslinking chemistry with surface-initiated activators regenerated by electron transfer atom transfer radical polymerization (SI-ARGET-ATRP). The durability and self-cleaning performance of the prepared SSM membranes were evaluated by separating sticky crude oil/water mixtures in a continuous recycling dead-end filtration device. The water filtration flux driven by gravity reached 60,000 L⋅m-2⋅h-1 with a separation efficiency of over 99.98%. Furthermore, zero-flux-decline was observed during a 5 h continuous filtration when assisted by mechanical stirring. More significantly, such a completely self-cleaning separation of the well crosslinked SSM/PMPC2 membrane under optimized flux and stirring conditions had been operated cumulatively for 190 h in 30 days without any additional cleaning. These significant advances are more promising for practical applications in crude oil-contaminated water treatments and massive oil/water mixture separation.

Smart MSN-Drug-Delivery System for Tumor Cell Targeting and Tumor Microenvironment Release.

Tumor-targeted delivery and controlled release of antitumor drugs are promising strategies for increasing chemotherapeutic efficacy and reducing adverse effects. Although mesoporous silica nanoparticles (MSNs) have been known as a potential delivery system for doxorubicin (DOX), they have restricted applications due to their uncontrolled leakage and burst release from their large open pores. Herein, we engineered a smart drug-delivery system (smart MSN-drug) based on MSN-drug loading, cell membrane mimetic coating, on-demand pore blocking/opening, and tumor cell targeting strategies. The pore size of DOX-loaded MSNs was narrowed by polydopamine coating, and the pores/channels were blocked with tumor-targeting ligands anchored by tumor environment-rupturable -SS- chains. Furthermore, a cell membrane mimetic surface was constructed to enhance biocompatibility of the smart MSN-drug. Confocal microscopy results demonstrate highly selective uptake (12-fold in comparison with L929 cell) of the smart MSN-drug by HeLa cells and delivery into the HeLa cellular nuclei. Further in vitro IC50 studies showed that the toxicity of the smart MSN-drug to HeLa cells was 4000-fold higher than to the normal fibroblast cells. These exciting results demonstrate the utility of the smart MSN-drug capable of selectively killing tumor cells and saving the normal cells.

Universal Strategy for Efficient Fabrication of Blood Compatible Surfaces via Polydopamine-Assisted Surface-Initiated Activators Regenerated by Electron Transfer Atom-Transfer Radical Polymerization of Zwitterions.

Implant and blood-contacting biomaterials are challenged by biofouling and thrombus formation at their interface. Zwitterionic polymer brush coating can achieve excellent hemocompatibility, but the preparation often involves tedious, expensive, and complicated procedures that are designed for specific substrates. Here, we report a facile and universal strategy of creating zwitterionic polymer brushes on variety of materials by polydopamine (PDA)-assisted and surface-initiated activators regenerated by electron transfer atom-transfer radical polymerization (PDA-SI-ARGET-ATRP). A PDA adhesive layer is first dipcoated on a substrate, followed by covalent immobilization of 3-trimethoxysilyl propyl 2-bromo-2-methylpropionate (SiBr, ATRP initiator) on the PDA via condensation. Meanwhile, the trimethoxysilyl group of SiBr also cross-links the PDA oligomers forming stabilized PDA/SiBr complex coating. Finally, SI-ARGET-ATRP is performed in a zwitterionic monomer solution catalyzed by the parts per million level of CuBr2 without deoxygenization. The conveniently fabricated zwitterionic polymer brush coatings are demonstrated to have stable, ultralow fouling, and extremely blood compatible and functionalizable characteristics. This facile, versatile, and universal surface modification strategy is expected to be widely applicable in various advanced biomaterials and devices.

Anchorable phosphorylcholine copolymer synthesis and cell membrane mimetic antifouling coating fabrication for blood compatible applications.

Protein adsorption and platelet activation on biomedical devices contacting blood may lead to the formation of thrombus. The thrombogenicity of biomaterials could be minimized or prevented by anchoring a cell membrane mimetic antifouling coating (CMMAC). Here, we report the construction of a CMMAC by a newly designed 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymer (PMPCC) containing 5-20 carboxylic long arm side chains. The long arm provides its end carboxylic group with more freedom and a larger reaction space for an easier and more efficient surface anchoring. With the assistance of mussel-inspired universal adhesive polydopamine (PDA), different material surfaces precoated with PDA can immobilize the PMPCC via multipoint anchoring of the randomly distributed carboxylic side chains. The multipoint anchoring results in a stabilized and condensed PDA-PMPCC coating. The phosphorylcholine zwitterions of the densely immobilized PMPCC polymers form a cell outer membrane mimetic interface in an aqueous environment, endowing excellent properties of resisting protein adsorption, platelet activation and blood cell adhesion. More importantly, the PDA-PMPCC-coated glass surface can suppress thrombus formation for more than 24 h, while the bare glass surface forms obvious thrombus in 6 h tested in the same blood. Furthermore, the fabrication of the PDA-PMPCC coating is simple and material-independent. Therefore, the simple synthesis, facile surface coating and excellent hemocompatibility of the PMPCC make it a promising material for biomimetic surface modification.

A blood cell repelling and tumor cell capturing surface for high-purity enrichment of circulating tumor cells.

The detection of circulating tumor cells (CTCs), an approach considered to be "liquid biopsy", is crucial in cancer diagnosis, monitoring and prognosis. However, the extremely large number of blood cells challenges the rare CTC isolation and enrichment. In this report, a red blood cell membrane mimetic surface (CMMS) is fabricated on material-independent substrates to repel blood cell adhesion. Meanwhile, tumor cell targeting ligands, folic acid (FA) and an arginine-glycine-aspartic acid (RGD) peptide, are tethered on the CMMS to give the decorated surface (CMMS-FA-RGD) tumor cell capture ability. The CMMS is composed of a mussel-inspired self-adhesive polydopamine layer and a covalently anchored non-fouling or anti-cell-adhesion layer of a phosphorylcholine zwitterion polymer and poly(ethylene glycol) (PEG). The protruding ends of the PEG chains of the anchored CMMS are further coupled with FA and RGD ligands to endow the tumor cells with specific binding. Furthermore, all the components of the step-by-step constructed surfaces are quantitatively controllable for optimizing the non-specific cell repellence and tumor cell binding performances. Thus, the delicately engineered CTC capture surface enhances the HeLa cell enrichment factor to 19 000-fold by repelling the adhesion of >99.999% blood cells, resulting in high capture efficiency (91%) and capture purity (89%) from the spiked whole blood samples. This substrate independent tumor cell capture and blood cell repellent surface modification strategy may provide a facile, versatile and cost-effective technology solution for more efficient cancer diagnosis and targeted therapy.

Construction, mechanism, and antibacterial resistance insight into polypeptide-based nanoparticles.

The emergence of drug-resistant bacteria poses a serious threat to public health. The traditional antibiotics have specific intracellular targets and disinfect via chemical ways, which easily lead to the development of drug resistance, therefore, cationic peptides as promising antibiotic agents have attracted extensive attention due to their unique properties. Herein, we report a class of amphiphilic peptide-based pectinate polymers with primary amino groups. The polymers spontaneously self-assembled into the positively charged nanoparticles, which were evaluated and confirmed by scanning electron microscopy (SEM) and dynamic light scattering (DLS). Biological assays revealed that the nanoparticles showed broad-spectrum antibacterial efficacy against both Gram-positive and Gram-negative bacteria, exhibiting a MIC of 16 µg mL-1 against six clinical bacteria, namely, E. faecalis, S. aureus, MRSA, VRE, P. aeruginosa, and K. pneumonia, and three bacterial strains E. coli and E. coli producing NDM-1 and ImiS, and showed a sterilization rate of 95.6% and 94.7% on S. aureus and E. coli, respectively. Importantly, the nanoparticles did not result in drug-resistance for both the normal and drug-resistant bacteria tested after 14 passages and showed low toxicity on the mouse fibroblast cells (L929). The fluorescence staining, electrical conductivity, SEM, and surface plasmon resonance (SPR) characterization suggested that the nanoparticles initially bound to the surface of the bacteria, then pierced into the membranes of the bacteria with their phenyl groups, and finally disrupted the membranes, resulting in ions leaking out and thus exhibiting broad-spectrum antibacterial efficacy. This bactericidal mechanism that the nanoparticles employed does not lead the bacteria susceptible to developing drug resistance. This study provides a promising pathway for the development of the efficient antibacterial materials.

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

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 (∼1nm). 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∼3.3nm. Interestingly, both the PEG and PMEN thick coatings (≈3.6nm) 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 SIGNIFICANCE: Prevention 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.

Significantly reduced adsorption and activation of blood components in a membrane oxygenator system coated with crosslinkable zwitterionic copolymer.

UNLABELLED: A crosslinkable zwitterionic copolymer PMBT was coated onto the surfaces of polypropylene hollow fiber membrane (PP-HFM) oxygenator and its connecting tubes. The PMBT copolymer coating on the oxygenator circuit formed a cell outer membrane mimetic surface with excellent stability. The hemocompatibility of the PMBT copolymer coated PP-HFM oxygenator circuit was evaluated by animal extracorporeal circulation. The concentrations of clotting components fibrinogen and platelet in the blood were almost unchanged during the circulation through the PMBT copolymer coated oxygenator circuits. By contrast, the concentrations of fibrinogen and platelet were significantly reduced to 52% and 56% respectively in the uncoated oxygenator group due to adsorption and thrombogenesis of the blood during 2h circulation. Moreover, concentration of activation marker beta-thromboglobulin for platelet in the blood was remarkably lower in the PMBT group than the uncoated control group (p<0.01). All the results strongly supported that the hemocompatibility of the PP-HFM oxygenator circuit could be improved significantly by coating a stable and densely assembled zwitterionic polymer film. This simple, stable and highly effective cell membrane mimetic coating strategy may be applicable in developing advanced oxygenator systems and other artificial organs. STATEMENT OF SIGNIFICANCE: Although a number of studies have reported the fabrication of zwitterionic phosphorylcholine coated oxygenators to resist the adsorption and activation of blood components and eliminate heparin-induced thrombocytopenia, none of them have fabricated stable and densely assembled film, especially with crosslinkable amphiphilic random copolymer described in our manuscript. The novel features of our work include.

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

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.

Encapsulation of recombinant cells with a novel magnetized alginate for magnetic resonance imaging.

Implanting recombinant cells encapsulated in alginate microcapsules to express therapeutic proteins has been proven effective in treating several mouse models of human diseases (neurological disorders, dwarfism, hemophilia, lysosomal storage disease, and cancer). In anticipation of clinical application, we have reported the synthesis and characterization of a magnetized ferrofluid alginate that potentially allows tracking of these microcapsules in vivo by magnetic resonance imaging (MRI). We now report the properties of these ferrofluid microcapsules important for applications in gene therapy. When a mouse myoblast cell line was encapsulated in these microcapsules, it showed similar viability as in regular unmodified alginate capsules, both in vitro and in vivo, in mice. The permeability of these magnetized microcapsules, a critical parameter for immunoisolation devices, was comparable to that of classic alginate in the transit of various recombinant molecules of various molecular masses (human factor IX, 65 kDa; murine IgG, 150 kDa; and beta-glucuronidase, 300 kDa). When followed by MRI in vitro and in vivo, the ferrofluid microcapsules remained intact and visible for extended periods, allowing quantitative monitoring of microcapsules. At autopsy, the ferrofluid microcapsules were mostly free within the intraperitoneal cavities, with no overt inflammatory response. Serological analyses demonstrated a high level of biocompatibility comparable to that of unmodified alginate. In conclusion, ferrofluid-enhanced alginate microcapsules are comparable to classic alginate microcapsules in permeability and biocompatibility. Their visibility and stability to MRI monitoring permitted qualitative and quantitative tracking of the implanted microcapsules without invasive surgery. These properties are important advantages for the application of immunoisolation devices in human gene therapy.

Adhesion of human U937 macrophages to phosphorylcholine-coated surfaces.

A new type of amphiphilic phosphorylcholine (PC) polymer was used in this work to develop a cell culture surface that allows the attachment of U937 macrophages. The PC polymer was a random copolymer of N-isopropylacrylamide (45%), N-(phosphorylcholine)-N'-(ethylenedioxy-bis(ethyl)) acrylamide (41%), and the hydrophobic monomer N-(n-octadecyl) acrylamide (14%). Polypropylene (PP) films (1 cm2) were coated with the polymer solution by immersion. U937 macrophage suspensions were applied on PC polymer-coated surfaces and incubated for up to 72 h at 37 degrees C. While U937 cells did not adhere to PP, ammonia, nitrogen, or oxygen plasma-treated surfaces, they attached rapidly on PC-coated surfaces (< 1 h), proliferated, and stayed attached to the modified surface for at least 72 h, suggesting that unique features of the PC polymer, and the U937 macrophages, are responsible for the attachment of these cells. We compared the effect of Co2+ and Cr3+ ions on the expression of bone-resorbing cytokines (TNF-alpha, IL-6, IL-1beta) in U937 macrophages cultured on PC-coated surfaces to the response of U937 macrophages in suspension. Cytokine gene expression was analyzed by reverse transcription polymerase chain reaction (RT-PCR). Addition of Co2+ and Cr3+ ions led to a significant increased expression of TNF-alpha in both cultured and suspension cells. On the other hand, Co2+ and Cr3+ ions had a weak stimulatory effect or no effect on IL-1beta and IL-6, respectively, in both cultured and suspension cells. In conclusion, the use of PC polymer-modified surfaces might offer promising new opportunities for the culture of human U937 cells and may also point to the mechanism by which macrophages interact with lipid bilayers of biological membranes.

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

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.

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

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 90.5h. 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.

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

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.

Resonance energy transfer from dibucaine to acriflavine in polystyrene latex dispersions.

Resonance energy transfer from dibucaine (DC) to acriflavine (AF) has been investigated both in homogeneous aqueous solutions and in polystyrene latex dispersions. The energy transfer reaction is observed by monitoring fluorescence quenching of DC as well as sensitized emission of AF. It is found that the energy transfer from DC to AF is remarkably enhanced on going from the aqueous homogeneous solution to the latex dispersion. This is mainly attributed to the fact that both the donor and acceptor are effectively adsorbed onto the latex particles, as evidenced by the measurement of adsorption isotherms. From the adsorption experiments, it is also elucidated that electrostatic interaction is significant at low DC concentration, while hydrophobic interaction dominates at the higher concentration especially at higher pH.

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

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.

Preparation and characterization of zwitterionic phospholipid polymer-coated poly(lactic acid) nanoparticles.

Poly(lactic acid) (PLA) nanoparticles (NPs) are the most promising polymer NPs for drug delivery and targeting. However, they are easily recognized as a foreign body and rapidly cleared from the body by the mononuclear phagocyte system. Cell membrane mimetic random copolymers, bearing both zwitterionic phosphorylcholine groups and hydrophobic butyl side chains (PMB) and additional cross-linkable trimethoxysilylpropyl side chains (PMBT), were synthesized and coated on PLA NPs. Effects of the zwitterionic copolymer coatings on the NP size distribution, dispersion stability, and drug release behavior were investigated. Furthermore, the effect of the coatings on phagocytosis was also investigated. Compared with conventional polyvinyl alcohol coating, the cell membrane mimetic copolymer coatings decreased the size and increased the stability of the PLA NPs aqueous dispersions. More importantly, doxorubicin (DOX) release was well controlled and NPs phagocytosis by mouse peritoneal macrophage was decreased to one-third when the nanoparticles were coated with PMBT. This simple and effective zwitterionic polymer coating strategy may serve as a new route to design and optimize long-circulating intravenously injectable nanoparticle drug carriers.

CCDC26 gene polymorphism and glioblastoma risk in the Han Chinese population.

BACKGROUND: Glioblastoma (GBM) is an immunosuppressive tumor whose median survival time is only 12- 15 months, and patients with GBM have a uniformly poor prognosis. It is known that heredity contributes to formation of glioma, but there are few genetic studies concerning GBM. MATERIALS AND METHODS: We genotyped six tagging SNPs (tSNP) in Han Chinese GBM and control patients. We used Microsoft Excel and SPSS 16.0 statistical package for statistical analysis and SNP Stats to test for associations between certain tSNPs and risk of GBM in five different models. ORs and 95%CIs were calculated for unconditional logistic-regression analysis with adjustment for age and gender. The SHEsis software platform was applied for analysis of linkage disequilibrium, haplotype construction, and genetic associations at polymorphism loci. RESULTS: We found rs891835 in CCDC26 to be associated with GBM susceptibility at a level of p=0.009. The following genotypes of rs891835 were found to be associated with GBM risk in four different models of gene action: i) genotype GT (OR=2.26; 95%CI, 1.29-3.97; p=0.019) or GG (OR=1.33; 95%CI, 0.23-7.81; p=0.019) in the codominant model; ii) genotypes GT and GG (OR=2.18; 95%CI, 1.26-3.78; p=0.0061) in the dominant model; iii) GT (OR=2.24; 95%CI, 1.28-3.92; p=0.0053) in the overdominant model; iv) the allele G of rs891835 (OR=1.85; 95%CI, 1.14-3.00; p=0.015) in the additive model. In addition, "CG" and "CGGAG" were found by haplotype analysis to be associated with increased GBM risk. In contrast, genotype GG of CCDC26 rs6470745 was associated with decreased GBM risk (OR=0.34; 95%CI, 0.12-1.01; p=0.029) in the recessive model. CONCLUSIONS: Our results, combined with those from previous studies, suggest a potential genetic contribution of CCDC26 to GBM progression among Han Chinese.