W. T. Yang

Surface functionalization of polycaprolactone films via surface-initiated atom transfer radical polymerization for covalently coupling cell-adhesive biomolecules.

The ability to manipulate and control the surface properties, without altering the substrate properties, is of crucial importance in the designing of biomedical materials. In this work, surface-initiated atom transfer radical polymerization (ATRP) is employed to tailor the functionality of polycaprolactone (PCL) film surfaces in a well-controlled manner. Functional polymer brushes of glycidyl methacrylate (GMA) were prepared via surface-initiated ATRPs from the PCL film surfaces. Kinetics study revealed that the chain growth from the PCL films was consistent with a controlled process. The dense and reactive epoxide groups of the grafted P(GMA) brushes were used for the direct coupling of cell-adhesive collagen and Arg-Gly-Asp-Ser (RGDS) peptides to improve the cell-adhesion properties of the PCL film surface. These modified surfaces were evaluated by culturing of a cell line, 3T3 fibroblasts. The cell attachment and proliferation were improved remarkably on the collagen (or RGDS) functionalized PCL film surfaces. The adhesion results also indicated that the collagen-coupled PCL film surface is better for the cell-adhesion process. With the versatility of surface-initiated ATRP and the good biocompatibility nature of biomolecules, the PCL films with desirable surface functionalities can be precisely tailored to cater to various biomedical applications.

Improvement of hemocompatibility of polycaprolactone film surfaces with zwitterionic polymer brushes.

Polycaprolactone (PCL) has been widely adopted as a scaffold biomaterial, but further improvement of the hemocompatibility of a PCL film surface is still needed for wide biomedical applications. In this work, the PCL film surface was functionalized with zwitterionic poly(3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate) (P(DMAPS)) brushes via surface-initiated atom transfer radical polymerization (ATRP) for enhancing hemocompatibility. Kinetics study revealed an approximately linear increase in graft yield of the functional P(DMAPS) brushes with polymerization time. The blood compatibilities of the modified PCL film surfaces were studied by platelet adhesion tests of platelet-rich plasma and human whole blood, hemolysis assay, and plasma recalcification time (PRT) assay. The improvement of hemocompatibility is dependent on the coverage of the grafted P(DMAPS) brushes on the PCL film. Lower or no platelet and blood cell adhesion was observed on the P(DMAPS)-grafted film surfaces. The P(DMAPS) grafting can further decrease hemolysis and enhance the PRT of the PCL surface. With the versatility of surface-initiated ATRP and the excellent hemocompatibility of zwitterionic polymer brushes, PCL films with desirable blood properties can be readily tailored to cater to various biomedical applications.

Towards Highly Stable Storage of Sodium Ions: A Porous Na3V2(PO4)3/C Cathode Material for Sodium‐Ion Batteries

A porous Na3 V2 (PO4 )3 cathode material coated uniformly with a layer of approximately 6u2005nm carbon has been synthesized by the sol-gel method combined with a freeze-drying process. The special porous morphology and structure significantly increases the specific surface area of the material, which greatly enlarges the contact area between the electrode and electrolyte, and consequently supplies more active sites for sodium ions. When employed as a cathode material of sodium-ion batteries, this porous Na3 V2 (PO4 )3 /C exhibits excellent rate performance and cycling stability; for instance, it shows quite a flat potential plateau at 3.4u2005V in the potential window of 2.7-4.0u2005V versus Na(+) /Na and delivers an initial capacity as high as 118.9 and 98.0u2005mAu2009hu2009g(-1) at current rates of 0.05 and 0.5u2005C, respectively, and after 50u2005cycles, a good capacity retention of 92.7 and 93.6u2009% are maintained. Moreover, even when the discharge current density is increased to 5u2005C (590u2005mAu2009g(-1) ), an initial capacity of 97.6u2005mAu2009hu2009g(-1) can still be achieved, and an exciting capacity retention of 88.6u2009% is obtained after 100u2005cycles. The good cycle performance, excellent rate capability, and moreover, the low cost of Na3 V2 (PO4 )3 /C suggest that this material is a promising cathode for large-scale sodium-ion rechargeable batteries.

An integrated core–shell structured Li3V2(PO4)3@C cathode material of LIBs prepared by a momentary freeze-drying method

A homogeneous core–shell structured Li3V2(PO4)3@C cathode material of lithium-ion batteries was synthesized by a momentary freeze-drying method and exhibited good electrochemical properties, particularly its rate capability, for lithium ion storage.

Comb-Shaped Conjugates Comprising Hydroxypropyl Cellulose Backbones and Low-Molecular-Weight Poly(N-isopropylacryamide) Side Chains for Smart Hydrogels: Synthesis, Characterization, and Biomedical Applications

Hydroxypropyl cellulose (HPC) possesses a lower critical solution temperature (LCST) above 40 °C, while the poly(N-isopropylacrylamide) (P(NIPAAm)) exhibits a LCST of about 32 °C. Herein, comb-shaped copolymer conjugates of HPC backbones and low-molecular-weight P(NIPAAm) side chains (HPC-g-P(NIPAAm) or HPN) were prepared via atom transfer radical polymerization (ATRP) from the bromoisobutyryl-functionalized HPC biopolymers. By changing the composition ratio of HPC and P(NIPAAm), the LCSTs of HPNs can be adjusted to be lower than the body temperature. The MTT assay from the HEK293 cell line indicated that HPNs possess reduced cytotoxicity. Some of the hydroxyl groups of HPNs were used as cross-linking sites for the preparation of stable HPN hydrogels. In comparison with the HPC hydrogels, the cross-linked HPN hydrogels possess interconnected pore structures and higher swelling ratios. The in vitro release kinetics of fluorescein isothiocyanate-labeled dextran and BSA (or dextran-FITC and BSA-FITC) as model drugs from the hydrogels showed that the HPN hydrogels are suitable for long-term sustained release of macromolecular drugs at body temperature.

Functionalized layered double hydroxide nanoparticles conjugated with disulfide-linked polycation brushes for advanced gene delivery.

Layered double hydroxides (LDHs) have aroused great attention as potential nanosized drug delivery carriers, but independent inorganic LDH wrapped with DNA shows very low transfection efficiency. To manipulate and control the surface properties of LDH nanoparticles is of crucial importance in the designing of LDH-based drug carriers. In this work, surface-initiated atom transfer radical polymerization (ATRP) of 2-(dimethylamino)ethyl methacrylate (DMAEMA) is employed to tailor the functionality of LDH surfaces in a well-controlled manner and produce a series of well-defined novel gene delivery vectors (termed as LDH-PDs), where a flexible three-step method was first developed to introduce the ATRP initiation sites containing disulfide bonds onto LDH surfaces. In comparison the pristine LDH particles, the resultant LDH-PDs exhibited better ability to condense plasmid DNA (pDNA) and much higher levels to delivery genes in different cell lines including COS7 and HepG2 cell lines. Moreover, the LDH-PDs also could largely enhance cellular uptake. This present study demonstrates that functionalization of bioinorganic LDH with flexible polycation brushes is an effective means to produce new LDH-based gene delivery systems.

PCL Film Surfaces Conjugated with P(DMAEMA)/Gelatin Complexes for Improving Cell Immobilization and Gene Transfection

Successful gene transfection on a tissue scaffold is of crucial importance in facilitating tissue repair and regeneration by enabling the localized production of therapeutic drugs. Polycaprolactone (PCL) has been widely adopted as a scaffold biomaterial, but its unfavorable cell-adhesion property needs to be improved. In this work, the PCL film surface was conjugated with poly((2-dimethyl amino)ethyl methacrylate) (P(DMAEMA))/gelatin complexes via surface-initiated atom transfer radical polymerization (ATRP) for improving cell immobilization and subsequent gene transfection. A simple aminolysis-based method was first used for the covalent immobilization of ATRP initiators on the PCL film. Well-defined P(DMAEMA) brushes were subsequently prepared via surface-initiated ATRP from the initiator-functionalized PCL surfaces. The P(DMAEMA) chains with a pK(a) of 7.0-7.3 were used for conjugating gelatin with a pI of 4.7 via electrostatic interaction. The amount of complexed gelatin increased as that of the grafted P(DMAEMA) layer. The cell-adhesion property on the functionalized PCL surface could be controlled by adjusting the ratio of P(DMAEMA)/gelatin. It was found that the gene transfection property on the immobilized cells was dependent on the density of the immobilized cells on the functionalized PCL film. With the good cell-adhesive nature of gelatin and the efficient gene transfection on the dense immobilized cells, the incorporating the suitable of P(DMAEMA)/gelatin complexes onto PCL surfaces could endow the PCL substrates new and interesting properties for potential tissue engineering applications.

Thermoresponsive poly(N-isopropyl acrylamide)-grafted polycaprolactone films with surface immobilization of collagen.

Thermoresponsive poly(N-isopropylacrylamide) (P(NIPAAm))-grafted polycaprolactone (PCL) films with a suitable amount of immobilized cell-adhesive collagen were prepared to improve cell adhesion and proliferation above the lower critical solution temperature (LCST, 32°C) of P(NIPAAm) without destroying cell detachment properties at lower temperatures. Covalently tethered P(NIPAAm) brushes on PCL film surfaces were first prepared via surface-initiated atom transfer radical polymerization (ATRP). The alkyl bromide end groups of the grafted P(NIPAAm) brushes were used in nucleophilic substitution reactions for the direct coupling of collagen to produce the collagen-immobilized thermoresponsive PCL surface. At 37°C, the cell attachments on the collagen-immobilized thermoresponsive PCL surface were enhanced substantially. The attached cells could be recovered simply by lowering culture temperature. The P(NIPAAm)-grafted PCL films with immobilized collagen are potentially useful as adhesion modifiers for advanced cell culture and tissue engineering applications.

Preparation and evaluation of well-defined hemocompatible layered double hydroxide-poly(sulfobetaine) nanohybrids

The ability to manipulate and control the surface properties of layered double hydroxide (LDH) nanoparticles is of crucial importance in the designing of LDH-based carriers of therapeutic agents. In this work, surface-initiated atom transfer radical polymerization (ATRP) of zwitterionic 3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate (DMAPS) is first employed to tailor the functionality of LDH surfaces in a well-controlled manner and produce a series of well-defined hemocompatible hybrids (termed as LDHPS). The blood compatibilities of the modified LDH nanoparticles were investigated using coagulation tests, complement activation, platelet activation, hemolysis assay, morphological changes of red blood cells, and cytotoxicity assay. The results confirmed that the P(DMAPS) grafting can substantially enhance the hemocompatibility of the LDH particles, and the LDHPS hybrids can be used as biomaterials without causing any hemolysis. With the versatility of surface-initiated ATRP and the excellent hemocompatibility of zwitterionic polymer chains, the LDH nanoparticles with desirable blood properties can be readily tailored to cater to various biomedical applications.

An oligopeptide ligand-mediated therapeutic gene nanocomplex for liver cancer-targeted therapy

The epidermal growth factor receptor (EGFR) is over-expressed in a wide variety of epithelial-derived cancer cells. In this study, EGFR-targeted gene carriers were designed to complex the therapeutic acetylcholinesterase gene (AChE gene), which suppresses cell proliferation via inactivating mitogen-activated protein kinase and PI3K/Akt pathways in cells, for treatment of EGFR-positive liver cancers. Different amounts of target ligand YC21 (an oligopeptide composed of 21 amino acid units) were coupled with the PEI(600)-CD (PC) vectors composed of β-cyclodextrin (β-CD) and low-molecular-weight polyethylenimine (PEI, Mw 600) to form the EGFR-targeted gene vectors (termed as YPCs). The YPC vectors possessed the highly efficient gene delivery ability to the EGFR-positive liver cancer cells. YPCs could effectively promote AChE gene expression. The YPC/AChE complexes produced excellent gene transfection abilities in EGFR-positive liver cancer cells in vitro and in vivo.