Biomimetic Polymer Brushes Containing Tethered Acetylcholine Analogs for Protein and Hippocampal Neuronal Cell Patterning
ABSTRACT This paper describes a method to control neuronal cell adhesion and differentiation with both chemical and topographic cues by using a spatially defined polymer brush pattern. First, biomimetic methacrylate polymer brushes containing tethered neurotransmitter acetylcholine functionalities in the form of dimethylaminoethyl methacrylate (DMAEMA), or free hydroxyl-terminated poly(ethylene glycol) (PEG) units were prepared using the "grown from" method through surface-initiated atom transfer radical polymerization (SI-ATRP) reactions. The surface properties of the resulting brushes were thoroughly characterized with various techniques and hippocampal neuronal cell culture on the brush surfaces exhibit cell viability and differentiation comparable to, or even better than, those on commonly used poly-L-lysine coated glass coverslips. The polymer brushes were then patterned via UV photolithography techniques to provide specially designed surface features with different sizes (varying from 2 µm to 200 µm) and orientations (horizontal and vertical). Protein absorption experiments and hippocampal neuronal cell culture tests on the brush patterns showed that both protein and neurons can adhere to the patterns and therefore be guided by such patterns. These results also demonstrate that, because of their unique chemical composition and well-defined nature, the developed polymer brushes may find many potential applications in cell-material interactions studies and neural tissue engineering.
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ABSTRACT: An emerging strategy for synergistic gene and drug therapy is establishing a new paradigm for the synthesis of diversified and functional block copolymers with applications ranging from gene and drug delivery to fluorescence detection. In this paper, we report on a novel amphiphilic block copolymer containing a fluorescent coumarin derivative (CE), an acid-cleavable (acetal group, -a-) linkage between hydrophobic poly(3-caprolactone) (PCL) and hydrophilic poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) and poly[poly(ethylene glycol)methyl ether methacrylate] (PPEGMA) blocks, abbreviated as CE-PCL-a-(PDMAEMA-co-PPEGMA), which was synthesized by a combination of atom transfer radical polymerization (ATRP), ring-opening polymerization (ROP) and CuAAC “click” reaction. The chemical composition and structures of these copolymers were fully characterized by 1H NMR and FT-IR analyses, while the molecular weights and molecular weight distributions were measured by gel permeation chromatography (GPC). The micelles self-assembled from these block copolymers could simultaneously encapsulate anti-cancer drug doxorubicin (DOX) and DNA to form a micelleplex with the hydrophilic brush-type PPEGMA on the surface, and the loaded cargoes could be released after the acetal linkage was cleaved under intracellular acidic conditions. Subsequently, the formed micelles as the drug and gene co-delivery vectors were investigated by employing gel retardation assay, zeta potential, dynamic light scattering (DLS), and transmission electron microscopy (TEM). A fluorescence spectrometer was further used to evaluate the fluorescence of polymers. Finally, in vitro drug release, cytotoxicity and transfection were also studied. All these results indicated that this acidcleavable and fluorescent block copolymer would hold significant potential as a combined drug and DNA carrier.04/2014; 2(27):4237. DOI:10.1039/c4tb00334a
Chemical Reviews 10/2014; 114(21). DOI:10.1021/cr500252u · 45.66 Impact Factor
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ABSTRACT: Bovine serum albumin (BSA) modified polypropylene (PP) was fabricated via surface-initiated atom transfer radical polymerization (SI-ATRP) of poly(ethylene glycol) methacrylate (PEGMA) and glycidyl methacrylate (GMA). Kinetics study revealed an approximately linear increase in graft density of the functional brushes with polymerization time. Attenuated total reflectance Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy confirmed that comonomers and BSA were successfully immobilized onto PP film. The hydrophilicity of PP was improved by modification with PEGMA and GMA. The balance between the inhibition of BSA adsorption by PEGMA and the covalent immobilization of BSA by GMA through the ring-opening reaction of the epoxy group resulted in the moderate fluorescence intensity of FITC-BSA immobilized PP-g-P (PEGMA-co-GMA). The hemolysis test showed that BSA could decrease the hemolysis rate. Red blood cell membrane maximal stress can be reduced by the inertness of BSA as well as the repulsion caused by its electrostatic interactions. Whole blood cell attachment tests showed that BSA molecules weakened the interaction between blood cells and the PP surface. Therefore, the immobilization of BSA on PP film is an effective approach for improving the hemocompatibility of PP.RSC Advances 01/2014; 4(47-47):24842-24851. DOI:10.1039/c4ra03652b · 3.71 Impact Factor