کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8299 584 2011 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Enhanced gene transfection and serum stability of polyplexes by PDMAEMA-polysulfobetaine diblock copolymers
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
Enhanced gene transfection and serum stability of polyplexes by PDMAEMA-polysulfobetaine diblock copolymers
چکیده انگلیسی

Polyethylene glycol or phosphorylcholine is often introduced into polycationic non-viral vectors to inhibit the non-specific protein adsorption. However the ability of vectors to condense DNA and the cellular internalization of complexes are unavoidably compromised. In this work, a polysulfobetaine-cationic methacrylate copolymer: 2-(dimethylamino) ethyl methacrylate-block-(N-(3-(methacryloylamino) propyl)-N,N-dimethyl-N-(3-sulfopropyl) ammonium hydroxide) (PDMAEMA-b-PMPDSAH) diblock copolymer was synthesized via atomic transfer radical polymerization method and investigated as a new non-viral vector for gene delivery. Incorporation of polysulfobetaine into cationic methacrylate retained a better DNA condensation capability. MTT assays revealed that the cytotoxicity of PDMAEMA200-PMPDSAHn copolymer was lower than that of PDMAEMA200. PDMAEMA200-PMPDSAH80 which was much superior to its homopolymer in mediating gene transfection demonstrated comparable efficiency to PEI25 kDa at a weight ratio of 8 in the presence of 10% serum. At higher serum contents, the transfection of PDMAEMA200 and PEI25 kDa was deteriorated, whereas PDMAEMA200-PMPDSAH80 still retained better transfection efficiency, 4–5 fold more effective than PEI25 kDa. For the sake of comparative study, we synthesized structurally similar copolymer from DMAEMA and 2-methacryloyloxyethyl phosphorylcholine, PDMAEMA200-PMPC80. PDMAEMA200-PMPDSAH80 exhibited much higher gene transfer levels than PDMAEMA200-PMPC80 under the same conditions. The results of flow cytometry indicated that highly hydrophilic MPC block profoundly impeded the cellular internalization of nanocomplexes; in contrast, incorporation of polysulfobetaine remained the increased cellular uptake. Differential scanning calorimetry assay of thermodynamic phase transition of dipalmitoyl-sn-glycero-3-phosphocholine(DPPC) induced by polymer vectors demonstrated that MPC only marginally contributed to the perturbation of DPPC; polysulfobetaine facilitated more evident perturbation of DPPC bilayer instead, an indication that polysulfobetaine units could aid in the endocytosis of nanocomplexes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 32, Issue 2, January 2011, Pages 628–638
نویسندگان
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