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Enhanced gene transfection and serum stability of polyplexes by PDMAEMA-polysulfobetaine diblock copolymers

Paper ID Volume ID Publish Year Pages File Format Full-Text
8299 584 2011 11 PDF Available
Title
Enhanced gene transfection and serum stability of polyplexes by PDMAEMA-polysulfobetaine diblock copolymers
Abstract

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.

Keywords
2-(dimethylamino) ethyl methacrylate; Sulfobetaine; Gene delivery; Serum stability
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Enhanced gene transfection and serum stability of polyplexes by PDMAEMA-polysulfobetaine diblock copolymers
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 2, January 2011, Pages 628–638
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us