HPMA-oligolysine copolymers for gene delivery: optimization of peptide length and polymer molecular weight.

HPMA-oligolysine copolymers for gene delivery: optimization of peptide length and polymer molecular weight.
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DOI:
10.1016/j.jconrel.2011.07.009
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发表时间:
2011-10-30
期刊:
Journal of controlled release : official journal of the Controlled Release Society
影响因子:
--
通讯作者:
Pun SH
Pun SH
中科院分区:
其他
文献类型:
--
作者:
Johnson RN;Chu DS;Shi J;Schellinger JG;Carlson PM;Pun SH

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Polycations are one of the most frequently used classes of materials for non-viral gene transfer in vivo. Several studies have demonstrated a sensitive relationship between polymer structure and delivery activity. In this work, we used reverse addition-fragmentation chain transfer (RAFT) polymerization to build a panel of N-(2-hydroxypropyl(methacrylamide) (HPMA)-oligolysine copolymers with varying peptide length and polymer molecular weight. The panel was screened for optimal DNA-binding, colloidal stability in salt, high transfection efficiency, and low cytotoxicity. Increasing polyplex stability in PBS correlated with increasing polymer molecular weight and decreasing peptide length. Copolymers containing K5 and K10 oligocations transfected cultured cells with significantly higher efficiencies than copolymers of K15. Four HPMA-oligolysine copolymers were identified that met desired criteria. Polyplexes formed with these copolymers demonstrated both salt stability and transfection efficiencies on-par with poly(ethylenimine) PEI in cultured cells.
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