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Nonviral Gene Carriers Based on Diblock Copolymers of Poly(2-ethyl-2-oxazoline) and Linear Polyethylenimine
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文摘
Diblock copolymers that consist of poly(2-ethyl-2-oxazoline) (PEOz) and linear polyethylenimine (LPEI) wereprepared for use as nonviral gene carriers. The PEOz-b-LPEI copolymers were synthesized by coupling PEOzwith LPEI in a thiol-disulfide exchange reaction between the sulfhydryl and pyridyl disulfide terminal groups.A polymer/DNA weight ratio (P/D) of over 12 was required to enable PEOz-b-LPEI to condense DNA completely.The DNA-condensing capability of the diblock copolymers was increased with increasing the hydrolytic degrees of the LPEI segment. The PEOz-b-LPEI polyplexes were stable in 150 mM NaCl aqueous solution andhad a mean diameter around 190 nm, whereas BPEI and LPEI polyplexes formed large aggregates in the range300-500 nm. In addition, these polyplexes exhibited the sensitivity to solution pH and were dissociated in theacidic buffers (pH 5.5). The results of in vitro cell viability and luciferase assay indicated that PEOz-b-LPEIshowed not only low cytotoxicity but also high transfection efficiency in gene expression.

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