期刊
ACS MACRO LETTERS
卷 2, 期 8, 页码 725-730出版社
AMER CHEMICAL SOC
DOI: 10.1021/mz400331w
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资金
- NIH/NINDS [1R01NS064404]
- NSF DMR [1206426]
- NSF [DGE-0718124]
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [1206426] Funding Source: National Science Foundation
Endosomal release peptides have been incorporated in synthetic gene delivery formulations to increase transfection efficiencies. In this work, cationic copolymers containing sHGP, a membrane-lytic peptide derived from HIV gp41, were synthesized and evaluated. Diblock, with sHGP displayed on one block, and statistical, with sHGP randomly displayed, copolymers were prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization. While the statistical copolymers existed as unimers in solution, amphiphilic diblock copolymers self-assembled into cationic micelles in aqueous solution as evidenced by transmission electron microscopy (TEM) and dynamic light scattering analyses. This self-assembly sequestered the lytic domain and significantly reduced the cytotoxicity of the materials. However, when complexed with plasmid DNA, both the diblock and statistical copolymers of sHGP showed higher gene delivery efficacy compared to the copolymers without the membrane lytic motif. The ability of amphiphilic, diblock copolymers containing endosomal release motifs to self-assemble and sequester lytic domains is a promising feature for the nucleic acid delivery.
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