期刊
JOURNAL OF MATERIALS CHEMISTRY B
卷 3, 期 19, 页码 4027-4035出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4tb01956c
关键词
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资金
- National Natural Science Foundation of China [31371014, 31100722, 51203111]
- Tianjin Natural Science Foundation [13JCYBJC16500]
- Chinese Natural Science Foundation Project [30970784, 81171455]
- National Distinguished Young Scholars grant from the National Natural Science Foundation of China [31225009]
- National Key Basic Research Program of China [2009CB930200]
- Chinese Academy of Sciences (CAS) Hundred Talents Program'' [07165111ZX]
- CAS Knowledge Innovation Program
- State High-Tech Development Plan [2012AA020804]
- Strategic Priority Research Program'' of the Chinese Academy of Sciences [XDA09030301]
Cationic polymers (polycations) are promising gene vectors that are conveniently synthesized and easily modified. In order to study the relationship between structures and properties of the polycations in gene delivery, a graft copolymer called poly(N-vinylpyrrolidone)-g-poly(2-dimethylaminoethyl methacrylate) (PVP-g-PDMAEMA, i.e. PgP) and a block copolymer called PVP-b-PDMAEMA (PbP) with equal molecular weight of PDMAEMA and PVP were prepared by two advanced living radical polymerization reactions including atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain transfer (RAFT) techniques. Compared with PbP, PgP could condense pDNA more effectively into polyplexes with smaller size, higher zeta potential and better stability. The transfection efficiency of PgP at a low N/P ratio of 4 : 1 was not only higher than that of PbP, but also much higher than that of the commercially available PEI as the gold standard of polycations and lipofectamine. In addition, both PgP and PbP had less BSA absorption compared with PEI, indicating that PVP could resist BSA absorption. In order to understand the mechanism behind the high transfection efficiency of PgP, cellular uptake and endosomal escape of PgP/pDNA and PbP/pDNA polyplexes were investigated. The results demonstrated that the improvement of the transfection efficiency of PgP originated from the promotion of the cellular uptake and endosome/lysosome escape. This study will provide useful information on designing effective non-viral vectors for gene delivery.
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