期刊
ACS NANO
卷 6, 期 8, 页码 7340-7351出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn3024688
关键词
siRNA; layer-by-layer assembly; charge-reversible
类别
资金
- China Postdoctoral Science Foundation [Y1321Z11GJ]
- Chinese Natural Science Foundation [30970784, 81171455]
- National Key Basic Research Program of China [2009CB930200]
- Chinese Academy of Sciences (CAS) [07165111ZX]
- Research Fund for the Doctoral Program of Higher Education of China [20111301110004]
A simple nano-carrier coated with chitosan and the pH-responsive charge-reversible polymer, PAH-Cit, was constructed using layer-by-layer assembly to deliver siRNA. Gold nanoparticles (AuNPs) were directly reduced and stabilized by chitosan (G), forming a positively charged AuNP-CS core. Charge-reversible PAH-Cit and polyethylenimine (PEI) were sequentially deposited onto the surface of AuNP-CS through electrostatic interaction, forming a PEI/PAH-Cit/AuNP-CS shell/core structure. After loading siRNA, the cytotoxicity of siRNA/PEI/PAH-Cit/AuNP-CS against Hela and MCF-7R cells was negligible. This vehicle completely protected siRNA against enzymatic degradation at vector/RNA mass ratios of 2.5:1 and above. An in vitro release profile demonstrated an efficient siRNA release (79%) from siRNA/PEI/PAH-Cit/AuNP-CS at pH 5.5, suggesting a pH-induced charge-reversing action of PAH-Cit. This mechanism also worked in vivo and facilitated the escape of siRNA from endosomes. Using this carrier, the uptake of cy5-siRNA by Hela cells was significantly increased compared to PEI, an efficient polycationic transfection reagent In drug-resistant MCF-7 cells, specific gene silencing effectively reduced expression of MDR1, the gene encoding the drug exporter Pip, and consequently promoted the uptake of doxorubicin. This simple charge-reversal polymer assembly nanosystem has three essential benefits (protection, efficient uptake, and facilitated escape) and provides a safe strategy with good biocompatibility for enhanced siRNA delivery and silencing.
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