期刊
ACS MEDICINAL CHEMISTRY LETTERS
卷 4, 期 8, 页码 720-723出版社
AMER CHEMICAL SOC
DOI: 10.1021/ml4001003
关键词
Nanoparticle; siRNA delivery; iNOP; reducible nanoparticles
资金
- NIH
RNA interference (RNAi) has considerable potential as a therapeutic strategy, but the development of efficient in vivo RNA delivery methods remains challenging. To this end, we designed and synthesized chemically modified interfering nanoparticles (iNOPs) composed of functionalized poly-L-lysine dendrimers modified with reducible spacers to facilitate release of small interfering RNAs (siRNAs) in vivo. We show that the novel siRNA-iNOP complexes mediate efficient gene-specific RNAi in cultured cells and in mice, where they display enhanced tissue-targeting capabilities. At a clinically feasible dose of 1 mg kg(-1), apolipoprotein B (apoB) siRNA-iNOP complexes achieved similar to 40-45% reduction of liver apoB mRNA and plasma apoB protein levels within 48 h of administration to mice, without apparent toxicity. Collectively, these findings demonstrate that siRNA delivery by the modified reducible iNOPs can provide a clinically significant and potentially tissue-specific new approach for RNAi therapy.
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