期刊
ADVANCED HEALTHCARE MATERIALS
卷 3, 期 11, 页码 1792-1803出版社
WILEY
DOI: 10.1002/adhm.201400037
关键词
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资金
- National Basic Research Program of China (973 Programs) [2010CB934001]
- National High Technology Research and Development Program of China (863 Program) [2014AA020708]
- National Natural Science Foundation of China [51203145, 51390482, 81172526, 81302724]
- Anhui Provincial Natural Science Foundation [1308085QB26]
- Fundamental Research Funds for the Central Universities [2014HGCH0014, 2013HGCH0001]
- China Postdoctoral Science Foundation [2012M511407, 2013T60614, 2012M521258]
Patients with Her2-overexpressing (Her2(+)) breast cancers generally have a poorer prognosis due to the high aggressiveness and chemoresistance of the disease. Small interfering RNA (siRNA) targeting the gene encoding polo-like kinase 1 (Plk1; si Plk1) has emerged as an efficient therapeutic agent for Her2(+) breast cancers. Poly(ethylene glycol)-block-poly(D,L-lactide) (PEG-PLA)-based nanoparticles for siRNA delivery were previously developed and optimized. In this study, for targeted delivery of si Plk1 to Her2(+) breast cancer, anti-Her2 single-chain variable fragment antibody (ScFv(Her2))-decorated PEG-PLA-based nanoparticles with si Plk1 encapsulation (ScFv(Her2)-NP(si)Plk1) are developed. With the rationally designed conjugation site, ScFv(Her2)-NP(si)RNA can specifically bind to the Her2 antigen overexpressed on the surface of Her2(+) breast cancer cells. Therefore, ScFv(Her2)-NP(si)Plk1 exhibits improved cellular uptake, promoted Plk1 silencing efficiency, and induced enhanced tumor cell apoptosis in Her2(+) breast cancer cells, when compared with nontargeted NP(si)Plk1. More importantly, ScFv(Her2)-NPsiRNA markedly enhances the accumulation of siRNA in Her2(+) breast tumor tissue, and remarkably improves the efficacy of tumor suppression. Dose-dependent anti-tumor efficacy further demonstrates that ScFv(Her2)-decorated PEG-PLA-based nanoparticles with si Plk1 encapsulation can significantly enhance the inhibition of Her2(+) breast tumor growth and reduce the dose of injected siRNA. These results suggest that ScFv(Her2)-decorated PEG-PLA-based nanoparticles show great potential for targeted RNA interference therapy of Her2(+) breast tumor.
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