Systemic delivery of siRNA with cationic lipid assisted PEG-PLA nanoparticles for cancer therapy

被引:223
作者
Yang, Xian-Zhu [2 ]
Dou, Shuang [1 ,3 ]
Sun, Tian-Meng [2 ]
Mao, Cheng-Qiong [1 ,3 ]
Wang, Hong-Xia [1 ,3 ]
Wang, Jun [1 ,3 ]
机构
[1] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China
[2] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China
[3] Univ Sci & Technol China, CAS Key Lab Brain Funct & Dis, Hefei 230027, Anhui, Peoples R China
基金
中国国家自然科学基金;
关键词
siRNA delivery; Nanoparticle; RNA interference; Cancer therapy; Polo-like kinase 1; BIODEGRADABLE POLYMER; PLGA NANOPARTICLES; RNAI; THERAPEUTICS; TUMOR; MICROPARTICLES; MICROSPHERES; MODULATION; COPOLYMER; HYDROGELS;
D O I
10.1016/j.jconrel.2011.07.035
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Delivery of small interfering RNA (siRNA) has been one of the major hurdles for the application of RNA interference in therapeutics. Here, we describe a cationic lipid assisted polymeric nanoparticle system with stealthy property for efficient siRNA encapsulation and delivery, which was fabricated with poly(ethylene glycol)-b-poly(d,l-lactide), siRNA and a cationic lipid, using a double emulsion-solvent evaporation technique. By incorporation of the cationic lipid, the encapsulation efficiency of siRNA into the nanoparticles could be above 90% and the siRNA loading weight ratio was up to 4.47%, while the diameter of the nanoparticles was around 170 to 200 nm. The siRNA retained its integrity within the nanoparticles, which were effectively internalized by cancer cells and escaped from the endosome, resulting in significant gene knockdown. This effect was demonstrated by significant down-regulation of luciferase expression in HepG2-luciferase cells which stably express luciferase, and suppression of polo-like kinase 1 (Plk1) expression in HepG2 cells, following delivery of specific siRNAs by the nanoparticles. Furthermore, the nanoparticles carrying siRNA targeting the Plk1 gene were found to induce remarkable apoptosis in both HepG2 and MDA-MB-435s cancer cells. Systemic delivery of specific siRNA by nanoparticles significantly inhibited luciferase expression in an orthotopic murine liver cancer model and suppressed tumor growth in a MDA-MB-435s murine xenograft model, suggesting its therapeutic promise in disease treatment. (C) 2011 Elsevier B. V. All rights reserved.
引用
收藏
页码:203 / 211
页数:9
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