Targeted delivery of miRNA-204-5p by PEGylated polymer nanoparticles for colon cancer therapy

被引:43
作者
Zheng, Bo [1 ,2 ]
Chen, Lu [1 ,2 ]
Pan, Chun-Chun [1 ,2 ]
Wang, Jian-Zhang [1 ,2 ]
Lu, Guang-Rong [1 ,2 ]
Yang, Shou-Xing [1 ,2 ]
Xue, Zhan-Xiong [1 ,2 ]
Wang, Fang-Yan [3 ]
Xu, Chang-Long [1 ,2 ,4 ]
机构
[1] Wenzhou Med Univ, Affiliated Hosp 2, Dept Gastroenterol, Wenzhou 325000, Zhejiang, Peoples R China
[2] Wenzhou Med Univ, Childrens Hosp, Wenzhou 325000, Zhejiang, Peoples R China
[3] Wenzhou Med Univ, Sch Basic Med Sci, Dept Pathophysiol, Wenzhou 325000, Zhejiang, Peoples R China
[4] Georgia State Univ, Inst Biomed Sci, Ctr Diagnost & Therapeut, Atlanta, GA 30302 USA
关键词
colon cancer therapy; miRNA; polymer nanoparticle; targeted delivery; COLORECTAL-CANCER; DRUG-DELIVERY; MICRORNA THERAPEUTICS; CO-DELIVERY; GENE; CELLS; CHEMOTHERAPY; PERSPECTIVE; DOXORUBICIN; LIPOPLEXES;
D O I
10.2217/nnm-2017-0345
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Aim: miRNAs have been recognized for their potential in cancer therapeutics, and multiple miRNAs were suggested to affect target genes expression. To overcome limitations of free synthetic miRNAs, such as easily degraded in biofluids and limited in cellular uptake, novel miRNAs delivery systems need to be developed. Materials & methods: Using surface-functionalizing technique, poly(D,L-lactide-co-glycolide)/poly(L-lactide)-block-poly(ethylene glycol)-folate polymer nanoparticle (PLGA/PLA-PEG-FA) loaded with miR-204-5p (FA-NPs-miR-204) was developed. The therapeutic efficacy of FA-NPs-miR-204 was evaluated in the Luc-HT-29 xenograft tumor model in vivo. Results: FA-NPs-miR-204 could be taken up by HT-29 and HCT-116 cells efficiently, resulting in significant inhibitory effect on cell proliferation and promotive effect on cell apoptosis. In vivo study showed that FA-NPs-miR-204 could exert tumor suppressive function in Luc-HT-29 xenograft model. Conclusion: Our study demonstrates a convenient miRNA delivery system that targets tumor tissue and exerts tumor suppressive function, thus demonstrating a potential new therapeutic option for colon cancer.
引用
收藏
页码:769 / 785
页数:17
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