Orlistat and antisense-miRNA-loaded PLGA-PEG nanoparticles for enhanced triple negative breast cancer therapy

被引:59
作者
Bhargava-Shah, Aarohi [1 ]
Foygel, Kira [1 ]
Devulapally, Rammohan [1 ]
Paulmurugan, Ramasamy [1 ]
机构
[1] Stanford Univ, Sch Med, Bio X Program, Mol Imaging Program Stanford, Palo Alto, CA 94304 USA
关键词
anti-miR; cancer therapy; orlistat; PLGA nanoparticles; TNBC; FATTY-ACID SYNTHASE; POLYMER NANOPARTICLES; DRUG-DELIVERY; EXPRESSION; PROGRESSION; CARCINOMA; CELLS;
D O I
10.2217/nnm.15.193
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 [微生物学]; 090105 [作物生产系统与生态工程];
摘要
Background: This study explores the use of hydrophilic poly(ethylene glycol)conjugated poly(lactic-co-glycolic acid) nanoparticles (PLGA-PEG-NPs) as delivery system to improve the antitumor effect of antiobesity drug orlistat for triple-negative breast cancer (TNBC) therapy by improving its bioavailability. Materials & methods: PLGA-PEG-NPs were synthesized by emulsion-diffusion-evaporation method, and the experiments were conducted in vitro in MDA-MB-231 and SKBr3 TNBC and normal breast fibroblast cells. Results: Delivery of orlistat via PLGA-PEG-NPs reduced its IC50 compared with free orlistat. Combined treatment of orlistat-loaded NPs and doxorubicin or antisense-miR-21-loaded NPs significantly enhanced apoptotic effect compared with independent doxorubicin, anti-miR-21-loaded NPs, orlistat-loaded NPs or free orlistat treatments. Conclusion: We demonstrate that orlistat in combination with antisense-miR-21 or current chemotherapy holds great promise as a novel and versatile treatment agent for TNBC.
引用
收藏
页码:235 / 247
页数:13
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