Journal
NANOMEDICINE
Volume 11, Issue 3, Pages 235-247Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/nnm.15.193
Keywords
anti-miR; cancer therapy; orlistat; PLGA nanoparticles; TNBC
Funding
- NIH [R01 CA161091]
- NATIONAL CANCER INSTITUTE [R01CA161091] Funding Source: NIH RePORTER
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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.
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