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