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

Nanomedicine
Aarohi Bhargava-ShahRamasamy Paulmurugan

Abstract

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. 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. 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. 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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Citations

Sep 15, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Seong Lin Teoh, Srijit Das
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Dec 15, 2016·ACS Applied Materials & Interfaces·Rammohan DevulapallyRamasamy Paulmurugan

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Methods Mentioned

BETA
nanoprecipitation
antisense oligonucleotides
dynamic light scattering
FACS
xenograft

Software Mentioned

FlowJo

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