(512i) Co-Delivery of miRNA Inhibitor and Doxorubicin for Enhanced Anticancer Therapy

Co-delivery of miRNA inhibitor and doxorubicin for enhanced anticancer therapy

 Zilan Zhou, Apurva Badkas, and Joo-Youp Lee

Chemical Engineering Program

Department of Biomedical, Chemical, and Environmental Engineering

University of Cincinnati, Cincinnati, Ohio 45221-0012

The development of nano-scaled carriers as a drug delivery platform has made a tremendous difference in the fight against cancer.  Among these nano-scaled carriers, various nanoparticles (NPs) made of biocompatible and biodegradable materials have been of particular interest.  Significant progresses have been made in improving NP formulations, targeting, and drug potency.  Despite the progresses, drug resistance remains a major challenge that NP-based cancer therapeutics still faces.  RNA interference (RNAi) using miRNA inhibitor, a small non-coding RNA molecule, has been considered as a promising strategy to tackle the drug resistance.  Recently, our group developed a novel nanoparticle system using biocompatible polymer PLGA-PHis-PEG for the co-delivery of miRNA inhibitor 221/222 and doxorubicin.  In our approach, the miRNA inhibitors with negative charges were condensed with calcium phosphate (CaP) with positive charges to form solid particles via electrostatic interactions.  Then an excess amount of positive charges were neutralized by coating the solid particles with anionic lipids.  As a result, the entire lipid/CaP/miRNA complex (LCPR) could be encapsulated inside the polymeric nanoparticle with a chemotherapic drug, doxorubicin, via nanoprecipitation.    In this talk, the efficacy of the co-delivery system will be reported.