Hyaluronic acid-modified cationic nanoparticles overcome enzyme CYP1B1-mediated breast cancer multidrug resistance.

Abstract

Enzyme CYP1B1 (CYP1B1) is usually overexpressed in multidrug resistance (MDR) breast cancer cells, which could metabolically inactivate docetaxel (DTX). The cationic core-shell nanoparticles (hyaluronic acid/polyethyleneimine nanoparticles[HA/PEI NPs]) modified with hyaluronic acid (HA) were developed and coloaded with DTX and α-napthtoflavone (ANF, a CYP1B1 inhibitor) to overcome MDR in breast cancer induced by CYP1B1. Physicochemical characterization, MDR reversing effect in vitro and pharmacokinetics in vivo of HA/PEI NPs were evaluated. The HA/PEI NPs exhibited spherical morphology with size of (193.6±3.1) nm. The HA/PEI NPs could reverse MDR effectively by downregulating the expression of CYP1B1. The HA/PEI NPs improved the bioavailability of DTX. The HA/PEI NPs might be a promising strategy to overcome CYP1B1-mediated breast cancer MDR.