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

Jun Zhang, Jia Song, Xiao Liang, Yunzhi Yin, Tiantian Zuo, Daijie Chen, Qi Shen

Nanomedicine 2019 January 30

AIM: Enzyme CYP1B1 (CYP1B1) is usually overexpressed in multidrug resistance (MDR) breast cancer cells, which could metabolically inactivate docetaxel (DTX).

MATERIALS & METHODS: 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.

RESULTS: 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.

CONCLUSION: The HA/PEI NPs might be a promising strategy to overcome CYP1B1-mediated breast cancer MDR.

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