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Nanomedicine (Lond). 2019 Feb;14(4):447-464. doi: 10.2217/nnm-2018-0244. Epub 2019 Jan 29.

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

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1
School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.

Abstract

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.

KEYWORDS:

CD44; CYP1B1; DTX; breast cancer; hyaluronic acid; lysosome escape; multidrug resistance; nanoparticles; polyethyleneimine; α-napthtoflavone

PMID:
30694105
DOI:
10.2217/nnm-2018-0244
[Indexed for MEDLINE]

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