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

被引:18
作者
Zhang, Jun [1 ]
Song, Jia [1 ]
Liang, Xiao [1 ]
Yin, Yunzhi [1 ]
Zuo, Tiantian [1 ]
Chen, Daijie [1 ]
Shen, Qi [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Pharm, 800 Dongchuan Rd, Shanghai 200240, Peoples R China
关键词
alpha-napthtoflavone; breast cancer; CD44; CYP1B1; DTX; hyaluronic acid; lysosome escape; multidrug resistance; nanoparticles; polyethyleneimine; MESOPOROUS SILICA; ANTICANCER DRUGS; DELIVERY; DOCETAXEL; MICELLES; CYP1B1; CYTOCHROME-P450; PACLITAXEL; CELLS; FORMULATIONS;
D O I
10.2217/nnm-2018-0244
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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 alpha-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. [GRAPHICS]
引用
收藏
页码:447 / 464
页数:18
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