Dual-pH responsive chitosan nanoparticles for improving in vivo drugs delivery and chemoresistance in breast cancer

被引：54
作者：
Chen, Qiang [1 ]
Jia, Chaochao [1 ]
Xu, Yingran [1 ]
Jiang, Zhuanzhuan [1 ]
Hu, Ting [1 ,2 ]
Li, Conghu [1 ,2 ]
Cheng, Xu [1 ,2 ]
机构：
[1] Anqing Normal Univ, Sch Life Sci, Anqing 246052, Peoples R China
[2] Prov Key Lab Biodivers Study & Ecol Conservat Sou, Anqing 246133, Peoples R China
来源：
CARBOHYDRATE POLYMERS | 2022年 / 290卷
关键词：
Chitosan; Nanoparticles; Cinnamaldehyde; pH; -sensitive; Multidrug resistance; TUMOR; DOXORUBICIN; RESISTANCE; ACID; CYTOTOXICITY; NANOGELS; ENHANCE;
D O I：
10.1016/j.carbpol.2022.119518
中图分类号：
O69 [应用化学];
学科分类号：
081704 ;
摘要：
Efficient intracellular drugs delivery and accumulation are the key determinant for overcoming tumor multidrug resistance (MDR). To realize this purpose, dual-pH responsive chitosan nanoparticles (DCCA/DOX-NPs) were fabricated to treat MDR tumor in human breast cancer (MCF-7/ADR). The particles were firstly sensitive to tumor extracellular pH 6.5, contributing to the surface charge reversal (6.32 -> 11.45 mV) by the cleavage of beta-carboxylic amide, which greatly increased cellular uptake efficiency. DCCA/DOX-NPs further responded to lower intracellular pH 5.0, thereby triggering DOX and cinnamaldehyde (CA) release by the cleavage of Schiff base. Cells assays verified that dual-pH sensitive particles caused higher toxicity in MDR tumor cells. Furthermore, the particles could overcome tumor resistance by decreasing intracellular levels of ATP and PARP-1, eventually receiving stronger antitumor efficiency in vivo (84.94%). Overall, this amphiphilic chitosan nanosystem with various bioactivities could work as an alternative promising for treating MDR tumor.
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页数：13
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