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

Autor: Qiang, Chen, Chaochao, Jia, Yingran, Xu, Zhuanzhuan, Jiang, Ting, Hu, Conghu, Li, Xu, Cheng
Rok vydání: 2022
Předmět:
Zdroj: Carbohydrate Polymers. 290:119518
ISSN: 0144-8617
DOI: 10.1016/j.carbpol.2022.119518
Popis: 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 β-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.
Databáze: OpenAIRE