Autor: |
Qiang, Chen, Chaochao, Jia, Yingran, Xu, Zhuanzhuan, Jiang, Ting, Hu, Conghu, Li, Xu, Cheng |
Rok vydání: |
2022 |
Předmět: |
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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 |
Externí odkaz: |
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