Abstract
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.
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