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

• Published in: Carbohydrate polymers 2022-08, Vol.290, p.119518-119518, Article 119518
• Main Authors: Chen, Qiang, Jia, Chaochao, Xu, Yingran, Jiang, Zhuanzhuan, Hu, Ting, Li, Conghu, Cheng, Xu
• Format: Article
• Language: English
• Subjects: Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Chitosan; Chitosan - therapeutic use; Cinnamaldehyde; Doxorubicin - pharmacology; Doxorubicin - therapeutic use; Drug Resistance, Neoplasm; Female; Humans; Hydrogen-Ion Concentration; MCF-7 Cells; Multidrug resistance; Nanoparticles; pH-sensitive
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2022.119518

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. [Display omitted] •Amphiphilic chitosan was synthesized and assembled into stability DCCA particles.•DCCA particles reverse surface charge that increase cellular uptake at pH 6.5.•DCCA particles respond to lower pH 5.0 that trigger DOX and CA release.•CA overcome tumor drugs resistance by decreasing ATP and PARP-1 levels.•DCCA particles enhance MDR tumor treatment and reduce side effects in vivo.