Oxaliplatin-chitosan nanoparticles induced intrinsic apoptotic signaling pathway: A “smart” drug delivery system to breast cancer cell therapy

• A “smart” pH-responsive DDS based on chitosan nano-carrier is developed.
• Oxaliplatin was released from the DDS more efficiently at pH 4.5 than at pH 7.4.
• The possible activation of intrinsic apoptotic signaling pathway was explored.
• The expression of Bax, Bik, Cyt C, Caspase-9 and -3 was significantly up-regulated.
• Bcl-2 and Survivin expression were inhibited in breast cancer (MCF-7) cells.

This study was to investigate “smart” pH-responsive drug delivery system (DDS) based on chitosan nano-carrier for its potential intelligent controlled release and enhancing chemotherapeutic efficiency of Oxalipaltin. Oxaliplatin was loaded onto chitosan by forming complexes with degradable to construct nano-carrier as a DDS. Oxaliplatin was released from the DDS much more rapidly at pH 4.5 than at pH 7.4, which is a desirable characteristic for tumor-targeted drug delivery. Furthermore, the possible intrinsic apoptotic signaling pathway was explored by Western blot. It was found that expression of Bax, Bik, cytochrome C, caspase-9 and -3 was significantly up-regulated while the Bcl-2 and Survivin were inhibited in breast cancer MCF-7 cells. For instance, nanoparticles inducing apoptosis in caspase-dependent manner indicate that chitosan nanoparticles could act as an efficient DDS importing Oxalipaltin to target cancer cells. These approaches suggest that “smart” Oxaliplatin delivery strategy is a promising approach to cancer therapy.

Oxaliplatin-loaded chitosan nanoparticles formation and in vitro delivery mechanisms into the MCF-7 cells. The strategy explains Oxp-CH-NPs effectively induce cytotoxicity via endocytosis process.Figure optionsDownload as PowerPoint slide