Combining sodium chloride nanoparticle osmolarity spikes with irinotecan chemotherapy to amplify oxidative stress in the treatment of colorectal cancer

초록

Sodium chloride nanoparticles (SCNPs) have potential utility in anticancer treatment. When these nanoparticles enter a cell through endocytosis and disrupt cellular homeostasis, an osmotic spike is triggered inside the cell. This causes the generation of reactive oxygen species (ROS), ultimately leading to tumor cell death. We developed SCNPs and coated them with PLGA to create SC@PLGA-NPs. These were then encapsulated in lipids to produce SC@PLGA-LPs. We then incorporated irinotecan (CPT-11), resulting in the creation of SC@PLGA/CPT11-LPs for use in the treatment of colorectal cancer. The in vitro data confirmed the successful encapsulation and release of SCNPs. This resulted in increased osmotic pressure and ROS generation. The addition of CPT-11 to SCNPs further increased ROS production. Finally, these effects, combined with the topoisomerase I inhibitory mechanism of CPT-11, resulted in the apoptosis of HT-29 cells. Intratumoral injection of SC@PLGA/CPT-11-LPs into an HT-29 xenograft mouse model provided in vivo confirmation that this is a reliable and effective method for the delivery of NPs and drugs.

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