Prodrug nanosystem equipped with a sonosensitizer for combined chemotherapy and sonodynamic therapy of melanoma

Melanoma is a severe eruptive disease caused by melanocyte lesions and characterized by aggressive tumors, which has become one of the fastest evolving cancers worldwide, and its incidence and mortality rates have shown larger increases than Other types of cancers. Finding effective medicines has become an important topic in collaborative research. Many compounds have been removed from clinical application because of poor physicochemical properties, especially low solubility, a high clearance rate and toxic side effects. In this study, a Reactive Oxygen Species (ROS)-responsive camptothecin (CPT) prodrug delivery system (CTS-S-CPT@IR 780 NPs) in which CPT was conjugated to chitosan was developed. The synthesized CTS-S-CPT conjugate self-assembled to form NPs loading IR 780 in solution. Sonodynamic therapy (SDT) at the tumor site can activate the sonosensitizer IR 780 to release large amounts of ROS and heat, inducing Apoptosis. ROS can also cleave carbon‒sulfur bonds and release the chemotherapeutic drug CPT. ROS-responsive CTS-S-CPT@IR 780 NPs activated by combination chemotherapy/SDT were successfully prepared for tumor-targeted drug delivery and can effectively inhibit tumor growth in vivo and in vitro with lower toxic side effects, and localized, controllable, and on-demand release drug. This prodrug approach has spawned hope for overcoming such treatment dilemmas.

3D cell spheroid; Drug delivery; Melanoma; Prodrug; Sonodynamic therapy.