Fabrication of GSH-responsive small-molecule and photosensitizer loaded carboxymethyl chitosan nanoparticles: Investigation of chemo-photothermal therapy and apoptosis mechanism in melanoma cells

ABSTRACT A nano-drug delivery system that is responsive to glutathione (GSH) and combines chemotherapy (CT) and photodynamic therapy (PDT) was designed precisely for treating melanoma. The carboxymethyl chitosan (CMC), a water-soluble and biocompatible nanocarrier, was used to load the chemotherapeutic small-molecule drug camptothecin (CPT) and the photosensitizer Rhodamine-B (RhB). The development of dual drug combo (CCR NPs) nanoparticles with a mean particle diameter of 170 ± 2.2   nm in aqueous solution has been achieved using ultrasonic self-assembly. Nanoparticle disintegration and camptothecin (CPT) release occur as CPT, sensitive to glutathione (GSH), breaks in cancer cells with excellent GSH levels. The RhB encapsulated in the CCR NPs was released quickly to attain successive CPT release. The CPT dramatically lowers tumor cell GSH levels, inhibiting the antioxidant effect of GSH on photosensitizers' ROS production capabilities and improving PDT synergistically. Nanoparticle diameter, zeta potential, and outstanding stability were all demonstrated by the CCR NPs. In vitro toxicity study on A375 human melanoma cells showed that CPT and RhB were highly selective (SI=4.25) and had a synergic effect (CI=0.24). Biochemical staining methods confirmed the morphological changes and nuclear damages. Apoptosis was confirmed by FITC-Annuxin V and PI staining by flow cytometer. Investigating drug delivery systems integrating RhB and CPT represents a valuable novel strategy for treating melanoma cancer.