The Photodynamic Therapy of N-TiO2 and GOT Nanoparticles Enhances Chemotherapy Efficacy in Melanoma Preclinical Models

Abstract

Introduction: Melanoma is the most aggressive form of skin cancer, with a rising incidence and poor prognosis in advanced stages. Due to its resistance to conventional therapies, alternative approaches such as photodynamic therapy (PDT) are under active investigation. This study evaluated the potential of N-doped TiO₂ (N-TiO₂) and graphene oxide–TiO₂ (GOT) nanoparticles (NPs), alone or in combination with cisplatin (CDDT), with or without xenon-light activation, to enhance chemosensitivity in melanoma preclinical models.

Materials and Methods: F10 melanoma cells were treated with varying concentrations of N-TiO₂ and GOT NPs alone or combined with CDDT, under light and dark conditions. The viability and cytotoxicity of the cells were assessed. For in vivo experiments, tumors were induced in syngeneic mice, which subsequently received N-TiO₂, GOT, CDDT, or combination therapy with or without irradiation. After ten days of treatment, tumor volume reduction and pathological response were evaluated.

Results: Photoactivated N-TiO₂ and GOT NPs significantly enhanced the cytotoxic effects of CDDT and reduced melanoma cell proliferation and tumor growth. In vivo, treatment responses ranged from 50–55% for N-TiO2 + CDDT and 60–70% for GOT plus CDDT under PDT conditions. Histopathological analysis confirmed the absence of notable cytotoxic or metastatic effects on major organs, including the liver and spleen.

Conclusion: Photoactivated N-TiO₂ and GOT nanoparticles potentiated the antitumor effects of cisplatin, reduced tumor proliferation, and enhanced therapeutic responses in melanoma preclinical models. These findings suggest that PDT with N-TiO₂ or GOT NPs, in combination with chemotherapy, may be a promising alternative strategy for melanoma management.