Influence of melanin on the sensitivity and cellular phenotype of human melanoma treated with photodynamic therapy

• Grant number: 24/18375-5
• Support Opportunities: Scholarships in Brazil - Program to Stimulate Scientific Vocations
• Start date: February 24, 2025
• End date: April 12, 2025
• Field of knowledge: Biological Sciences - Biophysics - Cellular Biophysics
• Principal Investigator: Vanderlei Salvador Bagnato
• Grantee: Isabella Bastos Reis
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Photodynamic therapy (PDT) is a promising technic for treating malignant neoplasms and premalignant lesions, particularly in the skin. Over the past two decades, advancements in basic research and multicenter clinical studies have facilitated the integration of PDT into clinical settings for non-melanoma skin cancers (NMSC). While PDT is well-established for NMSC treatment, its application in melanoma remains less understood. Melanoma is characterized by extreme heterogeneity and presents unfavorable optical properties due to melanin content, complicating PDT's efficacy. Current literature lacks a consensus on PDT's antitumor effects in melanoma, highlighting the need for further investigation into the impact of melanin on treatment outcomes. The abundance of the pigment is one of the important factors to be investigated, given its interference in the photophysical and photochemical processes that determine the tumor damage of PDT. Thus, this project aims to analyze the influence of melanin on the sensitivity and cell phenotype of human melanoma treated with PDT. For this purpose, a lineage of amelanotic human melanoma A-375 (ATCC® CRL-1619¿) and melanotic SH-4 (ATCC® CRL-7724¿) will be used. For the PDT, the photosensitizing agents used will be Photogem® (Moscow, Russia) and Photodithazine® (Veta-Grand, Russia), along with their respective excitation systems: 630 nm and 660nm (5 J/cm2). The cytotoxicity of the treatment, the pattern of death, the proliferative capacity of the cells after treatment, and the stage of the cell cycle will be tested. These data will highlight the effect of PDT on human melanoma with different patterns of melanogenesis and their respective resulting phenotypes, indicating new routes for PDT in melanoma. This study is within the traditional research lines of the Optics Group (IFSC-USP) and is being planned for execution during the 50-day internship program.