Development of Cu-MOFs-based scintillators for X-ray photodynamic therapy: a mechanistic approach focused on cytotoxic evaluation in 2D and 3D tumor cells

• Grant number: 24/00345-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2025
• End date: December 31, 2026
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Roberto Santana da Silva
• Grantee: Igor Vinicius de França
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Photodynamic therapy (PDT) via X-rays is a promising technique for the treatment of oncological diseases, as this radiation penetrates deeper into tissues compared to PDT using light. Photosensitizers, mostly derived from porphyrins, play a crucial role in this therapy. Their advantages and limitations determine treatment efficiency. Thus, photosensitizers capable of controlled release of nitric oxide (NO) can induce planned cytotoxicity via reactive oxygen species (ROS) and NO in hypoxic cancer cells. In this context, this project aims to synthesize copper(I) metal-organic structures with the ability to store nitric oxide as new photosensitizers for application in photodynamic therapy. Structural modifications will be made to enhance their use in photodynamic therapy, particularly for cancer treatment. This innovative approach may improve the selectivity and efficacy of cancer treatment with fewer adverse effects than traditional therapies. The goal is the synthesis, characterization, and evaluation of new photosensitizers, involving different building blocks. Additionally, efforts will be made to determine the amounts of singlet oxygen and NO in the cell, assess the photochemical reactivity through X-ray irradiation, and couple antibodies to the molecular structure to increase selectivity in cancer cells. Other studies related to the theme will be explored, including toxicity studies in 2D and 3D cell lines, and the mechanism of action of these complexes in photodynamic therapy.