X-Ray Induced photodynamic therapy using ruthenium complexes as nitric oxide and singlet oxygen generating agents: chemical, photochemical, and biological studies in tumor and Non-tumor cells

• Grant number: 24/06347-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: February 01, 2025
• End date: October 31, 2026
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Roberto Santana da Silva
• Grantee: Eduardo Rodrigues da Silva
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Radiation therapy (RT) is effective in combating cancer, but tumor resistance can limit its efficacy. Combining RT with chemotherapy aims to reduce doses, but concerns arise regarding toxicity to normal tissues. Photodynamic therapy (PDT) emerges as a promising alternative, utilizing photosensitizers (PSs) activated by visible light to destroy tumor cells. Although effective in various cancer types such as bladder, skin, lung, esophagus, and cervix, PDT faces challenges such as cutaneous phototoxicity and the need for more selective agents. Combining PDT and RT shows potential but faces challenges in clinical application. X-ray induced photodynamic therapy (X-PDT) emerges as a possible solution, activating PSs with X-rays to generate reactive oxygen species (ROS), essential for eliminating neoplastic tissues. Researchers seek to develop species that absorb X-ray energy, reducing the risk of exposure and enabling the use of lower doses compared to conventional RT. In this project, our aim is to investigate the interaction between PDT and RT when combined, using X-PDT to activate PSs with cytotoxic potential in cancer cells and their normal counterparts. For this purpose, we will employ ruthenium-phthalocyanine complexes, such as [RuPc(4-pic)2] (Pc = phthalocyanine; 4-pic = 4-picolina), to generate ROS, and [RuPc(NO)(ONO)] to produce ROS and nitrogen species (RONs). Our objective is to evaluate the cytotoxic effect of these combined therapies through a comprehensive analysis, encompassing chemical, photochemical, photophysical, photobiological, and biochemical aspects in breast tumor cells such as MDA-MB-231, MCF-7, and in normal breast cells, MCF-10A, using 2D model. We will meticulously investigate the biological effects of the presence of nitric oxide (NO) and singlet oxygen, especially focusing on the induction of cell death by the combination of these therapies.