Investigation of the impact of a photoactive ruthenium complex on 3D bioprinted target and bystander spheroids under continuous flow in a vascularized breast cancer model

• Grant number: 23/11239-6
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: February 01, 2024
• End date: January 31, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry
• Principal Investigator: Roberto Santana da Silva
• Grantee: Amanda Blanque Becceneri
• Supervisor: Ibrahim Tarik Ozbolat
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Pennsylvania State University, United States
• Associated to the scholarship: 20/03367-6 - Phototherapy using ruthenium-phthalocyanine complexes as generators of reactive oxygen and nitrogen species: study of the mechanism of action in vitro in different 2D and 3D models of cancer cells, BP.PD

Abstract

Cancer is a substantial global health challenge, and conventional treatments frequently exhibit limitations and undesirable effects. This underscores the need to explore different and innovative therapeutic approaches. Photodynamic therapy (PDT) offers a minimally invasive alternative treatment that can be combined with other treatments. Although the effect of PDT on target cells is already well-studied, the impact of PDT on bystander cells, which are not directly targeted but can be influenced by substances released from target cells, remains poorly understood. One of the essential components of PDT is the photosensitizer (PS), and metal complexes, such as ruthenium complexes, have demonstrated promise as PS due to their properties. However, evaluating new compounds with antitumoral potential is challenging, as many fail during clinical tests after extensive preclinical evaluations. Therefore, a deeper analysis of future treatments and a better understanding of the tumor microenvironment and its responses to treatment are essential. The techniques currently available have many limitations; however, a new innovative technology, 3D bioprinting, offers a solution by reconstructing organs and tissues with diverse cell types in a way that mimics their natural architecture and has the potential to improve preclinical testing. Therefore, this project aims to study the effects of a photoactivated ruthenium complex, RuNO2TPyP, on 3D bioprinted homotypic and heterotypic target and bystander spheroids. The investigation will be conducted using a vascularized breast cancer model under continuous drug flow conditions. In our ongoing work, the promising results of RuNO2TPyP as a PS for PDT against lung and breast cancer make it a suitable candidate for evaluation in a more relevant cancer model. By combining PDT, bioprinting, and metal-based PS, this study aims to provide insights into the development of new and more effective cancer therapies. (AU)