Evaluation of the Therapeutic Efficacy of a Nanostructured Inorganic Complex Combined with Monoamine Oxidase-A Inhibition in the Treatment of Non-Muscle Invasive Bladder Cancer

• Grant number: 25/01624-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2025
• End date: March 31, 2029
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Wagner José Fávaro
• Grantee: Gabriela Cardoso de Arruda Camargo
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Non-Muscle Invasive Bladder Cancer (NMIBC) is one of the major challenges in oncology, characterized by high recurrence and progression rates, particularly in patients refractory to BCG immunotherapy. Approximately 50% of patients fail to respond to BCG treatment, facing limited therapeutic options and a significant risk of progression to more aggressive stages. This project proposes an innovative approach through the development of ImmunoClor, a therapeutic compound that combines a nanostructured inorganic complex (CIN-1) with the selective monoamine oxidase-A inhibitor (MAO-AI) to overcome the limitations of current therapies. MAO-A is an emerging therapeutic target, with evidence of its role in tumorigenesis through the production of reactive oxygen species (ROS), immunosuppression within the tumor microenvironment (TME), and promotion of tumor progression. Its inhibition has demonstrated potential to reprogram tumor-associated macrophages, reduce cellular proliferation, and enhance the efficacy of immunotherapies. CIN-1, in turn, is an advanced nanostructured platform designed to optimize drug delivery, modulate immunological and metabolic pathways, and reverse tumor resistance, creating a synergistic effect with MAO-AI. The proposed study adopts a multidimensional approach, including physicochemical characterizations of ImmunoClor, cytotoxicity evaluations in tumor cell lines, ROS production analyses, and preclinical trials in chemically induced NMIBC animal models. The compound's impact on key biomarkers involved in immunological response, immune checkpoints, and metabolic pathways associated with glycolysis and oxidative phosphorylation will be investigated. ImmunoClor is expected to provide an effective therapeutic alternative to address current limitations, promoting a robust and sustained antitumor response. The project's impact transcends scientific advancements, offering an economically viable and accessible solution aligned with the needs of the Brazilian Unified Health System (SUS). It has the potential to reduce treatment-related costs and expand access to advanced therapies. By integrating innovation, social impact, and economic feasibility, this project lays the groundwork for a replicable model applicable to other malignancies, contributing to translational medicine and significant advancements in global oncology treatment.