Nitrosyl-ruthenium complexes in nanoparticulate release systems: measurement of specificity and cytotoxic evaluation

• Grant number: 22/10343-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2022
• End date: July 31, 2024
• 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

Nitric oxide (NO) is a biological messenger that is vitally important in many physiological processes, such as cardiovascular control, neural signaling and defense against microorganisms and tumors. In addition, NO is also anticancer, which would allow the use of NO donor compounds in clinical treatments. Based on the chemical and biological characteristics of the NO molecule, it is vital to search for systems capable of releasing NO, in a controlled way, in the biological system. One of the imminent possibilities involves ruthenium nitrosyl complexes, whose strategy would be to use a compound that is thermodynamically stable, but active when stimulated. However, one of the major challenges faced by the current therapy for the treatment of cancer is the lack of specificity of chemotherapeutics to tumor cells and the presence of drug resistance mechanisms. In this context, nanotechnology has shown advances in targeting drugs to their therapeutic target, with a consequent increase in therapeutic efficacy and reduction of adverse effects. In addition to the advantage of nanocarriers in providing drug targeting, these systems are capable of encapsulating drugs and protecting them from possible degradation and inactivation, prolonging the drug release profile and increasing blood circulation time. Aiming to use the anticancer potentiality of NO, this project has as general objective to synthesize species that can act as NO donor agents by reductimetric process. The specificity of these compounds will be achieved through the encapsulation of {Ru-NO}3+ type complexes obtained when the system is exposed in metastatic cells. The encapsulation will involve the development of nanoparticles, which subjected to stimulation will provide the release of these species. In these studies, the species cis-[Ru(NO)Cl(bpy)2] (bpy= 2,2'-bipyridine), cis-[RuCl(NO2)(bpy)2], cis-[Ru(bpy) 2 NO(L)]n+ (L=chloride, pyridine, 4-picoline, 4-acetylpyridine). The chemical and kinetic characterization of these systems will be evaluated by spectrophotometric and electrochemical techniques. Cytotoxicity experiments will be conducted with cancer cells and cell viability will be evaluated using the MTT method.