Nanocomposite biomaterials for sustained release of nitric oxide: modeling and optimization of personalized platforms changing biomedical applications

Abstract

Nitric oxide (NO), an endogenous free radical, plays a crucial role in controlling biological processes, such as vasodilation, tissue regeneration and repair, apoptosis and immune defense. Its application in regenerative and antitumor therapies stands out as promising for stimulating tissue regeneration and promoting anticancer responses. In this project, it is proposed to develop nanoparticles and hydrogels for two biomedical applications: antitumor (melanoma) and regenerative (cardiovascular system) therapies with NO-donating biomaterials. The second application is linked to the FAPESP Thematic project focused on the development of NO-releasing hydrogels for cardiovascular applications. The proposal covers the optimization of the synthesis of chitosan nanoparticles (NPs) loaded with NO donors, incorporation into alginate hydrogels, and physicochemical evaluation, including the determination of sustained NO release profiles. Advanced Planned Statistical Experimentation techniques will be used to design personalized nano/biosystem production processes, optimized for the proposed applications. Furthermore, the proposal extends to biological tests of cytotoxicity, tissue regeneration and immunotoxicity, focusing on the interaction of nano/biosystems with tumor and non-tumor skin cells, in addition to cardiomyocytes. The research aims to consolidate production platforms for biodegradable and biocompatible nano/biosystems, providing in-depth understanding of biological mechanisms of action. Expected results include significant advances in the transition from research to clinical applications, contributing to the development of innovative therapeutic strategies. With a BEPE/FAPESP proposal expected, the interdisciplinarity of the project, combining biomaterials and Planned Statistical Experimentation, represents a valuable contribution to the scientific community, advancing knowledge in nanotechnology applied to health and regenerative and anti-tumor therapies.