Development of nitric oxide and hydrogen sulfide releasing hydrogels for cardiovascular therapeutic applications

• Grant number: 25/11054-1
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: December 01, 2025
• End date: November 30, 2026
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
• Principal Investigator: Amedea Barozzi Seabra
• Grantee: Roberta Albino dos Reis
• Supervisor: Tanveer Tabish
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Institution abroad: University of Oxford, England
• Associated to the scholarship: 23/16363-7 - Duo-gasotransmitters for biomedical applications: bioformulation of nanoparticles containing Aspirin-NOSH, BP.PD

Abstract

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, driven by endothelial dysfunction, mitochondrial impairment, and inflammation. Nitric oxide (NO) and hydrogen sulfide (H¿S) are key endogenous gasotransmitters that modulate vasodilation, oxidative stress, and cellular bioenergetics. However, current delivery systems for NO and H¿S suffer from short release duration, instability, and systemic toxicity due to uncontrolled release. The lack of dual-delivery platforms that facilitate spatiotemporal control represents a significant gap in cardiovascular regenerative strategies. This project hypothesizes that a thiolated alginate hydrogel capable of releasing NO and H¿S in a controlled and sustained manner can protect mitochondrial function and modulate inflammation in vascular cells under hypoxia-reoxygenation and chronic stress. Preliminary data from Brazil (FAPESP 2023/16363-7) demonstrated promising physicochemical and release properties. The proposed work at the University of Oxford will advance biological validation. Key evaluations include NO/H¿S release kinetics via EPR spectroscopy under normoxic and hypoxic conditions, mitochondrial function (¿¿m, mPTP opening, ATP), oxidative stress markers (ROS) and inflammatory response (ICAM-1, VCAM-1, IL-6, TNF-¿). The study will differentiate between fast-release and sustained-release formulations targeting acute injury and chronic inflammation, respectively.Expected results will provide mechanistic insights into the crosstalk between NO and H¿S and support the translational potential of hydrogels. The project may lead to new patentable technologies and therapeutic approaches in cardiovascular medicine, while enabling advanced knowledge transfer to Brazilian research networks under the FAPESP Thematic Project (2022/14645-2). (AU)