Development of mitochondria-targeted nanomedicines for cardiovascular applications (360G-Wellcome-312718_Z_24_Z)

My vision for this award is to set the research agenda for the nascent but expanding field of mitochondria-targeted nanomedicines. This award will be used to generate proof-of-principle data and to strengthen my profile, thereby facilitating a transition towards my own independent multidisciplinary research group. The technology developed herein will be relevant across therapeutic fields, but this proposal will focus on preventing myocardial ischaemia/reperfusion (I/R) injury to improve outcomes following a heart attack. I/R injury is initiated by the mitochondrial production of reactive oxygen species. It is already established that nitric oxide (NO) delivered at the point of reperfusion reduces injury, but achieving this in practice is difficult. This project will synergistically build on my current work on NO- releasing graphene, specifically, it will (1) develop novel mitochondria- targeted, redox-responsive, NO-releasing graphene oxide (mitoNOGO); (2) demonstrate mitochondrial uptake of mitoNOGO; (3) generate proof-of-principle evidence of protection against I/R injury using in vitro and ex vivo models; and (4) build up my track-record to secure further research funding and progress towards academic independence. This project seeks to explore the synergy between engineering and cardiovascular biology. Ultimately, the knowledge generated could lead to future development of mitochondria-targeted therapeutics for the heart and other organs.