Executive Summary : | Photoresponsive CO and NO-releasing molecules (photoCORMs and photoNORMs) have gained interest for controlled release of CO and NO with spatio-temporal precision using externally regulated light stimuli. However, most systems rely on harmful UV irradiation, which limits their practical applications due to the minimum tissue penetration power of UV light. Therefore, there is a need for visible to NIR light-responsive photoCORMs and photoNORMs to ensure CO and NO release deep inside tumor tissue with minimal photodamage to healthy tissues. This proposal aims to investigate the therapeutic efficacy of CO and NO for the treatment of malignant tumors by designing NIR responsive photoCORMs/photoNORMs, ensuring active tumor targetability, real-time monitoring of CO and NO release, and fictionalizing photoCORMs and photoNORMs with polyethylene glycol linkage for biocompatibility and bio-availability. Using four different fluorescent chromophores, the proposal plans to photo-cage CO and NO gasotransmitters. After synthesizing the molecules, the proposal will perform photolysis, confocal microscopic cell imaging studies, evaluation of the photo released gasotransmitter's effect on cancer and normal cells, and in vivo delivery using mice models. The expected outcome will address long-lasting challenges in cancer treatment, including early detection, tumor-specific remotely controlled spatiotemporal treatment, improved pharmacokinetics, and better understanding of the mechanistic aspect of the gasotransmitter for cancer treatment. |