The LITTLE project (LIght Targeting TooLs in ImmunothErapy) aims to develop new nanomedicine and reversible photopharmachological approaches, remotely and spatiotemporally controlled by light, for application
in cancer therapy. LITTLE focuses on the development of light controlled activators of molecular inhibitors of CD73, which is a recognized membrane key enzyme involved in cancer dependent immune evasion. The ability to impart light control on therapies against this target will lower side effects of the current systemic treatments
along with the inhibitors’ dosages while better the localized effect of the therapy. To tackle this scientific goal LITTLE is organized in two, independent yet complementary research objectives: RO1) Nanomedicine: light triggered liposomal delivery, by using liposome of different compositions decorated with molecular
photoswitches into the lipid layers, to access a visible light precise delivery. The interaction with light will induce a precise and on demand release of the payload’s inhibitors. A simultaneous release of therapeutic and imaging agents, in combination with Magnetic Resonance Imaging, will provide a complete theragnostic tool. RO2)
Photopharmachology: incorporation of molecular photoswitches into already known small CD73 inhibitors to achieve a UV and later a visible light reversible control over the activities (pharmacokinetic and pharmacodynamic) of these candidates toward CD73 inhibition. Both the nanomedicine and the
photopharmachological approaches will be investigated and completely characterized up to the pre-clinical in vitro studies to provide insights in cancer immunotherapy. If positive further investigations, in collaboration with biologists and clinicians, will be implemented to apply of photopharmachology in cancer immunotherapy.
LITTLE is a multidisciplinary project basing on organic chemistry and merging chemical physics, photopharmachology and biology to provide novel perspectives in cancer treatments