Upconversion nanoparticles for in vivo NIR light-induced Drug Release – LightinDR

Delivery systems, especially nanoscaled systems, that allow for a non-invasive control of the release of bioactive molecules in living organisms are highly sought after. Such approaches are not only of interest in basic sciences but they would also open exciting perspectives for the treatment of diseases. Indeed, precise spatial and temporal control of the release of the therapeutic agent (e.g. drugs, proteins, genes or siRNAs) would allow coordination between drug availability, biological rhythms and disease activities. Various strategies have been developed for triggering drug release by external stimuli, including light which is a particularly attractive source of stimulation. Light can be readily available and focused, allowing precise temporal and spatial definition of the stimulus. In addition, light exposure time and intensity can also be precisely controlled and, as a consequence, the strength of the stimulus can be modulated. The major goal of this proposal is to develop new functionalized nanoparticles to be able to deliver given biomolecules or drugs using Red or NIR light by upconversion-assisted photolysis. In particular, we wish to decorate upconverting nanoparticles (UC-NPs) with blue-light sensitive photo-cleavable linkers. Those new types of UC-NPs are built around organic chromophore-based systems that achieve efficient triplet-triplet annihilation (TTA)-based UC leading to emissive nanoparticle systems able to do an efficient red to blue upconversion. The in vitro and in vivo efficacy of upconversion assisted photolysis will be quantified with a photoactivatable pro-fluorescent strategy in order to develop the best nanomaterial for light-induced drug delivery. We believe that this new type of nanocarrier approach should allow precise spatial and temporal control of the release of the therapeutic agent (e.g. drugs, proteins…) and would allow coordination between drug availability, biological rhythms and disease activities in the future. During this project, a multidisciplinary consortium (with abilities in organic and NP synthesis, soft matter chemistry, photophysics, non-linear optics, pharmacology, toxicology and biovectorology) will develop the best prototype system to be able to liberate specifically a “therapeutic agent” in the human body using light and to test their efficacy in a body environment. In particular, we plan to liberate nonsteroidal anti-inflammatory drugs on mouse models of arthritis. This multidisciplinary approach could open opportunities to bring “smart” molecular design into the phototherapeutic window and ultimately to the realm of clinical use.