RADoTE · Remote-Activated Delivery of Therapeutic Exosomes (RADoTE) via an Injectable PEG Hydrogel Carrier

Remote-Activated Delivery of Therapeutic Exosomes (RADoTE) via an Injectable PEG Hydrogel Carrier

The overall objective of the RADoTE project was to develop a hydrogel system that would improve extracellular vesicle (EV)-based therapies. EVs are cell-derived particles that contain unique biological content derived from their parent cells, and they can be internalized by target cells. Several research studies have suggested that EVs derived from stem cells might help to heal diseased tissues, such as damaged cardiac tissue following a heart attack. These cell-free biological particles could be useful for both tissue regeneration and drug delivery applications. However, because EVs are very small (about 120 nm in size), when they are injected into the blood stream they are rapidly cleared away, minimizing the intended therapeutic effects. For this project, an injectable hydrogel-based delivery system was used to control where EVs were administered, while keeping them stabilized until release from the hydrogel. The hydrogels designed for this project were degraded by tissue-penetrating near-infrared (NIR) light, meaning hydrogel degradation and EV release could be triggered on-demand by applying NIR light from outside of the body. To achieve this, the hydrogels contained UV-degradable crosslinks and embedded upconversion nanoparticles (UCNPs) that locally convert NIR light to UV. UCNPs represent an exciting new type of nanomaterial that can be used as light transducers for both imaging and photochemistry applications. During this project, a NIR-degradable hydrogel system was developed and validated, a model bioluminescent EV system enabled quantification and verification of bioactivity, and EV stability in degradable hydrogels and controlled release were assessed. Overall, these results provided proof-of-concept demonstration that this type of technology could be used in the future for controlled EV delivery. As a MSCA fellow, I co-authored publications in Nature Communications, Advanced Materials, ACS Nano, and Chemical Science, all of which are open access articles. This ambitious project involved a collaboration with the National University of Singapore (NUS) to provide UCNPs as well as expertise and insight, but the majority of the work was possible due to the placement within the world-renowned Stevens Group at Imperial College London. Because of the interdisciplinary nature of the research plan, this diverse research group was the ideal host for this project. I benefited greatly from working alongside experts in chemistry, materials science, cell biology, and EV technologies.

Data: CORDIS, © European Union