BODIPY Photocage‐Based Injectable Hydrogel for Light‐Controlled Nanoparticle Release

ABSTRACT Light‐controlled release of therapeutics holds great promise for improving patient compliance with treatment plans against many leading diseases and could contribute to a better quality of life for people suffering from chronic conditions. However, insufficient tissue penetration of light largely limits the in vivo applications of photoresponsive therapeutics. With the aim to circumvent this limitation and to work within tissue depths that are pragmatically accessible to light, we developed an injectable and photodegradable hydrogel that could enable controlled drug delivery in subcutaneous tissue. In this work, we describe a hydrogel formulation consisting of a 2‐arm photocage bearing azide and a BCN‐terminated 4‐arm PEG. Gelation takes place in minutes upon mixing the two components via strain‐promoted azide‐alkyne cycloaddition (SPAAC). Both gel precursors are made water‐soluble and exhibit low viscosity prior to complete gelation, and the pre‐gel is easily injectable through 23G needles. Photocage photocleavage and consequent gel degradation could be precisely controlled with green light irradiation. We further showed that nanoparticles can be successfully encapsulated into the gel and subsequently photo‐released. The full operation process was demonstrated in an ex vivo porcine model and the acute biocompatibility of gel injection and degradation was evaluated in healthy human skin cultured ex vivo.