Verteporfin-mediated on/off photoswitching functions synergistically to treat choroidal vascular diseases

Choroidal vascular diseases,such as age-related macular degeneration,are the leading cause of vision impairment and are characterized by pathological angiogenesis.Verteporfin-mediated photodynamic therapy is a current strategy that selectively occludes choroidal neovasculature.However,the clinically used large-dose systemic administration increases the risk of systemic adverse events,such as phototoxicity to superficial tissues.In this study,we developed an in situ verteporfin delivery system with a photoswitching synergistic function that disassembles in response to intraocular inflammatory enzymes.Under light-on conditions,verteporfin-mediated photodynamic therapy effectively occurs and this leads to vascular occlusion.Under light-off conditions,non-photoactive verteporfin negatively regulates vascular endothelial growth factor-induced angiogenesis as a yes-associated protein inhibitor.Taken together,our system serves as an intraocular verteporfin reservoir to improve the bioavailability of verteporfin by innovatively exploiting its photochemical and biological functions.This work provides a promising strategy with synergistic antiangiogenic effects for the treatment of choroidal vascular diseases.