Choroidal neovascularization (CNV) is a major cause of vision loss consisting in the formation of new blood vessels in the choroid, a tissue layer within the eye in contact with the retina. Neovascularization eventually leads to impaired retinal structure and function, and irreversible blindness. Currently, CNV is treated by regular intraocular injections of drugs that inhibit development of new vessels or by laser irradiation, both bearing risks of side effects such as retinal detachment or retinal tissue ablation.
Wang et al. now report a light-sensitive polymeric nanoparticle for intravenous drug delivery and specific targeting of the choroid. Their nanoparticle is functionalized with a cell-penetrating peptide covalently bound to a photocleavable caging group that prevents nanoparticle activation in the body. The caging group is only cleaved within the eye upon irradiation with a low-phototoxicity light beam. Following exposure of the cell-penetrating peptide, the nanoparticles are taken up locally by the choroidal endothelial cells. The authors show that their strategy can deliver doxorubicin, a standard drug for intraocular treatment of CNV, to the choroid of CNV mouse models, resulting in a 46.1% reduction of neovessel formation in comparison with controls.