Intravenous treatment of choroidal neovascularization by photo-targeted nanoparticles

Choroidal neovascularization (CNV) is the major cause of vision loss in wet age-related macular degeneration (AMD). Current therapies require repeated intravitreal injections, which are painful and can cause infection, bleeding, and retinal detachment. Here we develop nanoparticles (NP-[CPP]) that can be administered intravenously and allow local drug delivery to the diseased choroid via light-triggered targeting. NP-[CPP] is formed by PEG-PLA chains modified with a cell penetrating peptide (CPP). Attachment of a DEACM photocleavable group to the CPP inhibits cellular uptake of NP-[CPP]. Irradiation with blue light cleaves DEACM from the CPP, allowing the CPP to migrate from the NP core to the surface, rendering it active. In mice with laser-induced CNV, intravenous injection of NP-[CPP] coupled to irradiation of the eye allows NP accumulation in the neovascular lesions. When loaded with doxorubicin, irradiated NP-[CPP] significantly reduces neovascular lesion size. We propose a strategy for non-invasive treatment of CNV and enhanced drug accumulation specifically in diseased areas of the eye.