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. We developed a drug delivery system that can be administered intravenously and accumulate in the back of the eye by light-triggered targeting. Photo-targeted nanoparticles (NP-[CPP]) were formed from PEG-PLA chains modified with cell penetrating peptide (CPP). Cell uptake of NP-[CPP] was inactivated by attaching a photocleavable group DEACM to the CPP, which also placed [CPP] in the core of the nanoparticle, preventing it from interacting with cells. Irradiation with 400 nm (blue) light cleaved DEACM, releasing CPP from the NP core and rendering it active. This system was evaluated in mice with laser-induced CNV. After intravenous injection of NP-[CPP], irradiation at the eye cleaved DEACM, allowing NP accumulation in the choroidal neovascular lesions. NP-[CPP] with irradiation showed greater accumulation in neovascular lesions compared to the same nanoparticles without irradiation or nanoparticles without CPP. In the same mouse CNV model, NP-[CPP] loaded with doxorubicin significantly reduced neovascular lesion size. This phototriggered targeting strategy could allow non-invasive treatment of CNV and similar diseases, and enhance the proportion of drug in diseased areas of the eye vs. other healthy parts of the eye or body.

Photo-targeted nanoparticles for intravenous treatment of choroidal neovascularization

256th National Meeting (2018)

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