Intravenous treatment of choroidal neovascularization by photo-targeted nanoparticles

Yanfei Wang, Chi-Hsiu Liu, Tianjiao Ji, Manisha Mehta, Weiping Wang, Elizabeth Marino, Jing Chen and Daniel S. Kohane ()
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Yanfei Wang: Harvard Medical School
Chi-Hsiu Liu: Harvard Medical School
Tianjiao Ji: Harvard Medical School
Manisha Mehta: Harvard Medical School
Weiping Wang: Harvard Medical School
Elizabeth Marino: Harvard Medical School
Jing Chen: Harvard Medical School
Daniel S. Kohane: Harvard Medical School

Nature Communications, 2019, vol. 10, issue 1, 1-9

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-08690-4

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