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Intravenous treatment of choroidal neovascularization by photo-targeted nanoparticles

Author

Listed:
  • 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)

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.

Suggested Citation

  • Yanfei Wang & Chi-Hsiu Liu & Tianjiao Ji & Manisha Mehta & Weiping Wang & Elizabeth Marino & Jing Chen & Daniel S. Kohane, 2019. "Intravenous treatment of choroidal neovascularization by photo-targeted nanoparticles," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08690-4
    DOI: 10.1038/s41467-019-08690-4
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