Intravenous treatment of choroidal neovascularization by photo-targeted nanoparticles

Nat Commun. 2019 Feb 18;10(1):804. doi: 10.1038/s41467-019-08690-4.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Intravenous
  • Animals
  • Cell-Penetrating Peptides / chemistry
  • Choroidal Neovascularization / drug therapy*
  • Choroidal Neovascularization / therapy
  • Coumarins / chemistry
  • Disease Models, Animal
  • Doxorubicin / administration & dosage
  • Doxorubicin / pharmacokinetics
  • Drug Delivery Systems / methods
  • Female
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Light
  • Mice, Inbred C57BL
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry*
  • Phototherapy / methods
  • Polyethylene Glycols
  • Tissue Distribution

Substances

  • Cell-Penetrating Peptides
  • Coumarins
  • monomethoxypolyethyleneglycol-polylactide block copolymer
  • Polyethylene Glycols
  • Doxorubicin
  • 4-methyl-7-diethylaminocoumarin