CD44 aptamer mediated cargo delivery to lysosomes of retinal pigment epithelial cells to prevent age-related macular degeneration

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Chandola , C , Casteleijn , M G , Chandola , U M , Gopalan , L N , Urtti , A & Neerathilingam , M 2019 , ' CD44 aptamer mediated cargo delivery to lysosomes of retinal pigment epithelial cells to prevent age-related macular degeneration ' , Biochemistry and Biophysics Reports , vol. 18 , 100642 . https://doi.org/10.1016/j.bbrep.2019.100642

Title: CD44 aptamer mediated cargo delivery to lysosomes of retinal pigment epithelial cells to prevent age-related macular degeneration
Author: Chandola, C.; Casteleijn, M.G.; Chandola, U.M.; Gopalan, L.N.; Urtti, A.; Neerathilingam, M.
Other contributor: University of Helsinki, Division of Pharmaceutical Biosciences
University of Helsinki, Drug Research Program



Date: 2019
Language: eng
Belongs to series: Biochemistry and Biophysics Reports
ISSN: 2405-5808
DOI: https://doi.org/10.1016/j.bbrep.2019.100642
URI: http://hdl.handle.net/10138/312714
Abstract: Age related macular degeneration (AMD) is a progressive, neurodegenerative disorder that leads to the severe loss of central vision in elderlies. The health of retinal pigment epithelial (RPE) cells is critical for the onset of AMD. Chronic oxidative stress along with loss of lysosomal activity is a major cause for RPE cell death during AMD. Hence, development of a molecule for targeted lysosomal delivery of therapeutic protein/drugs in RPE cells is important to prevent RPE cell death during AMD. Using human RPE cell line (ARPE-19 cells) as a study model, we confirmed that hydrogen peroxide (H2O2) induced oxidative stress results in CD44 cell surface receptor overexpression in RPE cells; hence, an important target for specific delivery to RPE cells during oxidative stress. We also demonstrate that the known nucleic acid CD44 aptamer - conjugated with a fluorescent probe (FITC) - is delivered into the lysosomes of CD44 expressing ARPE-19 cells. Hence, as a proof of concept, we demonstrate that CD44 aptamer may be used for lysosomal delivery of cargo to RPE cells under oxidative stress, similar to AMD condition. Since oxidative stress may induce wet and dry AMD, both, along with proliferative vitreoretinopathy, CD44 aptamer may be applicable as a carrier for targeted lysosomal delivery of therapeutic cargoes in ocular diseases showing oxidative stress in RPE cells. © 2019
Subject: Age-related macular degeneration
CD44 aptamer
Lysosomal delivery
Oxidative stress
RPE cells
Targeted delivery
aptamer
CD44 receptor
cell surface receptor
drug carrier
fluorescent dye
hydrogen peroxide
unclassified drug
age related macular degeneration
ARPE-19 cell line
Article
cell stress
cellular distribution
controlled study
drug delivery system
epithelium cell
human
human cell
internalization
intracellular transport
lysosome
oxidative stress
protein expression
retinal pigment epithelium
vitreoretinopathy
1182 Biochemistry, cell and molecular biology
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