Targeted 8-arm PEG Nanosystems for Localization of Choroidal Neovascularization Macular Degeneration Model.
ACS Appl Bio Mater
; 7(8): 5496-5505, 2024 Aug 19.
Article
de En
| MEDLINE
| ID: mdl-39107259
ABSTRACT
8-arm PEG (polyethylene-glycol) is a highly promising nanoplatform due to its small size (<10 nm), ease-of-conjugation (many functionalized variants are readily available with "click-like" properties), biocompatibility, and optical inactivity. This study evaluates 8-arm PEG uptake into cells (in vitro) and localization and clearance in vasculature (in vivo) for targeting of choroidal neovascularization in mice, an animal model of macular degeneration. 8-arm PEG nanoparticles were labeled with fluorescein isothiocyanate (FITC) and functionalized in the absence or presence of pentameric Ar-Gly-Asp (RGD; 4 RGD motifs and a PGC linker), one of the most common peptide motifs used for active targeting. In vitro studies show that RGD-conjugated 8-arm PEG nanoparticles exhibit enhanced cellular uptake relative to non-RGD-conjugated control NPs at 34% ± 9%. Laser-induced choroidal neovascularization (CNV) was performed in a mouse model to measure 8-arm PEG localization and clearance to model macular degeneration lesions in vivo. It was determined that both RGD-conjugated and non-RGD-conjugated (nRGD) 8-arm PEG particles localized to CNV lesions, with a half-life around 24 h. In vivo experiments showed that RGD-conjugated nanoparticles exhibited enhanced localization by 15-20% relative to without RGD controls. Exhibiting a high rate of localization and fast clearance relative to larger nanoparticles, targeted 8-arm PEG nanoparticles with a conjugated RGD-peptide could be a promising modality for macular degeneration diagnosis and therapy.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Taille de particule
/
Polyéthylène glycols
/
Néovascularisation choroïdienne
/
Nanoparticules
/
Dégénérescence maculaire
Limites:
Animals
/
Humans
Langue:
En
Journal:
ACS Appl Bio Mater
Année:
2024
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique