title: Ligand-functionalized nanoparticles target endothelial cells in retinal capillaries after systemic application.
abstract: To date, diseases affecting vascular structures in the posterior eye are mostly treated by laser photocoagulation and multiple intraocular injections, procedures that destroy healthy tissue and can cause vision-threatening complications. To overcome these drawbacks, we investigate the feasibility of receptor-mediated nanoparticle targeting to capillary endothelial cells in the retina after i.v. application. Cell-binding studies using microvascular endothelial cells showed receptor-specific binding and cellular uptake of cyclo(RGDfC)-modified quantum dots via the αvβ3 integrin receptor. Conversely, Mueller cells and astrocytes, representing off-target cells located in the retina, revealed only negligible interaction with nanoparticles. In vivo experiments, using nude mice as the model organism, demonstrated a strong binding of the ligand-modified quantum dots in the choriocapillaris and intraretinal capillaries upon i.v. injection and 1-h circulation time. Nontargeted nanoparticles, in contrast, did not accumulate to a significant amount in the target tissue. The presented strategy of targeting integrin receptors in the retina could be of utmost value for future intervention in pathologies of the posterior eye, which are to date only accessible with difficulty.
authors.affiliation: Department of Pharmaceutical Technology, University of Regensburg, 93040 Regensburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Pollinger
authors.forename: Robert
authors.initials: R
authors.lastname: Hennig
authors.forename: Andreas
authors.initials: A
authors.lastname: Ohlmann
authors.forename: Rudolf
authors.initials: R
authors.lastname: Fuchshofer
authors.forename: Rebecca
authors.initials: R
authors.lastname: Wenzel
authors.forename: Miriam
authors.initials: M
authors.lastname: Breunig
authors.forename: Joerg
authors.initials: J
authors.lastname: Tessmar
authors.forename: Ernst R
authors.initials: ER
authors.lastname: Tamm
authors.forename: Achim
authors.initials: A
authors.lastname: Goepferich
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology; D002196:Capillaries / Q000378:metabolism*; D002478:Cells, Cultured; D002829:Choroid / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008024:Ligands; D008268:Macular Degeneration / Q000473:pathology; D008297:Male; D051379:Mice; D008833:Microcirculation; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D011485:Protein Binding; D045663:Quantum Dots; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism; D012171:Retinal Vessels / Q000378:metabolism*; D013997:Time Factors
chemical_list: D039302:Integrin alphaVbeta3; D008024:Ligands