Anti-VEGF-aptamer modified C-dots—a hybrid nanocomposite for topical treatment of ocular vascular disorders

Asaf Shoval ^1,2 Amos Markus ^1,2 Zhixin Zhou ³ Xia Liu ³ Rémi Cazelles ³ Itamar Willner ³ Yossi Mandel ^1,2

¹School of Optometry and Vision Science, Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel
²Bar Ilan Institute for Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat-Gan, Israel
³Institute of Chemistry, The Minerva Center for Biohybrid Complex Systems, The Hebrew University of Jerusalem, Jerusalem, Israel

The vascular endothelial growth factor (VEGF) induces pathological angiogenetic ocular diseases. It is a scientific challenge to develop carriers for the controlled release of inhibitors for VEGF present in the back of the eye domain. Carbon dots (C-dots) functionalized with the VEGF aptamer are introduced and the hybrid nanoparticles are used for ocular nanomedicine. The C-dots are applied as effective carriers of the anti-VEGF aptamer across the cornea, yielding therapeutic levels upon topical administration. The hybrids show no toxicity for both in vitro and in vivo murine animal model, and further enable noninvasive intraocular concentration monitoring through the C-dots inherent fluorescence. In addition, the hybrid C-dots effectively inhibit VEGF stimulated angiogenesis in choroidal blood vessels. This inhibition is comparable to two commercially available anti-VEGF drugs, bevacizumab and aflibercept. The hybrid aptamer modified C-dots provide a versatile nanomaterial to treat age-related macular degeneration and diabetic retinopathy.