Cornea-SELEX-derived DNA aptamers for preparing spherical nucleic acids and corneal staining

Topical eye drops suffer from poor bioavailability due to rapid tear clearance and corneal barriers, which limit their therapeutic efficacy. Aptamers offer a promising solution for targeted ocular delivery and extended drug retention time. In this study, we employed gold nanoparticles (AuNPs) functionalized with aptamers previously selected to bind to porcine corneal tissues, forming spherical nucleic acids (SNAs). The binding of the SNAs to corneal tissues and human corneal epithelial cells (HCECs) was investigated. A total of six different aptamers were tested, each with an extended poly-adenine tail to attach to AuNPs using the thermal evaporation method. Among the six SNAs, the one prepared using the Cornea-S5 aptamer exhibited the best colloidal stability and optimal binding to both corneal tissues and HCECs, and it can specifically stain scarred regions. Flow cytometry determined the dissociation constant of Cornea-S5 to HCECs to be 169 nM. These findings highlight the potential of aptamer-AuNP conjugates for precise ocular drug delivery and diagnostics.