Carbon Quantum Dot Permeation Through the Bovine Blood-Retina Barrier

Tissue barriers severely limit the delivery of drugs and imaging agents, contributing to suboptimal diagnostic and therapeutic efficacy. Carbon quantum dots (CQDs) have emerged as promising alternatives to conventional contrast agents and theranostic carriers due to their intrinsic luminescence, facile functionalization, and biocompatibility. Here, we synthesized CQDs with distinct surface charges and evaluated their transport across an in vitro endothelial barrier. Negatively charged CQDs exhibited significantly faster and greater translocation across the barrier than positively charged counterparts. We further investigated barrier penetration across the blood-retina barrier (BRB), an experimentally accessible model sharing structural and functional similarities with the blood-brain barrier (BBB). Using ex vivo bovine eyes, CQD solution was applied to the posterior eye, and photoluminescence spectra from neural retina and choroid tissues were collected pre- and post-treatment. Under 430 nm excitation, negatively charged CQDs displayed a characteristic emission peak at 542 nm. Untreated retina showed negligible fluorescence, whereas treated retina exhibited a prominent 542 nm peak. In the choroid, CQD treatment yielded three emission peaks at 500, 542, and 590 nm, respectively. In comparison, treatment with positively charged CQDs showed no differences in the retina and choroid. These results collectively demonstrate that negatively charged CQDs can permeate the neural retina and reach the choroid, highlighting their potential to cross restrictive biological barriers such as the BBB even without additional surface modification.