Antioxidant and anti-senescence supramolecular complexes for managing dry eye diseases.

Dry eye disease (DED) is a common ocular disorder that severely impairs daily life. Oxidative stress has been identified as a key pathogenic factor driving cellular senescence and corneal epithelial damage in DED. Herein, we developed a biocompatible supramolecular complex based on the host-guest interaction of TEMPO-modified β-cyclodextrin (TCD) and puerarin (Pue), designated as P@TCD, for managing DED. The P@TCD could mitigate the ROS accumulation, reduce DNA damage, promote cell cycle progression, and attenuate cellular senescence in the corneal epithelium, thus preventing the further deterioration of DED. In two DED mouse models, P@TCD demonstrated favorable therapeutic efficacy by reversing corneal epithelial defects, alleviating conjunctival damage, and accelerating lacrimal gland recovery, thereby restoring tear film homeostasis, especially improving tear film stability with TBUT values of more than 5.3 s, compared to the DED models of less than 2.8 s, which is even more than the Cycloome® of 3.7 s. These results suggested the considerable potential of this dual ROS scavenging strategy for the effective treatment of DED.