A Supramolecular\nDeferoxamine–Crisaborole Nanoparticle\nTargets Ferroptosis, Inflammation, and Oxidative Stress in the Treatment\nof Retinal Ischemia/Reperfusion Injury

Retinal ischemia–reperfusion (IR) injury is a\nmajor cause\nof vision loss worldwide, with ferroptosis, oxidative stress, and\ninflammation playing key roles in its pathogenesis. Currently, treatments\ntargeting multiple aspects of this condition are limited. This study\nintroduces a supramolecular nanoparticle combining the phosphodiesterase\n4 (PDE4) inhibitor crisaborole and the ferroptosis inhibitor deferoxamine\nto address these pathological processes. Crisaborole forms a dynamic\nbond with deferoxamine via benzoxaborole–catechol chemistry,\ncreating an amphiphilic molecule that assembles into nanoparticles.\nTreatment with these nanoparticles enhances glutathione peroxidase\n4 (GPX4) levels, downregulates ferroptosis-related genes [Acyl-CoA\nsynthetase long chain family member 4 (<i>Acsl4</i>), heme\noxygenase 1 (<i>Hmox1</i>)], reduces inflammatory markers\n(interleukin-1 beta, interleukin-6, tumor necrosis factor alpha),\nand decreases reactive oxygen species. Electroretinogram and histochemical\nanalysis confirm the nanoparticles’ superior protective effects\ncompared to control treatments. This study proposes a novel nanoparticle\napproach for retinal IR injury by simultaneously targeting multiple\npathogenic pathways.