Facile fabrication of redox nanoparticles loaded with exosomal-miRNAs and resveratrol as glycation inhibitor in alleviating the progression and development of diabetic cataract.

Diabetic cataract (DC) represents a highly prevalent ocular manifestation resulting from diabetes often culminating in vision impairment among individuals with diabetes. Regrettably, the armamentarium of pharmaceutical interventions capable of both delaying and thwarting the onset of DC remains conspicuously sparse. Based on contemporary investigations, the pathogenesis of DC is prominently influenced by oxidative harm to the crystalline lens and the nonenzymatic glycosylation of lens proteins. Consequently, we have developed self-regenerating cerium oxide nanoparticles (CeO₂ NPs), enveloped with resveratrol (RSV) and exosomal-microRNA (miRNA) to alleviate the effects of DC in an in vitro model. Moreover, the inclusion of RSV within CeO₂ NPs serves a dual purpose. It can act as an antioxidant, minimizing glycation, and induce oxidative stress by effectively neutralizing reactive oxygen species (ROS). Additionally, it serves as a glycation inhibitor effectively preventing the cross-linking. Consequently, it helps minimize the glucose level in hemoglobin and inhibits the formation of advanced glycation end products (AGEs). Likewise, the CeO₂-exosomal-miRNA when treated alone found to slightly impede the viability of human lens epithelial cells (HLEC) and induce apoptosis by suppressing the expression of α-crystalline gene (CRYAA). Particularly, miRNAs target genes associated with oxidative stress pathways, protein glycation, and the generation of AGEs, hence preventing structural damage to lens proteins. Compared with CeO₂, RSV-CeO₂, and miRNA-RSV-CeO₂, the presence of miRNA-RSV-CeO₂ led to a significant decrease in hemoglobin glycation. Remarkably, miRNA-RSV-CeO₂ NPs attenuate the formation of malondialdehyde (MDA) and conjugated dienes (CD) with a relative value of 14.63 and 11.37 nmol/mg. As per the report, this method presents a promising opportunity to implement the proposed material combination for attenuating diabetic cataracts.