N-acetylneuraminic acid and chondroitin sulfate modified nanomicelles with ROS-sensitive H2S donor via targeting E-selectin receptor and CD44 receptor for the efficient therapy of atherosclerosis

Currently, very limited therapeutic approaches are available for the drug treatment of atherosclerosis(AS). H2S-donor is becoming a common trend in much life-threatening research. Several studies have documented that H2S-lyase is predominantly present in endothelial cells. N-Acetylneuraminic acid (SA), natural carbohydrate, binds specifically to the E-selectin receptor of endothelial cells. Meanwhile, recent studies related to Chondroitin sulfate have excellent target binding ability with CD44 receptor. We conjecture that the N-Acetylneuraminic acid and Chondroitin sulfate modified nanomicelles not only enhances the accumulation of the drug but also cleaves the H2S donor in the lesion, thus one stone two birds. Given these findings, we synthesized two kinds of nanoparticles, Carrier I (SCCF) and Carrier II (SCTM), for atherosclerosis to validate our guesses. Initially, S-allyl-L-cysteine and 4-methoxyphenylthiourea were used as H2S donors for SCCF and SCTM, respectively. After the introduction of ROS-sensitive groups. Then, micelles with N-Acetylneuraminic acid and Chondroitin sulfate were prepared to load rapamycin(RAP). Further, in atherosclerosis Oil Red O staining (ORO) results confirmed remarkable treatment effect with SCCF@RAP and SCTM@RAP. Thus, we conclude that the effect of dual-targeting nanomicelles with ROS-sensitive H2S donor based on N-Acetylneuraminic acid and Chondroitin sulfate will have a better role in atherosclerosis.