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

Abstract

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.

Keywords: Anti-atherosclerosis; CD44 receptor; Chondroitin sulfate; E-selectin receptor; N-Acetylneuraminic acid; ROS-sensitive H(2)S donor.