Dual-targeting micelles with ROS-sensitive H2S donor based on Sialic acid and Chondroitin sulfate for atherosclerosis

Abstract Background: Currently, very limited therapeutic approaches are available for the drug treatment of atherosclerosis(AS). H 2 S-donor is becoming a common trend in much life-threatening research. Several studies have documented that H 2 S-lyase is predominantly present in endothelial cells. Sialic acid, 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 dual targeting of chondroitin sulfate and Sialic acid not only enhances the accumulation of the drug in the lesion but also cleaves the H 2 S donor, thus one stone two birds. Methods: 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 H 2 S donors for SCCF and SCTM, respectively. After the introduction of ROS-sensitive groups. Then, chondroitin sulfate as the modified matrix and Sialic acid as the targeting group, micelles were prepared to load rapamycin(RAP). Results: In the in vitro assay, micelles were significantly different under H 2 O 2 (1 mM) conditions. In the targeting test, the dual-target effect was superior to the other subgroups. treatment with SCCF@RAP and SCTM@RAP effect in AS is remarkable as confirmed via Oil Red O staining. Conclusions: Thus, we conclude that the effect of dual targeting nanomicelles with ROS-sensitive H 2 S donor will have a better role in atherosclerosis.