CD44 Receptor-Targeted and Reactive Oxygen Species-Responsive H(2)S Donor Micelles Based on Hyaluronic Acid for the Therapy of Renal Ischemia/Reperfusion Injury

[Image: see text] For the therapy attenuating renal ischemia–reperfusion (IR) injury, a novel drug delivery system was urgently needed, which could precisely deliver drugs to the pathological renal tissue. Here, we have prepared new nanomaterials with a reactive oxygen species (ROS)-responsive hydrogen sulfide (H(2)S) donor and hyaluronic acid that targets CD44 receptor. The novel material was synthesized and characterized via related experiments. Then, rapamycin was loaded, which inhibited kidney damage. In the in vitro study, we found that the micelles had ROS-responsiveness, biocompatibility, and cell penetration. In addition, the experimental results showed that the intracellular H(2)S concentration after administration was threefold higher than that of the control group. The western blot assay revealed that they have anti-inflammatory effects via H(2)S donor blocking the NF-κB signaling pathway. Consequently, the rising CD44 receptor-targeting and ROS-sensitive H(2)S donor micelles would provide a promising way for renal IR injury. This work provides a strategy for improving ischemia/reperfusion injury for pharmaceuticals.