Renal-Targeted Drug Delivery by Chitosan Oligosaccharide Micelles with HSA-Enriched Protein Corona for the Treatment of Ischemia/Reperfusion-Induced Acute Kidney Injury

• Published in: ACS applied materials & interfaces 2024-09, Vol.16 (37), p.49913-49925
• Main Authors: Nan, Simin, Che, Yujie, Gong, Tao, Zhang, Zhirong, Fu, Yao
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - drug therapy; Acute Kidney Injury - pathology; Animals; Chitosan - chemistry; Drug Carriers - chemistry; Drug Delivery Systems; Humans; Male; Mice; Micelles; Oligosaccharides - chemistry; Oligosaccharides - pharmacology; Protein Corona - chemistry; Protein Corona - metabolism; Reperfusion Injury - drug therapy; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Serum Albumin, Human - chemistry; Surfaces, Interfaces, and Applications
• ISSN: 1944-8244; 1944-8252; 1944-8252
• DOI: 10.1021/acsami.4c09665

Renal-specific nanoparticulate drug delivery systems have shown great potential in reducing systemic side effects and improving the safety and efficacy of treatments for renal diseases. Here, stearic acid-grafted chitosan oligosaccharide (COS-SA) was synthesized as a renal-targeted carrier due to the high affinity of the 2-glucosamine moiety on COS to the megalin receptor expressed on renal proximal tubular epithelial cells. Specifically, COS-SA/CLT micelles were prepared by encapsulating celastrol (CLT) with COS-SA, and different proportions of human serum albumin (HSA) were then adsorbed onto its surface to explore the interaction between the protein corona and cationic polymeric micelles. Our results showed that a multilayered protein corona, consisting of an inner “hard” corona and an outer “soft” corona, was formed on the surface of COS-SA/CLT@HSA8, which was beneficial in preventing its recognition and phagocytosis by macrophages. The formation of HSA protein corona on COS-SA/CLT micelles also increased its accumulation in the renal tubules. Furthermore, the electropositivity of COS-SA/CLT micelles affected the conformation of adsorbed proteins to various degrees. During the adsorption process, the protein corona on the surface of COS-SA/CLT@HSA1 was partially denatured. Overall, COS-SA/CLT and COS-SA/CLT@HSA micelles demonstrated sufficient safety with renal targeting potential, providing a viable strategy for the management of ischemia/reperfusion-induced acute kidney injury.