Mesenchymal Stem Cell Membrane‐Camouflaged Liposomes for Biomimetic Delivery of Cyclosporine A for Hepatic Ischemia‐Reperfusion Injury Prevention

• Published in: Advanced science Vol. 11; no. 32; pp. e2404171 - n/a
• Main Authors: Chen, Haitian, Yin, Wen, Yao, Kang, Liang, Jinliang, Cai, Jianye, Sui, Xin, Zhao, Xuegang, Zhang, Jiebin, Xiao, Jiaqi, Li, Rong, Liu, Qiuli, Yao, Jia, You, Guohua, Liu, Yasong, Jiang, Chenhao, Qiu, Xiaotong, Wang, Tingting, You, Qiang, Zhang, Yingcai, Yang, Mo, Zheng, Jun, Dai, Zong, Yang, Yang
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01.08.2024; John Wiley and Sons Inc; Wiley
• Subjects: Animals; Apoptosis; biomimetic delivery; Biomimetics - methods; Cyclosporine - administration & dosage; Cyclosporine - pharmacology; cyclosporine A; Disease Models, Animal; Drug Delivery Systems - methods; Drug dosages; Health care; Homeostasis; Ischemia; ischemia‐reperfusion injury; Liposomes; Liver; Liver - drug effects; Liver - metabolism; Male; Membranes; mesenchymal stem cell; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - metabolism; Mice; Mice, Inbred C57BL; Mitochondria; Particle size; Prevention; Proteins; Reperfusion Injury - prevention & control; ischemia‐reperfusion injury; mesenchymal stem cell; cyclosporine A; biomimetic delivery
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202404171

Hepatic ischemia‐reperfusion injury (HIRI) is a prevalent issue during liver resection and transplantation, with currently no cure or FDA‐approved therapy. A promising drug, Cyclosporin A (CsA), ameliorates HIRI by maintaining mitochondrial homeostasis but has systemic side effects due to its low bioavailability and high dosage requirements. This study introduces a biomimetic CsA delivery system that directly targets hepatic lesions using mesenchymal stem cell (MSC) membrane‐camouflaged liposomes. These hybrid nanovesicles (NVs), leveraging MSC‐derived proteins, demonstrate efficient inflammatory chemotaxis, transendothelial migration, and drug‐loading capacity. In a HIRI mouse model, the biomimetic NVs accumulated at liver injury sites entered hepatocytes, and significantly reduced liver damage and restore function using only one‐tenth of the CsA dose typically required. Proteomic analysis verifies the protection mechanism, which includes reactive oxygen species inhibition, preservation of mitochondrial integrity, and reduced cellular apoptosis, suggesting potential for this biomimetic strategy in HIRI intervention. This work develops a biomimetic cyclosporin A (CsA) delivery system targeting hepatic lesion sites by constructing mesenchymal stem cell membrane‐camouflaged liposomes. The constructed hybrid nanovesicles effectively reduce liver damage and restore liver function at a one‐tenth dose of free CsA, demonstrating the potential of the nanovesicles to address the current challenges of hepatic ischemia‐reperfusion injury intervention.