Coassembly of hypoxia-sensitive macrocyclic amphiphiles and extracellular vesicles for targeted kidney injury imaging and therapy

• Published in: Journal of nanobiotechnology Vol. 19; no. 1; pp. 451 - 21
• Main Authors: Cheng, Yuan-Qiu, Yue, Yu-Xin, Cao, Hong-Mei, Geng, Wen-Chao, Wang, Lan-Xing, Hu, Xin-Yue, Li, Hua-Bin, Bian, Qiang, Kong, Xiang-Lei, Liu, Jian-Feng, Kong, De-Ling, Guo, Dong-Sheng, Wang, Yue-Bing
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 27.12.2021; BioMed Central; BMC
• Subjects: Adenosine; Aluminum; Analysis; Animal models; Apoptosis; Care and treatment; Chronic kidney failure; Coassembly; Diagnosis; Epithelial cells; Epithelium; Extracellular vesicles; Fibrosis; Fluorescence; Hypoxia; Hypoxia-inducible factor 1a; Injuries; Ischemia; Kidney diseases; Kidney hypoxia; Kidneys; Macrocycles; Macrocyclic amphiphile; Macrophages; Medical imaging; Mesenchyme; Metabolism; NF-κB protein; Receptors; Reperfusion; Risk factors; Scientific imaging; Self-assembly; Signal transduction; Sodium; Stem cells; Supramolecular chemistry; Vesicles; China; Coassembly; Extracellular vesicles; Macrocyclic amphiphile; Kidney hypoxia; Supramolecular chemistry
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-021-01192-w

Hypoxia is a major contributor to global kidney diseases. Targeting hypoxia is a promising therapeutic option against both acute kidney injury and chronic kidney disease; however, an effective strategy that can achieve simultaneous targeted kidney hypoxia imaging and therapy has yet to be established. Herein, we fabricated a unique nano-sized hypoxia-sensitive coassembly (Pc/C5A@EVs) via molecular recognition and self-assembly, which is composed of the macrocyclic amphiphile C5A, the commercial dye sulfonated aluminum phthalocyanine (Pc) and mesenchymal stem cell-excreted extracellular vesicles (MSC-EVs). In murine models of unilateral or bilateral ischemia/reperfusion injury, MSC-EVs protected the Pc/C5A complex from immune metabolism, prolonged the circulation time of the complex, and specifically led Pc/C5A to hypoxic kidneys via surface integrin receptor α β and α β , where Pc/C5A released the near-infrared fluorescence of Pc and achieved enhanced hypoxia-sensitive imaging. Meanwhile, the coassembly significantly recovered kidney function by attenuating cell apoptosis, inhibiting the progression of renal fibrosis and reducing tubulointerstitial inflammation. Mechanistically, the Pc/C5A coassembly induced M1-to-M2 macrophage transition by inhibiting the HIF-1α expression in hypoxic renal tubular epithelial cells (TECs) and downstream NF-κB signaling pathway to exert their regenerative effects. This synergetic nanoscale coassembly with great translational potential provides a novel strategy for precise kidney hypoxia diagnosis and efficient kidney injury treatment. Furthermore, our strategy of coassembling exogenous macrocyclic receptors with endogenous cell-derived membranous structures may offer a functional platform to address multiple clinical needs.