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Coassembly of hypoxia-sensitive macrocyclic amphiphiles and extracellular vesicles for targeted kidney injury imaging and therapy.
- Source :
-
Journal of nanobiotechnology [J Nanobiotechnology] 2021 Dec 27; Vol. 19 (1), pp. 451. Date of Electronic Publication: 2021 Dec 27. - Publication Year :
- 2021
-
Abstract
- Background: 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).<br />Results: 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 <subscript>4</subscript> β <subscript>1</subscript> and α <subscript>L</subscript> β <subscript>2</subscript> , 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.<br />Conclusion: 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.<br /> (© 2021. The Author(s).)
- Subjects :
- Acute Kidney Injury metabolism
Acute Kidney Injury pathology
Animals
Calixarenes chemistry
Calixarenes metabolism
Calixarenes pharmacology
Calixarenes therapeutic use
Cell Line
Epithelial Cells drug effects
Epithelial Cells metabolism
Extracellular Vesicles metabolism
Humans
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Indoles chemistry
Indoles metabolism
Indoles pharmacology
Indoles therapeutic use
Inflammation
Integrins metabolism
Macrocyclic Compounds metabolism
Macrocyclic Compounds pharmacology
Macrocyclic Compounds therapeutic use
Macrophages drug effects
Macrophages metabolism
Mice
NF-kappa B metabolism
Organometallic Compounds chemistry
Organometallic Compounds metabolism
Organometallic Compounds pharmacology
Organometallic Compounds therapeutic use
Signal Transduction drug effects
Surface-Active Agents metabolism
Surface-Active Agents pharmacology
Surface-Active Agents therapeutic use
Acute Kidney Injury diagnostic imaging
Acute Kidney Injury drug therapy
Cell Hypoxia drug effects
Extracellular Vesicles chemistry
Macrocyclic Compounds chemistry
Surface-Active Agents chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1477-3155
- Volume :
- 19
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of nanobiotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 34961540
- Full Text :
- https://doi.org/10.1186/s12951-021-01192-w