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

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). 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 α4β1 and αLβ2, 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. 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. Graphical Abstract

Biosynthetic Dendritic Cell-Exocytosed Aggregation-Induced Emission Nanoparticles for Synergistic Photodynamic Immunotherapy

“…We extracted and purified DEVs based on our previous publications. ,, The culture supernatant of DC2.4 cells was serially centrifuged to eliminate the cell debris and apoptotic bodies, sieved by 0.22 μm filters, and ultracentrifuged at 130000 g for another 2 h to gather the pellets. The collected DEVs were further purified by 2 h of ultracentrifugation in PBS.…”

In situ forming oxygen/ROS-responsive niche-like hydrogel enabling gelation-triggered chemotherapy and inhibition of metastasis

“…Notably, it is also a negative prognostic and predictive factor for patients with poor disease-free survival and local control [ 7 ], and it has thus become a central role in tumor physiology and cancer treatment. However, the very existence of hypoxia also provides a clue for tumor-selective diagnosis and therapy [ 8 , 9 ]. Many factors of the hypoxia-relevant pathway have been considered as good candidates for theranostic targets, such as reductase and hypoxia-inducible transcription factor 1 (HIF-1) [ 10 , 11 ].…”

Fluorophore-based host–guest assembly complexes for imaging and therapy

“…Since the assembly of fluorophores with macrocycles can improve their physicochemical properties, this strategy is currently widely applied not only for the construction of luminescent materials 48 and the modulation of fluorophore properties, 49,50 but also for designing and developing biomedical reagents. 51–55 For example, Cao and co-workers constructed various fluorescent supramolecular organic framework materials 56,57 through host–guest interactions, thus controlling and tuning their shape and size. Li et al successfully developed the supramolecular organic framework that can be employed for nucleic acid delivery 58 or to improve the safety of photodynamic therapy reagents and maintain anti-tumour efficacy.…”