Ultrasmall Nanoparticles Regulate Immune Microenvironment by Activating IL‐33/ST2 to Alleviate Renal Ischemia‐Reperfusion Injury

• Published in: Advanced healthcare materials 2024-05, Vol.13 (13), p.e2303276-n/a
• Main Authors: Xu, Liyao, Xing, Zhaoyu, Yuan, Jiaxin, Han, Yaobao, Jiang, Zhilin, Han, Mengxiao, Hou, Xianao, Xing, Wei, Li, Zhen
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - drug therapy; Acute Kidney Injury - metabolism; Acute Kidney Injury - pathology; Animals; Biocompatibility; Cu2−xSe nanoparticles; Cyclic AMP response element-binding protein; Cytokines; Health services; IL‐33/ST2; immune microenvironment; Immune system; Inflammation; Inflammatory response; Injuries; Interleukin-1 Receptor-Like 1 Protein - metabolism; Interleukin-33 - metabolism; Ischemia; ischemia‐reperfusion injury; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Kidneys; Lymphocytes T; M2 macrophage polarization; Macrophages; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; Morbidity; Nanoparticles; Nanoparticles - chemistry; Protein kinase A; RAW 264.7 Cells; Reperfusion; Reperfusion Injury - drug therapy; Reperfusion Injury - immunology; Reperfusion Injury - metabolism; Signal transduction; Signal Transduction - drug effects
• ISSN: 2192-2640; 2192-2659; 2192-2659
• DOI: 10.1002/adhm.202303276

Renal ischemia‐reperfusion injury (IRI) is a common disease with high morbidity and mortality. Renal IRI can cause the disorder of immune microenvironment and reprograming the immune microenvironment to alleviate excessive inflammatory response is crucial for its treatment. Cytokine IL‐33 can improve the immune inflammatory microenvironment by modulating both innate and adaptive immune cells, and serve as an important target for modulating immune microenvironment of renal IRI. Herein, we report that bilobetin‐functionalized ultrasmall Cu2−xSe nanoparticles (i.e., CSPB NPs) can activate the PKA/p‐CREB/IL‐33/ST2 signaling pathway to regulate innate and adaptive immune cells for reprograming the immune microenvironment of IRI‐induced acute kidney injury. The biocompatible CSPB NPs can promote the polarization of M1‐like macrophages into M2‐like macrophages, and the expansion of ILC2 and Treg cells by activating IL‐33/ST2 to modulate the excessive immune inflammatory response of renal IRI. More importantly, they can rapidly accumulate at the injured kidney to significantly alleviate IRI. This work demonstrates that modulating the expression of cytokines to reprogram immune microenvironment has great potential in the treatment of renal IRI and other ischemic diseases. Bilobetin‐functionalized ultrasmall Cu2−xSe nanoparticles (i.e., CSPB NPs) can activate the PKA/p‐CREB/IL‐33/ST2 signaling pathway to regulate innate and adaptive immune cells for reprograming the immune microenvironment of ischemia‐reperfusion injury‐induced acute kidney injury (AKI) and alleviating AKI damage.