PEG-modified fullerene nanoparticles attenuate myocardial injury via dual modulation of inflammatory response and endothelial barrier restorationOA
Intimate immune hyperactivation and subsequent vascular endothelial dysfunction are involved in the main pathophysiology of heart failure(HF).However,existing treatments through immunomodulation and endothelial protection for HF are not fully developed.In this study,we introduced PEGylated C_(60)fullerene nanoparticles(FNPs-PEG2000,FPs)as a two-pronged strategy to mitigate myocardial injury in mice with HF via superior immunomodulation combined with endothelial barrier restoration.The FPs exhibit prolonged systemic circulation,potent reactive oxygen species(ROS)scavenging capacity,and biocompatibility.Mechanistically,FPs suppress M1-type macrophage polarization,inhibit macrophage pyroptosis via the caspase-1/GSDMD pathway blockade,and restore endothelial barrier integrity by stabilizing junctional proteins.In a murine post-infarction HF model,FPs significantly improve cardiac function(left ventricular ejection fraction:34.1%vs.19.2%in HF controls),reduce fibrosis,and normalize pathological markers.Single-cell transcriptomics further reveal FPs-driven immunomodulation(66.48%neutrophil reduction and 78.98%endothelial restoration)and pro-angiogenic gene activation.Collectively,FPs demonstrate a multimodal therapeutic mechanism by disrupting ROS-inflammation crosstalk,preserving endothelial barrier integrity,and promoting cardiac repair,thus offering a promising translational candidate for HF management.
Xin An;Yuan Xu;Haoyu Wang;Jiacheng Sun;Jingchao Liu;Mingming Zhen;Chunru Wang;Chunli Bai
Beijing National Laboratory for Molecular Sciences,Key Laboratory of Molecular Nanostructure and Nanotechnology,CAS Research/Education Center for Excellence in Molecular Sciences,Institute of Chemistry,Chinese Academy of Sciences,Beijing 100190,China University of Chinese Academy of Sciences,Beijing 100049,ChinaBeijing National Laboratory for Molecular Sciences,Key Laboratory of Molecular Nanostructure and Nanotechnology,CAS Research/Education Center for Excellence in Molecular Sciences,Institute of Chemistry,Chinese Academy of Sciences,Beijing 100190,China University of Chinese Academy of Sciences,Beijing 100049,ChinaBeijing National Laboratory for Molecular Sciences,Key Laboratory of Molecular Nanostructure and Nanotechnology,CAS Research/Education Center for Excellence in Molecular Sciences,Institute of Chemistry,Chinese Academy of Sciences,Beijing 100190,ChinaBeijing National Laboratory for Molecular Sciences,Key Laboratory of Molecular Nanostructure and Nanotechnology,CAS Research/Education Center for Excellence in Molecular Sciences,Institute of Chemistry,Chinese Academy of Sciences,Beijing 100190,China University of Chinese Academy of Sciences,Beijing 100049,ChinaBeijing National Laboratory for Molecular Sciences,Key Laboratory of Molecular Nanostructure and Nanotechnology,CAS Research/Education Center for Excellence in Molecular Sciences,Institute of Chemistry,Chinese Academy of Sciences,Beijing 100190,ChinaBeijing National Laboratory for Molecular Sciences,Key Laboratory of Molecular Nanostructure and Nanotechnology,CAS Research/Education Center for Excellence in Molecular Sciences,Institute of Chemistry,Chinese Academy of Sciences,Beijing 100190,China University of Chinese Academy of Sciences,Beijing 100049,ChinaBeijing National Laboratory for Molecular Sciences,Key Laboratory of Molecular Nanostructure and Nanotechnology,CAS Research/Education Center for Excellence in Molecular Sciences,Institute of Chemistry,Chinese Academy of Sciences,Beijing 100190,China University of Chinese Academy of Sciences,Beijing 100049,ChinaBeijing National Laboratory for Molecular Sciences,Key Laboratory of Molecular Nanostructure and Nanotechnology,CAS Research/Education Center for Excellence in Molecular Sciences,Institute of Chemistry,Chinese Academy of Sciences,Beijing 100190,China University of Chinese Academy of Sciences,Beijing 100049,China
医药卫生
fullereneinflammationmacrophageendothelial barrierheart failure
《Nano Research》 2026 (5)
P.858-875,18
supported by the National Key R&D Program of China(No.2022YFA1205900)the National Natural Science Foundation of China(Nos.52422202 and 52172055)the Youth Innovation Promotion Association of CAS(No.2022036)。
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