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Biofunctionalized Prussian Blue Nanoparticles for Multimodal Molecular Imaging Applications
Published on: April 28, 2015
Prussian blue nanoparticles targeting multiple PANoptosome-mediated PANoptosis for myocardial ischemia-reperfusion
Lingling Xu1,2, Lixian Jiang1,2, Rongrong Wu1,2
1Department of Ultrasound in Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
Abstract:
The extensive crosstalk among pyroptosis, apoptosis, and necroptosis limits the efficacy of therapies targeting only one pathway. Here, we show that Prussian blue (PB) nanoparticles act as multi-target PANoptosis inhibitors by binding key PANoptosome components including RIPK1, ZBP1, and AIM2 through multimodal interactions, thereby concurrently suppressing pyroptosis, apoptosis, and necroptosis in myocardial ischemia-reperfusion injury (MIRI). Platelet membrane-coated PB nanoparticles (PB@PM) exhibit enhanced cardiac targeting and efficiently alleviate MIRI-induced cardiac dysfunction, adverse ventricular remodeling, and cardiomyocyte hypertrophy. Mechanistically, PB@PM disrupt PANoptosome assembly, scavenge reactive oxygen species, improve mitochondrial function, and restore immune-inflammatory homeostasis. By integrating single nucleus transcriptomics of human heart samples, molecular dynamics simulations, transcriptomics, medical imaging, and molecular validation, we systematically decipher the therapeutic mechanisms of PB-based PANoptosis inhibition. This study establishes an integrative multi-omics framework for exploring PANoptosis in cardiovascular diseases and provides a promising nanotherapeutic strategy for MIRI treatment.
