Targeting osteopontin with gold nanoparticles for enhanced molecular imaging in Kawasaki disease: in-depth mechanistic study of STAT3 signaling in Col1 regulation.

backgroundKawasaki disease (KD) is a primary cause of acquired heart disease in children, often leading to significant complications like coronary artery lesions and vasculitis. Despite the administration of standard treatments, 10–20% of patients remain unresponsive, emphasizing the necessity for the development of improved diagnostic and treatment modalities. Given the limitations of conventional imaging techniques, this study investigates the potential of molecular imaging using targeted nanoparticles. Here, the role of osteopontin (OPN) in macrophage-dependent vascular inflammation and cardiovascular pathology is examined, as it may be crucial in the context of KD.

methodsGold nanoparticles (Au NPs) were synthesized through an amidation reaction to create OPN-Au NPs and mIgG-Au NPs. These were characterized using transmission electron microscopy and UV-vis spectra data, and their cytotoxicity was evaluated via cell viability and flow cytometry. The targeting efficacy of OPN-Au NPs was tested in vivo using CT imaging in a Kawasaki disease animal model. Furthermore, the role of BMDM-derived OPN in primary cardiac fibroblast activation was investigated through gene knockout and molecular mechanism analysis. The action mechanism of STAT3 on the epigenetic regulation of Col1 induced by OPN was studied using dual-luciferase reporter assays and ChIP-PCR.

resultsThe Au NPs exhibited favorable optical properties and low cytotoxicity. In vivo CT imaging demonstrated the capacity of these NPs to enhance the imaging of coronary artery lesions. Furthermore, BMDM-derived OPN was demonstrated to regulate fibroblast function via STAT3 signaling. Dual-luciferase reporter assays and ChIP-PCR revealed that OPN-mediated STAT3 regulates the transcriptional expression of Col1 at the epigenetic level.

conclusionThe findings indicate the potential of molecular imaging using Au NPs for the early detection and diagnosis of KD. Of note, the research demonstrates the role of OPN in modulating fibroblast activation through STAT3 signaling and its influence on the epigenetic regulation of Col1. This provides critical insights into the immune cell-fibroblast interaction in cardiovascular diseases, offering prospects for more targeted and effective diagnostic and therapeutic strategies for KD.