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二茂铁功能化黑磷纳米平台实现动脉粥样硬化斑块的靶向和长效磁共振成像可视化

Ferrocene-Functionalized Black Phosphorus Nanoplatform Enables Targeted and Prolonged MRI Visualization of Atherosclerotic Plaques.

作者信息

Huang Xiao, Zhao Yuanyuan, Zhou Miao, Guo Yukang, Wang Haiyun, Chen Yuanyuan, Peng Jian

机构信息

Institute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, 430065, China.

Institute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, 430065, China.

出版信息

Adv Sci (Weinh). 2025 Aug;12(32):e03654. doi: 10.1002/advs.202503654. Epub 2025 Jun 5.

Abstract

Despite the critical role of contrast-enhanced magnetic resonance imaging (MRI) in clinical diagnostics, current contrast agents face dual challenges: metallic formulations provoke biosafety concerns while organic radicals exhibit transient imaging windows. To overcome these limitations, a radical-engineered 2D black phosphorus (2D BP) nanoplatform is reported through atomic-scale conjugation of aminoferrocene, creating a stable complex with enhanced electron spin resonance, named FcP. The covalent coupling strategy establishes persistent T-weighted contrast capability. Subsequent hyaluronic acid (HA) functionalization endows the HA-FcP system with CD44-specific targeting, achieving 1.7-fold higher plaque accumulation than non-targeted counterparts in apolipoprotein E-deficient models. Remarkably, this nanostructure enables continuous MRI visualization of atherosclerotic lesions for 120 h post-injection. Systematic biosafety evaluation demonstrates >90% cell viability and normal hematological parameters. This work pioneers a new paradigm for MRI contrast agents through spin state manipulation of 2D materials, providing a translational platform for precision cardiovascular diagnostics.

摘要

尽管对比增强磁共振成像(MRI)在临床诊断中起着关键作用,但目前的造影剂面临双重挑战:金属制剂引发生物安全问题,而有机自由基的成像窗口短暂。为了克服这些限制,通过氨基二茂铁的原子级共轭报道了一种自由基工程二维黑磷(2D BP)纳米平台,形成了一种具有增强电子自旋共振的稳定复合物,命名为FcP。共价偶联策略建立了持久的T加权对比能力。随后的透明质酸(HA)功能化赋予HA-FcP系统CD44特异性靶向能力,在载脂蛋白E缺陷模型中,其斑块积累比非靶向对应物高1.7倍。值得注意的是,这种纳米结构能够在注射后120小时内对动脉粥样硬化病变进行连续的MRI可视化。系统的生物安全性评估显示细胞活力>90%,血液学参数正常。这项工作通过二维材料的自旋态操纵开创了MRI造影剂的新范例,为精准心血管诊断提供了一个转化平台。

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