Li Danyan, Chang Pengzhao, Bian Shuang, Li Bangbang, Zhu Yangang, Wang Yanchen, Hou Pingfu, Li Jingjing
School of Medical Imaging, Xuzhou Medical University, Xuzhou 221004, China.
Department of Radiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, China.
Biomater Res. 2025 May 9;29:0204. doi: 10.34133/bmr.0204. eCollection 2025.
The major fatal factor of cardiovascular disease is atherosclerosis, which is a chronic inflammatory disease featured by immune cell infiltration within arterial plaques. Dendritic cells (DCs) are central stimulators of atherosclerotic inflammation, with mature DCs generating pro-inflammatory signals within plaque lesions and tolerogenic DCs promoting anti-inflammatory cytokine production and regulatory T cell (T) activation. In this work, spontaneous induced cascade targeting biomimetic nanoparticles (MM@HGPBRD) were constructed to target DCs in atherosclerosis plaques to inhibit DC maturation. In vitro and in vivo experiment results showed that the MM@HGPBRD effectively slowed atherosclerosis progression by the synergistic effect of multiple components. The coating macrophage membrane helped the nanoparticles to evade immune clearance and home to the atherosclerotic site. Then, the nanozyme activity of hollow mesoporous Prussian blue (HGPB) produced oxygen to break the membrane and expose DC-SIGN aptamer to realize cascade targeting to DCs and enhance the targeted release of rapamycin (RAPA) to inhibit DC maturation. The whole process regulated the inflammatory and immune microenvironment of atherosclerosis. At the same time, the excellent magnetic resonance imaging (MRI) ability of HGPB favored the MRI of DCs in atherosclerosis plaque. This study provides new avenue for spontaneous induced cascade targeting and modulating DC maturation to improve atherosclerosis inflammation and immune microenvironment.
心血管疾病的主要致死因素是动脉粥样硬化，这是一种慢性炎症性疾病，其特征是动脉斑块内有免疫细胞浸润。树突状细胞（DCs）是动脉粥样硬化炎症的核心刺激因子，成熟的DCs在斑块病变内产生促炎信号，而耐受性DCs则促进抗炎细胞因子的产生和调节性T细胞（T）的激活。在这项工作中，构建了自发诱导级联靶向仿生纳米颗粒（MM@HGPBRD），以靶向动脉粥样硬化斑块中的DCs，抑制DCs成熟。体外和体内实验结果表明，MM@HGPBRD通过多种成分的协同作用有效地减缓了动脉粥样硬化的进展。包覆的巨噬细胞膜帮助纳米颗粒逃避免疫清除并归巢到动脉粥样硬化部位。然后，中空介孔普鲁士蓝（HGPB）的纳米酶活性产生氧气以破坏膜并暴露DC-SIGN适配体，从而实现对DCs的级联靶向并增强雷帕霉素（RAPA）的靶向释放以抑制DCs成熟。整个过程调节了动脉粥样硬化的炎症和免疫微环境。同时，HGPB出色的磁共振成像（MRI）能力有利于对动脉粥样硬化斑块中的DCs进行MRI成像。这项研究为自发诱导级联靶向和调节DCs成熟以改善动脉粥样硬化炎症和免疫微环境提供了新途径。
