通过 ROS 清除纳米颗粒的动脉粥样硬化易损斑块的靶向治疗及 MR/荧光双模式成像示踪。

PURPOSE: Early diagnosis and treatment of atherosclerosis (AS) vulnerable plaque has important clinical significance for the prognosis of patients. In this work, the integrated diagnosis and treatment nanoparticles based on Gd-doped Prussian blue (GPB) were constructed for the fluorescence/MR dual-mode imaging and anti-ROS treatment of vulnerable AS plaques in vitro and in vivo. METHODS: To fabricate the theranostic NPs, GPB was modified with water-soluble polymer polyethyleneimine (PEI), fluorescence molecule rhodamine (Rd), and targeted molecule dextran sulfate (DS) step by step via electrostatic adsorption to construct GPRD NPs. The fluorescence/MR imaging ability and various nano-enzymes activity of GPRD NPs were detected, and the biocompatibility and safety of GPRD were also evaluated. Subsequently, RAW264.7 cells and ApoE -/- model mice were used to evaluate the effect of GPRD NPs on the targeted dual-mode imaging and anti-ROS treatment of vulnerable plaque in vitro and in vivo. RESULTS: The experimental results showed that our fabricated GPRD NPs not only displayed excellent MR/fluorescence dual-modality imaging of vulnerable plaque in vivo but also effectively utilized the nano-enzyme activity of GPB to inhibit the AS progress by ROS scavenging and the following reduction of inflammation, apoptosis, and foam cells' formation, providing a new avenue for the diagnosis and treatment of AS vulnerable plaque. CONCLUSION: The fabricated multimodal imaging nanoparticles with ROS-scavenging ability provided a new avenue for the diagnosis and treatment of AS vulnerable plaques.

目的：动脉粥样硬化（AS）易损斑块的早期诊断和治疗对患者的预后具有重要的临床意义。在这项工作中，构建了基于掺镝普鲁士蓝（GPB）的集成诊断和治疗纳米粒子，用于体外和体内易损 AS 斑块的荧光/MR 双模成像和抗 ROS 治疗。

方法：为了制备治疗性纳米粒子，GPB 通过静电吸附逐步用水溶性聚合物聚乙烯亚胺（PEI）、荧光分子罗丹明（Rd）和靶向分子硫酸葡聚糖（DS）进行修饰，以构建 GPRD 纳米粒子。检测了 GPRD 纳米粒子的荧光/MR 成像能力和各种纳米酶活性，并评价了 GPRD 的生物相容性和安全性。随后，使用 RAW264.7 细胞和 ApoE -/- 模型小鼠，评估 GPRD 纳米粒子对易损斑块的靶向双模式成像和体内外抗 ROS 治疗的效果。

结果：实验结果表明，我们制备的 GPRD 纳米粒子不仅显示了易损斑块在体内的优异 MR/荧光双模成像，而且还通过清除 ROS 有效利用了 GPB 的纳米酶活性，从而减少炎症、细胞凋亡和泡沫细胞的形成，抑制 AS 的进展，为 AS 易损斑块的诊断和治疗提供了新途径。

结论：具有 ROS 清除能力的构建的多模态成像纳米粒子为 AS 易损斑块的诊断和治疗提供了新途径。