School of Medical Imaging, Xuzhou Medical University, Xuzhou, 221004, People's Republic of China.
Department of Radiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, People's Republic of China.
Int J Nanomedicine. 2022 Nov 17;17:5413-5429. doi: 10.2147/IJN.S371873. eCollection 2022.
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.
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.
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.
The fabricated multimodal imaging nanoparticles with ROS-scavenging ability provided a new avenue for the diagnosis and treatment of AS vulnerable plaques.
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。
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。
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。
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。
