Cheng Jianing, Hao Liguo, Zhu Xiaorong, Ma Ruifan, Li Silong, Yin Qiangqiang, Wang Dongxu, Hu Haifeng, Zhang Tianyu, Li Zheng, Cong Houyi, Zheng Xiaoyang, He Jun, Wang Yuguang
Department of Molecular Imagine, School of Medical Technology, Qiqihar Medical University, Qiqihar, China.
Department of Image Center, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, China.
J Biomed Mater Res A. 2025 Jan;113(1):e37847. doi: 10.1002/jbm.a.37847.
Triggered by the vulnerability to atherosclerotic plaques, cardiovascular diseases (CVDs) have become a main reason for high mortality worldwide. Thus, there is an urgent need to develop functional molecular imaging modalities to improve the detection rate of vulnerable plaques. In this study, polyethyleneimine (PEI) was coated on the surface of mesoporous silica nanoprobes (MSN) loaded with GdO (MSN@GdO), followed by coupling the fluorescent dye carboxylated heptamethine cyanine (IR808), and then the dextran sulfate (DS) was modified on the surface of MSN@GdO@IR808 by electrostatic adsorption, to construct a targeted and pH-responsive magnetic resonance (MR)/near-infrared fluorescence imaging (NIRF) dual-modal nanoprobe (MSN@GdO@IR808@DS nanoparticles). The nanoprobe presented a more concentrated distribution of spherical shapes in transmission electron microscopy. In vitro simulated vulnerable plaque microenvironment (pH = 5.5) presented significant T-weighted imaging (TWI) signal and longitudinal relaxation in the nanoprobe. Immunofluorescence staining and cellular uptake assays showed that MSN@GdO@IR808@DS nanoparticles have the ability to specially bind to scavenger receptors A (SR-A). In vascular endothelium from the high-fat diet (HFD) New Zealand White rabbits, MSN@GdO@IR808@DS nanoparticles can exhibit specific contrast-enhanced signals by MR/NIRF dual-modal imaging. In addition, cytotoxicity assays and hematoxylin and eosin (H&E) staining results demonstrated that MSN@GdO@IR808@DS nanoparticles have good biocompatibility. Hence, this multifunctional MR/NIRF bimodal nanoprobe provides new experimental and technological ideas for the accurate diagnosis of vulnerable plaques.
受动脉粥样硬化斑块易损性的触发，心血管疾病（CVDs）已成为全球高死亡率的主要原因。因此，迫切需要开发功能性分子成像模式以提高易损斑块的检测率。在本研究中，将聚乙烯亚胺（PEI）包覆在负载GdO的介孔二氧化硅纳米探针（MSN）表面（MSN@GdO），随后偶联荧光染料羧化七甲川花菁（IR808），然后通过静电吸附在MSN@GdO@IR808表面修饰硫酸葡聚糖（DS），构建靶向且pH响应的磁共振（MR）/近红外荧光成像（NIRF）双模态纳米探针（MSN@GdO@IR808@DS纳米颗粒）。该纳米探针在透射电子显微镜下呈现出更集中的球形分布。体外模拟易损斑块微环境（pH = 5.5）在纳米探针中呈现出显著的T加权成像（TWI）信号和纵向弛豫。免疫荧光染色和细胞摄取试验表明，MSN@GdO@IR808@DS纳米颗粒具有与清道夫受体A（SR-A）特异性结合的能力。在高脂饮食（HFD）新西兰白兔的血管内皮中，MSN@GdO@IR808@DS纳米颗粒可通过MR/NIRF双模态成像表现出特异性的对比增强信号。此外，细胞毒性试验和苏木精-伊红（H&E）染色结果表明，MSN@GdO@IR808@DS纳米颗粒具有良好的生物相容性。因此，这种多功能MR/NIRF双模态纳米探针为易损斑块的准确诊断提供了新的实验和技术思路。
