Huang Chen, Huang Wentao, Zhang Lifen, Zhang Chunyu, Zhou Chengqian, Wei Wei, Li Yongsheng, Zhou Quan, Chen Wenli, Tang Yukuan
Department of Minimally Invasive Interventional Radiology, Guangzhou Panyu Central Hospital, Guangzhou 511400, China.
MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China.
Pharmaceutics. 2022 May 18;14(5):1083. doi: 10.3390/pharmaceutics14051083.
Atherosclerosis is the leading cause of global morbidity and mortality. Its therapy requires research in several areas, such as diagnosis of early arteriosclerosis, improvement of the pharmacokinetics and bioavailability of rapamycin as its therapeutic agents. Here, we used the targeting peptide VHPKQHR (VHP) (or fluorescent reagent) to modify the phospholipid molecules to target vascular cell adhesion molecule-1 (VCAM-1) and loaded ultrasmall paramagnetic iron oxide (USPIO/FeO) plus rapamycin (Rap) to Rap/FeO@VHP-Lipo (VHPKQHR-modified magnetic liposomes coated with Rap). This nanoparticle can be used for both the diagnosis and therapy of early atherosclerosis. We designed both an ex vivo system with mouse aortic endothelial cells (MAECs) and an in vivo system with ApoE knockout mice to test the labeling and delivering potential of Rap/FeO@VHP-Lipo with fluorescent microscopy, flow cytometry and MRI. Our results of MRI imaging and fluorescence imaging showed that the T2 relaxation time of the Rap/FeO@VHP-Lipo group was reduced by 2.7 times and 1.5 times, and the fluorescence intensity increased by 3.4 times and 2.5 times, respectively, compared with the normal saline group and the control liposome treatment group. It showed that Rap/FeO@VHP-Lipo realized the diagnosis of early AS. Additionally, our results showed that, compared with the normal saline and control liposomes treatment group, the aortic fluorescence intensity of the Rap/FeO@VHP-Lipo treatment group was significantly weaker, and the T2 relaxation time was prolonged by 8.9 times and 2.0 times, indicating that the targeted diagnostic agent detected the least plaques in the Rap/FeO@VHP-Lipo treatment group. Based on our results, the synthesized theragnostic Rap/FeO@VHP-Lipo serves as a great label for both MRI and fluorescence bimodal imaging of atherosclerosis. It also has therapeutic effects for the early treatment of atherosclerosis, and it has great potential for early diagnosis and can achieve the same level of therapy with a lower dose of Rap.
动脉粥样硬化是全球发病和死亡的主要原因。其治疗需要在多个领域进行研究，如早期动脉硬化的诊断、作为治疗药物的雷帕霉素的药代动力学和生物利用度的改善。在此，我们使用靶向肽VHPKQHR（VHP）（或荧光试剂）修饰磷脂分子以靶向血管细胞黏附分子-1（VCAM-1），并将超小顺磁性氧化铁（USPIO/FeO）加雷帕霉素（Rap）负载到Rap/FeO@VHP-Lipo（涂有Rap的VHPKQHR修饰磁性脂质体）中。这种纳米颗粒可用于早期动脉粥样硬化的诊断和治疗。我们设计了一个含有小鼠主动脉内皮细胞（MAECs）的体外系统和一个含有载脂蛋白E基因敲除小鼠的体内系统，以通过荧光显微镜、流式细胞术和磁共振成像测试Rap/FeO@VHP-Lipo的标记和递送潜力。我们的磁共振成像和荧光成像结果表明，与生理盐水组和对照脂质体治疗组相比，Rap/FeO@VHP-Lipo组的T2弛豫时间分别降低了2.7倍和1.5倍，荧光强度分别增加了3.4倍和2.5倍。这表明Rap/FeO@VHP-Lipo实现了早期动脉粥样硬化的诊断。此外，我们的结果表明，与生理盐水和对照脂质体治疗组相比，Rap/FeO@VHP-Lipo治疗组的主动脉荧光强度明显较弱，T2弛豫时间延长了8.9倍和2.0倍，表明靶向诊断剂在Rap/FeO@VHP-Lipo治疗组中检测到的斑块最少。基于我们的结果，合成的诊疗一体化Rap/FeO@VHP-Lipo是动脉粥样硬化磁共振成像和荧光双模态成像的良好标记物。它对动脉粥样硬化的早期治疗也有治疗作用，具有早期诊断的巨大潜力，并且可以用较低剂量的Rap达到相同的治疗水平。
