Targeting Peptide, Fluorescent Reagent Modified Magnetic Liposomes Coated with Rapamycin Target Early Atherosclerotic Plaque and Therapy

被引:17
作者
Huang, Chen [1 ]
Huang, Wentao [2 ,3 ,4 ]
Zhang, Lifen [2 ,3 ,4 ]
Zhang, Chunyu [2 ,3 ,4 ]
Zhou, Chengqian [5 ]
Wei, Wei [6 ]
Li, Yongsheng [6 ]
Zhou, Quan [7 ]
Chen, Wenli [2 ,3 ,4 ]
Tang, Yukuan [1 ]
机构
[1] Guangzhou Panyu Cent Hosp, Dept Minimally Invas Intervent Radiol, Guangzhou 511400, Peoples R China
[2] South China Normal Univ, Coll Biophoton, MOE Key Lab Laser Life Sci Inst Laser Life Sci, Guangzhou 510631, Peoples R China
[3] South China Normal Univ, Coll Biophoton, Guangdong Prov Key Lab Laser Life Sci, Guangzhou 510631, Peoples R China
[4] South China Normal Univ, Inst Brain Res & Rehabil, Guangzhou 510631, Peoples R China
[5] Hugo Moser Res Inst, Neurosci Lab, Baltimore, MD 21205 USA
[6] Inst Guang Dong Cord Blood Bank, Guangzhou 510700, Peoples R China
[7] Southern Med Univ, Dept Radiol, Affiliated Hosp 3, Guangzhou 510630, Peoples R China
基金
中国国家自然科学基金;
关键词
early atherosclerosis; VCAM-1; MRI; rapamycin; bimodal imaging; Rap; Fe3O4@VHP-Lipo; INDUCED VCAM-1 EXPRESSION; CELL-ADHESION MOLECULE-1; ALPHA-INDUCED VCAM-1; SENSITIVE LIPOSOMES; DELIVERY; NANOPARTICLES; MACROPHAGE; PATTERNS;
D O I
10.3390/pharmaceutics14051083
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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/Fe3O4) plus rapamycin (Rap) to Rap/Fe3O4@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/Fe3O4@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/Fe3O4@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/Fe3O4@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/Fe3O4@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/Fe3O4@VHP-Lipo treatment group. Based on our results, the synthesized theragnostic Rap/Fe3O4@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.
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页数:24
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