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Article

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

by 1,†, 2,3,4,†, 2,3,4, 2,3,4, 5, 6, 6, 7,*, 2,3,4 and 1,*
1
Department of Minimally Invasive Interventional Radiology, Guangzhou Panyu Central Hospital, Guangzhou 511400, China
2
MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China
3
Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China
4
Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou 510631, China
5
Neuroscience Laboratory, Hugo Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, USA
6
Institution of Guang Dong Cord Blood Bank, Guangzhou 510700, China
7
Department of Radiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: João Paulo Borges, Lionel Fernel Gamarra, Alexandre Malta Rossi and Javier Bustamante Mamani
Pharmaceutics 2022, 14(5), 1083; https://doi.org/10.3390/pharmaceutics14051083
Received: 5 April 2022 / Revised: 9 May 2022 / Accepted: 16 May 2022 / Published: 18 May 2022
(This article belongs to the Special Issue Magnetic Nanoparticles for Therapy and Diagnosis in Nanomedicine)
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. View Full-Text
Keywords: early atherosclerosis; VCAM-1; MRI; rapamycin; bimodal imaging; Rap/Fe3O4@VHP-Lipo early atherosclerosis; VCAM-1; MRI; rapamycin; bimodal imaging; Rap/Fe3O4@VHP-Lipo
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MDPI and ACS Style

Huang, C.; Huang, W.; Zhang, L.; Zhang, C.; Zhou, C.; Wei, W.; Li, Y.; Zhou, Q.; Chen, W.; Tang, Y. Targeting Peptide, Fluorescent Reagent Modified Magnetic Liposomes Coated with Rapamycin Target Early Atherosclerotic Plaque and Therapy. Pharmaceutics 2022, 14, 1083. https://doi.org/10.3390/pharmaceutics14051083

AMA Style

Huang C, Huang W, Zhang L, Zhang C, Zhou C, Wei W, Li Y, Zhou Q, Chen W, Tang Y. Targeting Peptide, Fluorescent Reagent Modified Magnetic Liposomes Coated with Rapamycin Target Early Atherosclerotic Plaque and Therapy. Pharmaceutics. 2022; 14(5):1083. https://doi.org/10.3390/pharmaceutics14051083

Chicago/Turabian Style

Huang, Chen, Wentao Huang, Lifen Zhang, Chunyu Zhang, Chengqian Zhou, Wei Wei, Yongsheng Li, Quan Zhou, Wenli Chen, and Yukuan Tang. 2022. "Targeting Peptide, Fluorescent Reagent Modified Magnetic Liposomes Coated with Rapamycin Target Early Atherosclerotic Plaque and Therapy" Pharmaceutics 14, no. 5: 1083. https://doi.org/10.3390/pharmaceutics14051083

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