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

Abstract

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.

Advances in Atherosclerosis Theranostics Harnessing Iron Oxide‐Based Nanoparticles

“…This outcome was attributed to the enhanced stability and bioavailability of rapamycin facilitated by the nano‐drug delivery system (Figure 4h,i ). [ 68 ]…”

“…i) MRI T2 mapping sequence imaging to detect the treatment effect of mice in three different groups with different treatments for 2 months. Reproduced under terms of the CC-BY license [68]. Copyright 2022, The Authors, Published by MDPI, Basel, Switzerland.…”

Natural compounds from botanical drugs targeting mTOR signaling pathway as promising therapeutics for atherosclerosis: A review

“…Rapamycin is an inhibitor of the mTOR signaling pathway. By applying advanced technology that makes Rapamycin target atherosclerotic plaques in experimental animals, a reduction in inflammation and lipid load and a shrinking of plaques was also observed in animal models, further suggesting that reduced mTOR signaling pathway activity can promote atheroprotective changes in AS (Huang et al, 2022a;Cheraga et al, 2022;Guo et al, 2022).…”

Magnetic Nanoparticles for Therapy and Diagnosis in Nanomedicine

“…Of the papers presented in this Special Issue, five papers studied therapies [ 1 , 2 , 3 , 4 , 5 ], three papers aimed at diagnosis [ 6 , 7 , 8 ], two papers focused on the theranostic process [ 9 , 10 ], and two review articles evaluated the theranostic potential of MNPs in medical applications [ 11 , 12 ].…”

“…In the work of Li et al [ 9 ] and Huang et al [ 10 ], MNPs were addressed with a view to theranostic applications. Thus, Li et al developed a polydopamine-based nanocarrier modified with MNPs and Pt nanoparticles loaded with necrostatin-1 (Nec-1), showing the great potential of this nanomaterial for the bimodal imaging and therapy of lupus nephritis.…”