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.