Construction of dual nanomedicines for the imaging and alleviation of atherosclerosis

Abstract

Magnetic resonance imaging (MRI) is an essential tool for the diagnosis of atherosclerosis, a chronic cardiovascular disease. MRI primarily uses superparamagnetic iron oxide (SPIO) as a contrast agent. However, SPIO integrated with therapeutic drugs has rarely been studied. In this study, we explored biocompatible paramagnetic iron-oxide nanoparticles (NPs) in a complex with low pH-sensitive cyclodextrin for the diagnostic imaging and treatment of atherosclerosis. The NPs were conjugated with profilin-1 antibody (PFN1) to specifically target vascular smooth muscle cells (VSMCs) in the atherosclerotic plaque and integrated with the anti-inflammatory drug, rapamycin. The PFN1-CD-MNPs were easily binded to the VSMCs, indicating their good biocompatibility and low renal toxicity over the long term. Ex vivo near-infrared fluorescence (NIRF) imaging and in vivo MRI indicated the accumulation of PFN1-CD-MNPs in the atherosclerotic plaque. The RAP@PFN1-CD-MNPs alleviated the progression of arteriosclerosis. Thus, PFN1-CD-MNPs served not only as multifunctional imaging probes but also as nanovehicles for the treatment of atherosclerosis.

Small Dimension—Big Impact! Nanoparticle-Enhanced Non-Invasive and Intravascular Molecular Imaging of Atherosclerosis In Vivo

“…Furthermore, PFN1-CD-MNPs were loaded with rapamycin via cyclodextrin (Rap@PFN1-CD-MNP) and administered every three days intraperitoneally to ApoE-deficient mice after two months of a high-fat diet for a time period of another two months. Compared to a saline control group, the untargeted therapeutic nanoparticle, Rap@PFN1-CD-MNP, seemed to reduce plaque burden as assessed by histology and ex vivo fluorescence imaging, combined with less toxicity as indicated by blood biochemistry analysis [23].…”

Nanotechnology for Molecular Imaging of Atherosclerosis: Current Design and Approaches

“…The ideal NIR imaging best work in the NIR spectrum (600-900 nm) due to a minimal interference of the fluorescence, a sensitive and non-invasive effect of imaging, and an improved tissue depth penetration [70,72]. The success of functionalized MRI-NIRF imaging was obtained by the conjugation of profilin-1 antibodies with β-cyclodextrin magnetic nanoparticles (PFN1-CD-MNPs) loaded NIRF cyanine dye, that showed significantly high fluorescence signals in the aorta, leading to better atherosclerotic plaque targeted-imaging [73]. Another research on MRI-NIRF imaging of versatile ultra-small super-paramagnetic iron oxide (VUSPIO) similarly demonstrated excellent fluorescence signal in the plaque site, indicating potential of functional VUSPIO as a biocompatible and atheroma-specific diagnostic agent [85].…”

“…There are several NIRF dyes used for diagnosing and imaging atherosclerotic plaque known as cyanines. They are considered as preferable candidates due to improve physical properties and greatscale synthesis availability, whilst the most prominent of all is the indocyanine green (ICG) [74,[76][77][78]86].…”

Theranostic nanoplatform to target macrophages enables the inhibition of atherosclerosis progression and fluorescence imaging of plaque in ApoE(−/−) mice

“…Because the proliferation and migration of vascular smooth muscle cells (VSMCs) present in AS lesions is related to the formation of fibrous cap, profilin-1 highly expressed on the surface of VSMCs was also chosen as the target [ 15 ]. Zhang SH et al covalently combined Profilin-1 Antibody (PFN1) with paramagnetic Fe 3 O 4 to obtain near-infrared fluorescence imaging/MRI nanoprobe, which could locate AS plaques by imaging and moderate the progression of AS [ 16 ]. In the early stage of AS, neutrophils appear in the lesions of AS, which was used as molecular targets for the ultra-early diagnosis of AS.…”