Employment of targeted nanoparticles for imaging of cellular processes in cardiovascular disease

Abstract

Cardiovascular disease (CVD) is a leading cause of global mortality, accounting for pathologies that are primarily of atherosclerotic origin and driven by specific cell populations. A need exists for effective, non-invasive methods to assess the risk of potentially fatal major adverse cardiovascular events (MACE) before occurrence and to monitor post-interventional outcomes such as tissue regeneration. Molecular imaging has widespread applications in CVD diagnostic assessment, through modalities including magnetic resonance imaging (MRI), positron emission tomography (PET), and acoustic imaging methods. However, current gold-standard small molecule contrast agents are not cell-specific, relying on non-specific uptake to facilitate imaging of biologic processes. Nanomaterials can be engineered for targeted delivery to specific cell populations, and several nanomaterial systems have been developed for pre-clinical molecular imaging. Here, we review recent advances in nanoparticle-mediated approaches for imaging of cellular processes in cardiovascular disease, focusing on efforts to detect inflammation, assess lipid accumulation, and monitor tissue regeneration.

Figure 1.

Schematic representation of strategies to utilize nanomaterials for imaging cellular processes in CVD. Assessing inflammation and lipid accumulation, and monitoring tissue regeneration are 3 key areas of recent advances. Specific references for the depicted nanoparticles and targeting strategies are listed in Table 1. HFn = heavy chain ferritin; HDL = high density lipoproteins; OPN = osteopontin; IONP = iron oxide nanoparticle; CPP = cell-penetrating peptide.

Figure 2.

Fe-doped hollow silica nanospheres conjugated with anti-CD68 antibody for macrophage burden detection in atherosclerotic plaques via US and MRI. a) Schematic and transmission electron microscopy (TEM) of CD68-targeting, Fe-doped hollow silica nanospheres (CD68-Fe-HSNs) in macrophages. b) Illustration and images of CD8-Fe-HSN uptake by plaque macrophages and detection via contrast-enhanced ultrasound (CEUS), MRI, TEM, and immunofluorescence.

Figure 3.

Semiconducting polymer (SP) based photoacoustic nanoparticles (PANP) for labeling and tracking of human embryonic stem cell-derived cardiomyocytes (hESC-CMs). a) Structure and b) TEM of SP PANPs. c) Brightfield microscopy of a sectioned slide of the heart to investigate hESC-Cm engraftment. d) PAI detection of engrafted hESC-CMs (red) in a fixed mouse heart. e) Detection of engrafted hESC-CMs (blue) in host myocardium via fluorescence imaging using intrinsic fluorescence of PANPs. f) Confocal microscopy of engrafted hESC-CMs within host myocardium. Both DAPI (blue) and cardiac troponin T (cTnT) (green) indicate host and engrafted cardiomyocytes. The engrafted hESC-CMs are distinguished via staining with human mitochondria antibody (purple) and via PANP fluorescence (red).