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

Abstract

Extensive translational research has provided considerable progress regarding the understanding of atherosclerosis pathophysiology over the last decades. In contrast, implementation of molecular in vivo imaging remains highly limited. In that context, nanoparticles represent a useful tool. Their variable shape and composition assure biocompatibility and stability within the environment of intended use, while the possibility of conjugating different ligands as well as contrast dyes enable targeting of moieties of interest on a molecular level and visualization throughout various imaging modalities. These characteristics have been exploited by a number of preclinical research approaches aimed at advancing understanding of vascular atherosclerotic disease, in order to improve identification of high-risk lesions prior to oftentimes fatal thromboembolic events. Furthermore, the combination of these targeted nanoparticles with therapeutic agents offers the potential of site-targeted drug delivery with minimized systemic secondary effects. This review gives an overview of different groups of targeted nanoparticles, designed for in vivo molecular imaging of atherosclerosis as well as an outlook on potential combined diagnostic and therapeutic applications.

Keywords: atherosclerosis; molecular imaging; nanoparticles.

Figure 1

Take-home figure. Molecular targets on different stages of atherogenesis: (VINP-28-MNP) VCAM-1-targeting magneto-fluorescent NP [14] (VCAM-TMV) VCAM-1-targeting modified tobacco mosaic virus [15] (anti-ICAM-1-ELIP) ICAM-1-targeting echogenic liposomes [49] (⁶⁴CU-TNP) paramagnetic, positron-emitting, fluorescent targeted iron oxide NP [17] (HDL-like NP) HDL-like multimodality NP [20] (CLIO-Cyam7) crosslinked iron oxide, derivatised with Cyam7 for near infrared fluorescence imaging [47] (gold NP) CD163-targeting gold NP [18] (PFN1-CD-MNP) profilin-1-targeting magneto-fluorescent nanoparticle [23] (αvβ3-integrin-targeting lipid NP) micellar nanoparticle bearing gadolinium and a peptidomimetic RGD-sequence binding αvβ3-integrin [27] (LOX1-NP) liposomal NP coupled with an anti-LOX-1-antibody, containing a fluorescent dye and either gadolinium or indium 111 [32] (oxLDL-targeting USPIO) ultrasmall superparamagnetic iron oxide NP conjugated to anti-mouse oxLDL-antibodies [33] (⁶⁸Ga-NRM-TZ + Ab-TCO) paramagnetic, positron-emitting nano-radiomaterial connected via tetrazine ligation to antibody against oxidized phospholipids [34] (THI0567-lipid NP) liposomal NP bearing gadolinium, selective integrin α4β1 antagonist THI0567 and rhodamine [28] (NAP9-lipid NP) paramagnetic micellar NP conjugated with gadolinium, rhodamine and EMMPRIN-specific binding peptide NAP9 [30] (A5-mNP) micellar NP bearing Cy5.5 and rhodamine, gadolinium and polymers, covalently coupled to phosphatidylserine ligand annexin A5 [36] (⁶⁴Cu-CANF-comb) NPR-C-targeting polymeric positron-emitting nanoparticle (TAP-SiO2@AuNP) gold NP coated with silicon dioxide linked to a thrombin-activatable fluorescent peptide [39] (DDNP) NP based on paramagnetic iron oxide and Indian ink linked to cRGD- and GA-EWVDV-ligands targeting glycoprotein IIb/IIIa and P-selectin on activated platelets [40].