Hybrid, metal oxide-peptide amphiphile micelles for molecular magnetic resonance imaging of atherosclerosis

Abstract

BackgroundAtherosclerosis, a major source of cardiovascular disease, is asymptomatic for decades until the activation of thrombosis and the rupture of enlarged plaques, resulting in acute coronary syndromes and sudden cardiac arrest. Magnetic resonance imaging (MRI) is a noninvasive nuclear imaging technique to assess the degree of atherosclerotic plaque with high spatial resolution and excellent soft tissue contrast. However, MRI lacks sensitivity for preventive medicine, which limits the ability to observe the onset of vulnerable plaques. In this study, we engineered hybrid metal oxide-peptide amphiphile micelles (HMO-Ms) that combine an inorganic, magnetic iron oxide or manganese oxide inner core with organic, fibrin-targeting peptide amphiphiles, consisting of the sequence CREKA, for potential MRI imaging of thrombosis on atherosclerotic plaques.ResultsHybrid metal oxide-peptide amphiphile micelles, consisting of an iron oxide (Fe-Ms) or manganese oxide (Mn-Ms) core with CREKA peptides, were self-assembled into 20–30 nm spherical nanoparticles, as confirmed by dynamic light scattering and transmission electron microscopy. These hybrid nanoparticles were found to be biocompatible with human aortic endothelial cells in vitro, and HMO-Ms bound to human clots three to five times more efficiently than its non-targeted counterparts. Relaxivity studies showed ultra-high r2 value of 457 mM−1 s−1 and r1 value of 0.48 mM−1 s−1 for Fe-Ms and Mn-Ms, respectively. In vitro, MR imaging studies demonstrated the targeting capability of CREKA-functionalized hybrid nanoparticles with twofold enhancement of MR signals.ConclusionThis novel hybrid class of MR agents has potential as a non-invasive imaging method that specifically detects thrombosis during the pathogenesis of atherosclerosis.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0420-8) contains supplementary material, which is available to authorized users.

Collagenase‐Cleavable Peptide Amphiphile Micelles as a Novel Theranostic Strategy in Atherosclerosis

“…To investigate particle circulation and half‐life, MCG PAMs were injected into C57BL/6J mice and blood was collected at 5 min, 1, 3, 8, and 24 h post‐injection before analysis via inductively coupled plasma‐optical emission spectrometry (ICP‐OES, Figures S5 and S6, Supporting Information). The t 1/2α and t 1/2β of MCG PAMs were determined to be 1.3 ± 0.1 and 23.9 ± 1.8 h, respectively, which is consistent with MCP‐1, scrambled MCP‐1, and Gd‐based micelles previously reported and is a marked improvement over commercially available Gd contrast agents that undergo rapid elimination by the kidneys with a terminal plasma half‐life of 15–20 min in murine models …”

Organic and inorganic nanoparticle vaccines for prevention of infectious diseases

“…A wide variety of different organic nanoparticles have been developed as vaccine platform because of their biocompatibility, biodegradability, and general lack of toxicity [13]. Purely organic nanoparticles possess many advantages over other existing nanoparticle platforms, including self-assembly of antigens and adjuvants in physiologically mild conditions, and chemical diversity for accommodating a variety of modalities, compositions, sizes, shapes, and surface functionalization [16,42]. This section will discuss recent developments of organic nanoparticle vaccine delivery platform, including polymeric nanoparticles, liposomes, and virus-like particles (VLPs).…”

“…Most inorganic materials have a smaller particle size, improved stability, controlled tunability, enhanced permeability, high drug loadings, and a triggered release profile, which is ideal for antigen delivery as a vaccine [14,15]. These newer generations are typically constructed with an inorganic core and an organic outer shell to afford hybrid inorganic nanomaterials [16,67]. In this section, we briefly review the recent development of these inorganic nanoparticles in vaccines as both carriers and adjuvants.…”

“…gold nanoparticles, metal oxide, and mesoporous silica nanoparticles) based on the components that construct the structure. Most organic materials are biocompatible, biodegradable, and nontoxic, while most inorganic materials have a smaller particle size, improved stability, controlled tunability, enhanced permeability, high drug loadings, and a triggered release profile [13][14][15][16] (figure 1). In this review, current novel vaccine strategies using nanoparticle are discussed, focusing on recent developments of organic and inorganic nanoparticles for the induction of immune responses against infectious diseases (table 1).…”

Iron Oxide Nanoparticles as Imaging and Therapeutic Agents for Atherosclerosis

“…Although IONPs naturally become internalized by phagocytosing cells, targeting IONP contrast agents to specific markers of plaque components by attaching biological ligands to the surface of the nanoparticle increases localization and is the most common technique utilized to improve IONP specificity at atherosclerotic lesions. [35][36][37][38][39] IONPs are most commonly functionalized with antibodies through covalent bonding reactions directly to reactive surface groups 40,41 or through intermediate functional groups that have been attached prior to antibody conjugation. 42 Several groups have utilized this method with success in increasing T2-weighted MRI at areas of atherosclerotic plaque formation in vivo in mice.…”