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Targeting Nanostrategies for Imaging of Atherosclerosis
Angela Costagliola di Polidoro1,2, Agnese Grassia1,2, Francesca De Sarno1,2
1Department of Chemical, Materials Engineering & Industrial Production, University of Naples Federico II, Piazzale Tecchio 80, Naples 80125, Italy.
Insights
Researchers developed targeted hydrogel nanoparticles to improve atherosclerotic plaque imaging. These nanoparticles enhance magnetic resonance imaging contrast, potentially enabling earlier diagnosis of vulnerable plaques and reducing cardiovascular events.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cardiovascular Imaging
Background:
- Atherosclerosis remains a leading global cause of death, with current diagnostic methods like CT and X-ray angiography struggling to identify high-risk plaques.
- Magnetic resonance imaging (MRI) offers high spatial resolution for characterizing atherosclerotic plaque (AP) anatomy and composition, crucial for detecting vulnerable plaques.
- Hydrogel matrices enhance Gadolinium-based contrast agents (CAs) via Hydrodenticity, improving MRI performance and reducing toxicity for atherosclerotic cardiovascular disease (ASCVD) imaging.
Purpose of the Study:
- To evaluate crosslinked Hyaluronic Acid Nanoparticles (cHANPs) for enhanced MRI contrast in atherosclerotic plaques.
- To assess the efficacy of antibody-decorated cHANPs (Ab36-cHANPs) for active targeting of AP-associated macrophages.
- To investigate the potential of these targeted nanoparticles for earlier and more accurate ASCVD diagnosis.
Main Methods:
- Development of crosslinked Hyaluronic Acid Nanoparticles (cHANPs) encapsulating Gd-DTPA.
- Surface decoration of cHANPs with anti-CD36 antibodies (Ab36-cHANPs) for targeted macrophage interaction.
- Testing of cHANPs and Ab36-cHANPs in the complex environment of human atherosclerotic plaques.
Main Results:
- Hydrodenticity of cHANPs and Ab36-cHANPs was confirmed to be preserved within the complex atherosclerotic plaque environment.
- Preliminary results indicate interaction of these targeted nanoparticles with the atherosclerotic plaque.
- The study demonstrates the potential of these nanoparticles to improve MRI-based detection of vulnerable atherosclerotic plaques.
Conclusions:
- Crosslinked Hyaluronic Acid Nanoparticles (cHANPs) show promise for enhancing MRI contrast in atherosclerotic plaques.
- Antibody-decorated cHANPs (Ab36-cHANPs) demonstrate targeted interaction, suggesting potential for specific AP imaging.
- These findings support the development of advanced nanoparticle-based imaging agents for improved cardiovascular disease diagnosis and risk stratification.
Abstract:
Despite the progress in cardiovascular research, atherosclerosis still represents the main cause of death worldwide. Clinically, the diagnosis of Atherosclerotic Cardiovascular Disease (ASCVD) relies on imaging methodologies including X-ray angiography and computed tomography (CT), which however still fails in the identification of patients at high risk of plaque rupture, the main cause of severe clinical events as stroke and heart attack. Magnetic resonance imaging, which is characterized by very high spatial resolution, could provide a better characterization of atherosclerotic plaque (AP) anatomy and composition, aiding in the identification of "vulnerable" plaques. In this context, hydrogel matrices, which have been demonstrated able to boost relaxometric properties of Gd-based contrast agents (CAs) by the effect of Hydrodenticity, represent a valuable tool towards the precision imaging of ASCVD improving the performance of this class of CAs while reducing systemic toxicity. In particular, hydrogel nanoparticles encapsulating Gd-DTPA can further contribute to providing CA-specific accumulation in the AP by nanoparticle surface decoration triggering an active targeting of the AP with the overall effect of allowing an earlier and more accurate diagnosis. In this work, we tested crosslinked Hyaluronic Acid Nanoparticles (cHANPs) in the complex environment of human atherosclerotic plaque. In addition, the surface of cHANPs was decorated with the antibody anti-CD36 (Ab36-cHANPs) for the active targeting of AP-associated macrophages. Results demonstrate that the Hydrodenticity of cHANPs and Ab36-cHANPs is preserved in this complex system and, preliminarily, that interaction of these probes with the AP is present.
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