Research Article Targeting Nanostrategies for Imaging of Atherosclerosis Angela Costagliola di Polidoro , 1,2 Agnese Grassia, 1,2 Francesca De Sarno, 1,2 Paolo Bevilacqua, 3 Valentina Mollo, 2 Eugenia Romano, 1,2 Maria Donata Di Taranto , 4,5 Giuliana Fortunato, 4,5 Umberto Marcello Bracale , 6 Liberatore Tramontano, 3 Tommaso Claudio Diomaiuti, 3 and Enza Torino 1,2,7 1 DepartmentofChemical,MaterialsEngineering&IndustrialProduction,UniversityofNaplesFedericoII,PiazzaleTecchio80, Naples 80125, Italy 2 Center for Advanced Biomaterials for Health Care (CABHC), Fondazione Istituto Italiano di Tecnologia (IIT)@CRIB, Largo Barsanti e Matteucci 53, Naples 80125, Italy 3 IRCCS SDN, via Gianturco 113, Naples, Italy 4 Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, via S. Pansini 5, Naples 80131, Italy 5 CEINGE Advanced Biotechnologies S.C. A R.L., via Gaetano Salvatore 486, Naples 80145, Italy 6 Department of Public Health, University of Naples Federico II, via S. Pansini 5, Naples 80131, Italy 7 Interdisciplinary Research Center on Biomaterials (CRIB), Piazzale Tecchio 80, Naples 80125, Italy Correspondence should be addressed to Enza Torino; enza.torino@unina.it Received 28 October 2020; Revised 2 March 2021; Accepted 16 March 2021; Published 1 April 2021 Academic Editor: Alexander R. Haug Copyright © 2021 Angela Costagliola di Polidoro et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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 to- mography (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. 1. Introduction To date, Atherosclerotic Cardiovascular Disease (ASCVD) represents one of the leading causes of death daily world- wide. However, it is characterized by an increasing incidence that is difficult to determine accurately since ASCVD is a predominantly asymptomatic condition [1]. Atherosclerosis is an inflammatory pathology that affects the intima and media layers of arteries of medium and large size and is characterized by the formation of typical Ath- erosclerotic lipid Plaques (AP) that cause the narrowing of the vessel lumen. During atherogenesis, the process of AP formation, specific changes occur in the endothelial lining of the vessel allowing the invasion by inflammatory and Hindawi Contrast Media & Molecular Imaging Volume 2021, Article ID 6664471, 10 pages https://doi.org/10.1155/2021/6664471