Targeting Nanostrategies for Imaging of Atherosclerosis

Angela Costagliola Di Polidoro,Agnese Grassia,Maria Donata Di Taranto,Enza Torino,Liberatore Tramontano,Paolo Bevilacqua,Umberto Marcello Bracale,Eugenia Romano,Valentina Mollo,Francesca De Sarno,Tommaso Claudio Diomaiuti,Giuliana Fortunato,Alexander R Haug

doi:10.1155/2021/6664471

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.

Highlights

To date, Atherosclerotic Cardiovascular Disease (ASCVD) represents one of the leading causes of death daily worldwide
We explored the ability of anti-CD36 decorated crosslinked Hyaluronic Acid Nanoparticles (Ab36-cHANPs) encapsulating Gd-DTPA to preserve the property of Hydrodenticity in a complex environment such as the human Atherosclerotic lipid Plaques (AP) removed by surgical endarterectomy. e surface functionalization with the antibody anti-CD36 in combination with the double function of hyaluronic acid (HA) as hydrophilic polymer boosting Gd-DTPA relaxivity by Hydrodenticity and intrinsic target of the AP confer to the formulation a great potential for the active targeting and boosted Magnetic Resonance Imaging (MRI) of atherosclerosis
An X-junction chip is used to implement a hydrodynamic flow focusing regime, and nanoparticles are produced by nanoprecipitation. e solvent phase of HA and Gd-DTPA is injected in the middle channel and the nonsolvent phase of acetone and DVS in the side channels. cHANPs have a mean size of 210 ± 65 nm as shown by particle size distribution (PSD) reported in Figure 1(a)

Summary

Introduction

Atherosclerotic Cardiovascular Disease (ASCVD) represents one of the leading causes of death daily worldwide. 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 Atherosclerotic lipid Plaques (AP) that cause the narrowing of the vessel lumen. The degree of stenosis of the vessel is only partially related to the risks associated with this pathology, with the AP composition being the main cause of instability phenomena that lead to the manifestation of clinical symptoms such as stroke, heart attack, and ischemia [6]. The stability of APs is influenced by many factors, such as the lipid core, the thickness of the fibrous cap, and the inflammation within the cap. e rupture is most likely associated with “vulnerable plaques” and may cause acute clinical events (e.g., stroke and heart attack) and thrombosis [7,8,9]

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