A Nano-Emulsion Platform Functionalized with a Fully Human scFv-Fc Antibody for Atheroma Targeting: Towards a Theranostic Approach to Atherosclerosis

Atherosclerosis is at the onset of the cardiovascular diseases that are among the leading causes of death worldwide. Currently, high-risk plaques, also called vulnerable atheromatous plaques, remain often undiagnosed until the occurrence of severe complications, such as stroke or myocardial infarction. Molecular imaging agents that target high-risk atheromatous lesions could greatly improve the diagnosis of atherosclerosis by identifying sites of high disease activity. Moreover, a “theranostic approach” that combines molecular imaging agents (for diagnosis) and therapeutic molecules would be of great value for the local management of atheromatous plaques. The aim of this study was to develop and characterize an innovative theranostic tool for atherosclerosis. We engineered oil-in-water nano-emulsions (NEs) loaded with superparamagnetic iron oxide (SPIO) nanoparticles for magnetic resonance imaging (MRI) purposes. Dynamic MRI showed that NE-SPIO nanoparticles decorated with a polyethylene glycol (PEG) layer reduced their liver uptake and extended their half-life. Next, the NE-SPIO-PEG formulation was functionalized with a fully human scFv-Fc antibody (P3) recognizing galectin 3, an atherosclerosis biomarker. The P3-functionalized formulation targeted atheromatous plaques, as demonstrated in an immunohistochemistry analyses of mouse aorta and human artery sections and in an Apoe−/− mouse model of atherosclerosis. Moreover, the formulation was loaded with SPIO nanoparticles and/or alpha-tocopherol to be used as a theranostic tool for atherosclerosis imaging (SPIO) and for delivery of drugs that reduce oxidation (here, alpha-tocopherol) in atheromatous plaques. This study paves the way to non-invasive targeted imaging of atherosclerosis and synergistic therapeutic applications.

Download Full-text

Synthetic Approaches for 15N‐labeled Hyperpolarized Heterocyclic Molecular Imaging Agents for 15N NMR Signal Amplification By Reversible Exchange in Microtesla Magnetic Fields

Chemistry - A European Journal ◽

10.1002/chem.202100212 ◽

2021 ◽

Author(s):

Nikita V. Chukanov ◽

Roman V. Shchepin ◽

Sameer M. Joshi ◽

Mohammad S. H. Kabir ◽

Oleg G. Salnikov ◽

...

Keyword(s):

Molecular Imaging ◽

Magnetic Fields ◽

Signal Amplification ◽

Imaging Agents ◽

15N Nmr ◽

Molecular Imaging Agents ◽

Synthetic Approaches

Download Full-text

A Systematic Review of Molecular Imaging Agents Targeting Bradykinin B1 and B2 Receptors

Pharmaceuticals ◽

10.3390/ph13080199 ◽

2020 ◽

Vol 13 (8) ◽

pp. 199

Author(s):

Joseph Lau ◽

Julie Rousseau ◽

Daniel Kwon ◽

François Bénard ◽

Kuo-Shyan Lin

Keyword(s):

Molecular Imaging ◽

Smooth Muscle Contraction ◽

Therapeutic Interventions ◽

Imaging Agents ◽

Kinin System ◽

Normal Tissues ◽

Molecular Imaging Agents ◽

Inflammatory State ◽

B2 Receptors ◽

Tissue Trauma

Kinins, bradykinin and kallidin are vasoactive peptides that signal through the bradykinin B1 and B2 receptors (B1R and B2R). B2R is constitutively expressed in healthy tissues and mediates responses such as vasodilation, fluid balance and retention, smooth muscle contraction, and algesia, while B1R is absent in normal tissues and is induced by tissue trauma or inflammation. B2R is activated by kinins, while B1R is activated by kinins that lack the C-terminal arginine residue. Perturbations of the kinin system have been implicated in inflammation, chronic pain, vasculopathy, neuropathy, obesity, diabetes, and cancer. In general, excess activation and signaling of the kinin system lead to a pro-inflammatory state. Depending on the disease context, agonism or antagonism of the bradykinin receptors have been considered as therapeutic options. In this review, we summarize molecular imaging agents targeting these G protein-coupled receptors, including optical and radioactive probes that have been used to interrogate B1R/B2R expression at the cellular and anatomical levels, respectively. Several of these preclinical agents, described herein, have the potential to guide therapeutic interventions for these receptors.

Download Full-text