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

Abstract

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.

Self-Similar Functional Circuit Models of Arteries and Deterministic Fractal Operators: Theoretical Revelation for Biomimetic Materials

“…Atherosclerosis is one of the most common cardiovascular diseases and has been extensively studied by epidemiologists [ 4 , 5 ]. High-risk vascular plaque (or vulnerable atheromatous plaque) is the focused object for medical detection and treatment among atherosclerotic diseases [ 6 ]. The dynamic reason for plaque formation is that long-term hypertension in the artery leads to decreased compliance of vascular fiber and eventual hardening.…”

Iron Oxide Nanoparticles in Regenerative Medicine and Tissue Engineering

“…Another theranostic strategy for vulnerable plaques using an adaptable nanoparticle platform was demonstrated in the work of Bonnet [ 198 ]. They developed a PEG-coated nanoemulsion (NE) functionalized with human scFv-Fc antibody and loaded with IONPs and an active pharmaceutical ingredient (alpha-tocopherol).…”

Biodegradable Amphoteric Surfactants in Titration-Ultrasound Formulation of Oil-in-Water Nanoemulsions: Rational Design, Development, and Kinetic Stability

“…The droplet size and polydispersity are crucial factors to identify the type of the obtained formulation as well as to understand its behavior. Furthermore, in addition to composition, the final application (cosmetic, pharmaceutical, or biomedical) of the designed system is also influenced by the droplet size and size distribution [1,4,6]. From Table 1, it can be seen that formulations with a lower concentration of the components, i.e., surfactant and oil phases, revealed the smallest NE droplets (D H , 65-78 nm and PdI < 0.3 for 1% S/0.5% O composition).…”

“…Over recent years, the application of various colloidal formulations (i.e., liposomes, solid lipid nanoparticles, micelles, nanoemulsions, nanocapsules, or nanospheres) has attracted considerable interest in the field of nanomedicine, drug delivery, as well as pharmaceutical and cosmeceutical technology [1][2][3][4][5][6]. By carefully designing them and selecting an appropriate preparation method and structure-building components, it is possible to obtain nanocarriers with extended circulation time in the bloodstream, which will provide their cargo to the target site.…”