CD44 Targeting Magnetic Glyconanoparticles for Atherosclerotic Plaque Imaging

Abstract

Purpose The cell surface adhesion molecule CD44 plays important roles in the initiation and development of atherosclerotic plaques. We aim to develop nanoparticles that can selectively target CD44 for the non-invasive detection of atherosclerotic plaques by magnetic resonance imaging. Methods Magnetic glyco-nanoparticles with hyaluronan immobilized on the surface have been prepared. The binding of these nanoparticles with CD44 in vitro was evaluated by enzyme linked immunosorbent assay, flow cytometry and confocal microscopy. In vivo magnetic resonance imaging of plaques was performed on an atherosclerotic rabbit model. Results The magnetic glyconanoparticles can selectively bind CD44. In T2* weighted magnetic resonance images acquired in vivo, significant contrast changes in aorta walls were observed with a very low dose of the magnetic nanoparticles, allowing the detection of atherosclerotic plaques. Furthermore, imaging could be performed without significant delay after probe administration. The selectivity of hyaluronan nanoparticles in plaque imaging was established by several control experiments. Conclusions Magnetic nanoparticles bearing surface hyaluronan enabled the imaging of atherosclerotic plaques in vivo by magnetic resonance imaging. The low dose of nanoparticles required, the possibility to image without much delay and the high biocompatibility are the advantages of these nanoparticles as contrast agents for plaque imaging.

Nanomedicines for dysfunctional macrophage-associated diseases

“…It binds specifically to the membrane receptor CD163 over-expressed by macrophages at inflammatory sites such as atherosclerotic plaques [218]. El-Dakdouki et al decorated magnetic glyconanoparticles with hyaluronan, which selectively binds to CD44 overexpressed by macrophages within vulnerable plaques [219]. As a ligand for SR-A overexpressed by activated macrophages within atherosclerotic plaques, dextran sulfate (DS) was employed by You et al to coat SPIO for imaging of atherosclerosis [220].…”

Hyaluronic acid-decorated reconstituted high density lipoprotein targeting atherosclerotic lesions

“…In recent years, many researches had employed HA to decorate nanocarriers for anticancer drugs to improve the targeting efficiency to solid tumors via CD44-mediated uptake, while overlooking the valuable function of HA in diagnosis and therapy of atherosclerosis [18e21]. The upregulated CD44 at atherosclerotic lesions coupled with the high affinity HA to CD44 at inflammatory sites render it attractive to utilize HA/CD44 interactions for effective plaque targeting [22,23]. Heretofore, barely any research was reported on HA-modified nanocarriers to achieve atherosclerotic lesions-targeted drug delivery.…”

Radiosensitizing and Hyperthermic Properties of Hyaluronan Conjugated, Dextran‐Coated Ferric Oxide Nanoparticles: Implications for Cancer Stem Cell Therapy

“…This lack of radiosensitization was also absent in cells that were enriched for the highest expression levels of CD44 using a cell sorting approach. The HA-DESPIONs used in this study have previously been shown to be detectable in tumors and atherosclerotic plaques using static magnetic fields to provide contrast for magnetic resonance imaging [11,33]. This is because stabilized superparamagnetic iron oxide nanoparticles are characterized by inherently high T2/T2 * relaxivity causing strong local inhomogeneities which can be detected as hypointense areas.…”