Adiponectin-coated nanoparticles for enhanced imaging of atherosclerotic plaques

Abstract

Background: Atherosclerosis is a leading cause of mortality in the Western world, and plaque diagnosis is still a challenge in cardiovascular medicine. The main focus of this study was to make atherosclerotic plaques visible using targeted nanoparticles for improved imaging. Today various biomarkers are known to be involved in the pathophysiologic scenario of atherosclerotic plaques. One promising new candidate is the globular domain of the adipocytokine adiponectin (gAd), which was used as a targeting sequence in this study. Methods: gAd was coupled to two different types of nanoparticles, namely protamine-oligonucleotide nanoparticles, known as proticles, and sterically stabilized liposomes. Both gAd-targeted nanoparticles were investigated for their potency to characterize critical scenarios within early and advanced atherosclerotic plaque lesions using an atherosclerotic mouse model. Aortic tissue from wild type and apolipoprotein E-deficient mice, both fed a high-fat diet, were stained with either fluorescent-labeled gAd or gAd-coupled nanoparticles. Ex vivo imaging was performed using confocal laser scanning microscopy. Results: gAd-targeted sterically stabilized liposomes generated a strong signal by accumulating at the surface of atherosclerotic plaques, while gAd-targeted proticles became internalized and showed more spotted plaque staining. Conclusion: Our results offer a promising perspective for enhanced in vivo imaging using gAd-targeted nanoparticles. By means of nanoparticles, a higher payload of signal emitting molecules could be transported to atherosclerotic plaques. Additionally, the opportunity is opened up to visualize different regions in the plaque scenario, depending on the nature of the nanoparticle used.

Nanotechnology-Based Delivery Systems for Antimicrobial Peptides

“…Different conjugation chemistries have been studied for effective drug loading and delivery. Examples of these chemistries include the conjugation of RR-11a endopeptidase to liposomes using the amine/carboxyl chemistry [149], the polyclonal Rabbit IgG conjugated to AuNPs using the amine/carboxylate chemistry [150], S2P peptide (CRTLTVRKC) conjugated to chitosan NPs through the amine/carboxylate, thiol/maleimide chemistry [151], liposome functionalized with adiponectin, globular domain by thiol/maleimide chemistry [152], and the J18 RNA aptamer conjugated to AuNPs by the base-pairing hybridization [153]. Immobilization of the biomolecules/AMPs on the NPs can occur in two ways; i.e., the AMPs are either temporarily (reversible) or permanently (irreversible) tethered on or within the NPs.…”

Combating atherosclerosis with targeted nanomedicines: recent advances and future prospective

“…Atherosclerotic molecular markers (AMMs) are the major targets, which can be exploited for the development of targeted NPs conjugated with specific ligands in order to deliver imaging/therapeutic agents into the lesions by targeting designated AMM. 35 , 36 In the atherosclerotic plaques, cellular components are exposed to the circulation due to the high expression levels of certain molecules, by which they can be targeted by the NPs. Additionally, the intra-plaque components are accessible by NPs through the cellular gaps of the endothelial cells.…”