Issue 41, 2019

Hydroxyapatite-binding micelles for the detection of vascular calcification in atherosclerosis

Abstract

Atherosclerosis is a chronic disease characterized by the formation of calcified, arterial plaques. Microcalcifications (5 μm to 100 μm), mainly composed of hydroxyapatite (HA, Ca5(PO4)3(OH)), develop in the fibrous caps of atherosclerotic plaques and can trigger plaque rupture due to the loss of compliance and elasticity. Ultimately, plaque rupture can cause arterial occlusion and embolization and result in ischemic events such as strokes and myocardial infarctions. Unfortunately, current imaging technologies used to detect calcifications are limited by low signal-to-noise ratio or use invasive procedures that pose risk of arterial dissection. To mitigate these drawbacks, in our study, we developed a novel, fluorescently-labeled peptide amphiphile micelle (PAM) that uses a 12 amino acid HA-binding peptide (HABP) [SVSVGMKPSPRP] to target and detect atherosclerotic calcification (HA PAM). Our results show HA PAMs can successfully target HA microcrystals with a strong binding affinity (KD = 6.26 ± 1.2 μM) in vitro. In addition, HA PAMs detected HA mineralization (HA PAM vs. non-targeting micelle, p ≤ 0.001; HA PAM vs. scrambled HABP PAM, p ≤ 0.01) formed by calcifying mouse aortic vascular smooth muscle cells (MOVAS). Moreover, HA PAMs successfully detected calcifications in atherosclerotic mouse models as well as in patient-derived arteries. Our studies show that HA PAMs show promise as calcium-targeting nanoparticles for the detection of calcifications in atherosclerosis.

Graphical abstract: Hydroxyapatite-binding micelles for the detection of vascular calcification in atherosclerosis

Supplementary files

Article information

Article type
Paper
Submitted
05 Way 2019
Accepted
18 Way 2019
First published
25 Way 2019

J. Mater. Chem. B, 2019,7, 6449-6457

Hydroxyapatite-binding micelles for the detection of vascular calcification in atherosclerosis

D. D. Chin, J. Wang, M. Mel de Fontenay, A. Plotkin, G. A. Magee and E. J. Chung, J. Mater. Chem. B, 2019, 7, 6449 DOI: 10.1039/C9TB01918A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements