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Receptor-targeted iron oxide nanoparticles for molecular MR imaging of inflamed atherosclerotic plaques

Tu, Chuqiao and Ng, Thomas S. C. and Sohi, Hargun K. and Palko, Heather A. and House, Adrian and Jacobs, Russell E. and Louie, Angelique Y. (2011) Receptor-targeted iron oxide nanoparticles for molecular MR imaging of inflamed atherosclerotic plaques. Biomaterials, 32 (29). pp. 7209-7216. ISSN 0142-9612. PMCID PMC3148412. https://resolver.caltech.edu/CaltechAUTHORS:20110928-081451527

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Abstract

In a number of literature reports iron oxide nanoparticles have been investigated for use in imaging atherosclerotic plaques and found to accumulate in plaques via uptake by macrophages, which are critical in the process of atheroma initiation, propagation, and rupture. However, the uptake of these agents is non-specific; thus the labeling efficiency for plaques in vivo is not ideal. We have developed targeted agents to improve the efficiency for labeling macrophage-laden plaques. These probes are based on iron oxide nanoparticles coated with dextran sulfate, a ligand of macrophage scavenger receptor type A (SR-A). We have sulfated dextran-coated iron oxide nanoparticles (DIO) with sulfur trioxide, thereby targeting our nanoparticle imaging agents to SR-A. The sulfated DIO (SDIO) remained mono-dispersed and had an average hydrodynamic diameter of 62 nm, an r_1 relaxivity of 18.1 mM^(−1) s^(−1), and an r_2 relaxivity of 95.8 mM^(−1) s^(−1) (37 °C, 1.4 T). Cell studies confirmed that these nanoparticles were nontoxic and specifically targeted to macrophages. In vivo MRI after intravenous injection of the contrast agent into an atherosclerotic mouse injury model showed substantial signal loss on the injured carotid at 4 and 24 h post-injection of SDIO. No discernable signal decrease was seen at the control carotid and only mild signal loss was observed for the injured carotid post-injection of non-sulfated DIO, indicating preferential uptake of the SDIO particles at the site of atherosclerotic plaque. These results indicate that SDIO can facilitate MRI detection and diagnosis of vulnerable plaques in atherosclerosis.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.biomaterials.2011.06.026DOIArticle
http://www.sciencedirect.com/science/article/pii/S0142961211006910PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148412/PubMed CentralArticle
ORCID:
AuthorORCID
Jacobs, Russell E.0000-0002-1382-8486
Additional Information:© 2011 Elsevier Ltd. Received 20 April 2011; Accepted 8 June 2011. Available online 13 July 2011. The authors wish to acknowledge the National Institute of Health (EB008576-01, and EB000993), the Beckman Institute at Caltech, the Center for Molecular and Genomic Imaging at UC Davis (U24 CA 110804), and the NMR award of the University of California, Davis for support of this work. We thank Dr. Xuchu Ma, Dr. Jai Woong Seo, and Bita Alaghebandan for help in IR spectroscopy, zeta potential, and animal handling, respectively.
Funders:
Funding AgencyGrant Number
NIHEB008576-01
NIHEB000993
Caltech Beckman InstituteUNSPECIFIED
UC Davis Center for Molecular and Genomic ImagingU24 CA 110804
Subject Keywords:Nanoparticles; Imaging agents; MRI (magnetic resonance imaging); Molecular imaging; Macrophages; Inflammation
Issue or Number:29
PubMed Central ID:PMC3148412
Record Number:CaltechAUTHORS:20110928-081451527
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20110928-081451527
Official Citation:Chuqiao Tu, Thomas S.C. Ng, Hargun K. Sohi, Heather A. Palko, Adrian House, Russell E. Jacobs, Angelique Y. Louie, Receptor-targeted iron oxide nanoparticles for molecular MR imaging of inflamed atherosclerotic plaques, Biomaterials, Volume 32, Issue 29, October 2011, Pages 7209-7216, ISSN 0142-9612, 10.1016/j.biomaterials.2011.06.026. (http://www.sciencedirect.com/science/article/pii/S0142961211006910)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:25458
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:28 Sep 2011 15:50
Last Modified:03 Oct 2019 03:06

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