Multivalent Viral Capsids with Internal Cargo for Fibrin Imaging

Obermeyer, Allie C.; Capehart, Stacy L.; Jarman, John B.; Francis, Matthew B.

doi:10.1371/journal.pone.0100678

Multivalent Viral Capsids with Internal Cargo for Fibrin Imaging

Journal Article · Tue Jun 24 00:00:00 EDT 2014 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0100678· OSTI ID:1627708

Obermeyer, Allie C. ^[1]; Capehart, Stacy L. ^[2]; Jarman, John B. ^[2]; Francis, Matthew B. ^[3]

University of California, Berkeley, CA (United States); DOE/OSTI
University of California, Berkeley, CA (United States)
University of California, Berkeley, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Thrombosis is the cause of many cardiovascular syndromes and is a significant contributor to life-threatening diseases, such as myocardial infarction and stroke. Thrombus targeted imaging agents have the capability to provide molecular information about pathological clots, potentially improving detection, risk stratification, and therapy of thrombosis-related diseases. Nanocarriers are a promising platform for the development of molecular imaging agents as they can be modified to have external targeting ligands and internal functional cargo. In this work, we report the synthesis and use of chemically functionalized bacteriophage MS2 capsids as biomolecule-based nanoparticles for fibrin imaging. The capsids were modified using an oxidative coupling reaction, conjugating ~90 copies of a fibrin targeting peptide to the exterior of each protein shell. The ability of the multivalent, targeted capsids to bind fibrin was first demonstrated by determining the impact on thrombin-mediated clot formation. The modified capsids out-performed the free peptides and were shown to inhibit clot formation at effective concentrations over ten-fold lower than the monomeric peptide alone. The installation of near-infrared fluorophores on the interior surface of the capsids enabled optical detection of binding to fibrin clots. The targeted capsids bound to fibrin, exhibiting higher signal-to-background than control, non-targeted MS2-based nanoagents. The in vitro assessment of the capsids suggests that fibrin-targeted MS2 capsids could be used as delivery agents to thrombi for diagnostic or therapeutic applications.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: Department of Defense (DoD); National Science Foundation (NSF); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1627708

Journal Information:: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 6 Vol. 9; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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fluorescence imaging
magnetic resonance imaging
matrix-assisted laser desorption ionization time-of-flight mass spectrometry
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Multivalent Viral Capsids with Internal Cargo for Fibrin Imaging

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