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Effect of Gold Nanoparticle Size and Coating on Labeling Monocytes for CT Tracking

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† ‡ § †Department of Radiology, ‡Department of Bioengineering, and §Department of Medicine, Division of Cardiovascular Medicine, Perelman School of Medicine of the University of Pennsylvania, 3400 Spruce Street, 1 Silverstein, Philadelphia, Pennsylvania 19104, United States,
*E-mail: [email protected]. Phone: 215-746-1382. Fax: 240-368-8096.
Cite this: Bioconjugate Chem. 2017, 28, 1, 260–269
Publication Date (Web):November 8, 2016
https://doi.org/10.1021/acs.bioconjchem.6b00566
Copyright © 2016 American Chemical Society
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    Abstract

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    With advances in cell therapies, interest in cell tracking techniques to monitor the migration, localization, and viability of these cells continues to grow. X-ray computed tomography (CT) is a cornerstone of medical imaging but has been limited in cell tracking applications due to its low sensitivity toward contrast media. In this study, we investigate the role of size and surface functionality of gold nanoparticles for monocyte uptake to optimize the labeling of these cells for tracking in CT. We synthesized gold nanoparticles (AuNP) that range from 15 to 150 nm in diameter and examined several capping ligands, generating 44 distinct AuNP formulations. In vitro cytotoxicity and uptake experiments were performed with the RAW 264.7 monocyte cell line. The majority of formulations at each size were found to be biocompatible, with only certain 150 nm PEG functionalized particles reducing viability at high concentrations. High uptake of AuNP was found using small capping ligands with distal carboxylic acids (11-MUA and 16-MHA). Similar uptake values were found with intermediate sizes (50 and 75 nm) of AuNP when coated with 2000 MW poly(ethylene-glycol) carboxylic acid ligands (PCOOH). Low uptake values were observed with 15, 25, 100, and 150 nm PCOOH AuNP, revealing interplay between size and surface functionality. Transmission electron microscopy (TEM) and CT performed on cells revealed similar patterns of high gold uptake for 50 nm PCOOH and 75 nm PCOOH AuNP. These results demonstrate that highly negatively charged carboxylic acid coatings for AuNP provide the greatest internalization of AuNP in monocytes, with a complex dependency on size.

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.bioconjchem.6b00566.

    • Synthesis details for each nanoparticle size, including ligand concentrations and centrifuge parameters, additional characterization data of the gold nanoparticle formulations, and the relationship between attenuation and uptake of gold in monocytes shown. (PDF)

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