Nanodiamond-Gadolinium(III) Aggregates for Tracking Cancer Growth in Vivo at High Field

Nikhil Rammohan, Keith W. MacRenaris, Laura K. Moore, Giacomo Parigi, Daniel J. Mastarone, Lisa M. Manus, Laura M. Lilley, Adam T. Preslar, Emily A. Waters, Abigail Filicko, Claudio Luchinat, Dean Ho, Thomas J. Meade*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

The ability to track labeled cancer cells in vivo would allow researchers to study their distribution, growth, and metastatic potential within the intact organism. Magnetic resonance (MR) imaging is invaluable for tracking cancer cells in vivo as it benefits from high spatial resolution and the absence of ionizing radiation. However, many MR contrast agents (CAs) required to label cells either do not significantly accumulate in cells or are not biologically compatible for translational studies. We have developed carbon-based nanodiamond-gadolinium(III) aggregates (NDG) for MR imaging that demonstrated remarkable properties for cell tracking in vivo. First, NDG had high relaxivity independent of field strength, a finding unprecedented for gadolinium(III) [Gd(III)]-nanoparticle conjugates. Second, NDG demonstrated a 300-fold increase in the cellular delivery of Gd(III) compared to that of clinical Gd(III) chelates without sacrificing biocompatibility. Further, we were able to monitor the tumor growth of NDG-labeled flank tumors by T1- and T2-weighted MR imaging for 26 days in vivo, longer than was reported for other MR CAs or nuclear agents. Finally, by utilizing quantitative maps of relaxation times, we were able to describe tumor morphology and heterogeneity (corroborated by histological analysis), which would not be possible with competing molecular imaging modalities.

Original languageEnglish (US)
Pages (from-to)7551-7564
Number of pages14
JournalNano letters
Volume16
Issue number12
DOIs
StatePublished - Dec 14 2016

Funding

This work was supported the National Institutes of Health (NIH) Centers of Cancer Nanotechnology Excellence initiative of the National Cancer Institute under award no. U54CA151880, the NIH National Institute of Biomedical Imaging and Bioengineering under award no. R01EB005866, the National Science Foundation Biomaterials grant no. DMR-1105060, and the Rosenberg Cancer Foundation. Metal analysis was performed at the Northwestern University (NU) Quantitative Bioelemental Imaging Center, generously supported by NASA Ames Research Center grant no. NNA04CC36G. C.L. and G.P. acknowledge MIUR PRIN 2012SK7ASN, the European Commission, contracts BioMedBridges 284209 and pNMR 317127, and the EU ESFRI Instruct Core Centre CERM. All of these core facilities are generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center.

Keywords

  • MRI
  • Nanodiamonds
  • cancer
  • gadolinium
  • in vivo

ASJC Scopus subject areas

  • General Chemistry
  • Condensed Matter Physics
  • Mechanical Engineering
  • Bioengineering
  • General Materials Science

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