Abstract
Over the past two decades, measurements of carbon nanotube toxicity and biodistribution have yielded a wide range of results. Properties such as nanotube type (single-walled vs. multi-walled), purity, length, aggregation state, and functionalization, as well as route of administration, greatly affect both the biocompatibility and biodistribution of carbon nanotubes. These differences suggest that generalizable conclusions may be elusive and that studies must be material- and application-specific. Here, we assess the short- and long-term biodistribution and biocompatibility of a single-chirality DNA-encapsulated single-walled carbon nanotube complex upon intravenous administration that was previously shown to function as an in-vivo reporter of endolysosomal lipid accumulation. Regarding biodistribution and fate, we found bulk specificity to the liver and >90% signal attenuation by 14 days in mice. Using near-infrared hyperspectral microscopy to measure single nanotubes, we found low-level, long-term persistence in organs such as the heart, liver, lung, kidney, and spleen. Measurements of histology, animal weight, complete blood count; biomarkers of organ function all suggest short- and long-term biocompatibility. This work suggests that carbon nanotubes can be used as preclinical research tools in-vivo without affecting acute or long-term health.
Original language | English |
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Article number | e0226791 |
Journal | PLoS ONE |
Volume | 15 |
Issue number | 5 |
DOIs | |
State | Published - May 2020 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2020 Galassi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding
This work was supported in part by the NIH New Innovator Award (DP2-HD075698), NIDDK (R01-DK114321), CTSC (UL1-TR002384) NCI (R01-CA215719), the Cancer Center Support Grant (P30-CA008748), the National Science Foundation CAREER Award (1752506), the Ara Parseghian Medical Research Fund, the American Cancer Society Research Scholar Grant (GC230452), the Pershing Square Sohn Cancer Research Alliance, the Honorable Tina Brozman Foundation for Ovarian Cancer Research, the Expect Miracles Foundation - Financial Services Against Cancer, the Anna Fuller Fund, the Louis V. Gerstner Jr. Young Investigator’s Fund, the Frank A. Howard Scholars Program, MSK’s Cycle for Survival’s Equinox Innovation Award in Rare Cancers, the Alan and Sandra Gerry Metastasis Research Initiative, Mr. William H. Goodwin and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research, the Experimental Therapeutics Center, the Imaging & Radiation Sciences Program, and the Center for Molecular Imaging and Nanotechnology of Memorial Sloan Kettering Cancer Center. R.E.S. is supported by 1K08DK101754, 1R03DK117252, R01CA234614, DOD grant W81XWH1810237, and is a Irma Hirschl Trust Research Award Scholar. We would like to thank Y. Shamay, R. Williams, H. Baker, C. Cupo, M. Kim and J. Budhathoki-Uprety for helpful discussions. P.Jena for MATLAB code. We also acknowledge the Molecular Cytology Core Facility at Memorial Sloan Kettering Cancer Center and the Electron Microscopy & Histology Core Facility at Weill Cornell Medicine.
Funders | Funder number |
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Alan and Sandra Gerry Metastasis Research Initiative | |
Anna Fuller Fund | |
Cancer Center Support | P30-CA008748 |
National Science Foundation | 1752506 |
National Institutes of Health | DP2-HD075698 |
U.S. Department of Defense | W81XWH1810237 |
American Cancer Society | GC230452 |
National Cancer Institute | R01-CA215719, R01CA234614 |
National Institute of Diabetes and Digestive and Kidney Diseases | K08DK101754, R01-DK114321 |
Honorable Tina Brozman Foundation | |
Irma T. Hirschl Trust | |
Clinical and Translational Science Collaborative of Cleveland, School of Medicine, Case Western Reserve University | UL1-TR002384 |
Pershing Square Sohn Cancer Research Alliance | |
Commonwealth Foundation for Cancer Research Foundation | 1R03DK117252, 1K08DK101754 |
Ara Parseghian Medical Research Fund | |
Expect Miracles Foundation |