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Biocompatibility studies of fluorescent diamond particles-(NV)∼800nm (part V): in vitro kinetics and in vivo localization in rat liver following long-term exposure

Authors Gerstenhaber JA, Marcinkiewicz C, Barone FC, Sternberg M, D’Andrea MR, Lelkes PI, Feuerstein GZ

Received 22 March 2019

Accepted for publication 9 July 2019

Published 12 August 2019 Volume 2019:14 Pages 6451—6464


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Melinda Thomas

Peer reviewer comments 2

Editor who approved publication: Dr Thomas Webster

Jonathan A Gerstenhaber,1,* Cezary Marcinkiewicz,1,2,* Frank C Barone,3 Mark Sternberg,2 Michael R D’Andrea,4 Peter I Lelkes,1 Giora Z Feuerstein2

1Department of Bioengineering, College of Engineering, Temple University, Philadelphia, PA, USA; 2Debina Diagnostic Inc., Newtown Square, PA, USA; 3SUNY Downstate Medical Center, Department of Neurology, Brooklyn, NY, USA; 4Analytical Biological Services Inc., Wilmington, DE, USA

*These authors contributed equally to this work

Background: We recently reported on long-term comprehensive biocompatibility and biodistribution study of fluorescent nanodiamond particles (NV)-Z-average 800nm (FNDP-(NV)) in rats. FNDP-(NV) primary deposition was found in the liver, yet liver function tests remained normal.
Purpose: The present study aimed to gain preliminary insights on discrete localization of FNDP-(NV) in liver cells of the hepatic lobule unit and venous micro-vasculature. Kinetics of FDNP-(NV) uptake into liver cells surrogates in culture was conducted along with cell cytokinesis as markers of cells’ viability.
Methods: Preserved liver specimens from a pilot consisting of two animals which were stained for cytoskeletal elements (fluorescein-isothiocyanate-phalloidin) were examined for distribution of FNDP-(NV) by fluorescent microscopy (FM) and Confocal-FM (CFM) using near infra-red fluorescence (NIR). Hepatocellular carcinoma cells (HepG-2) and human umbilical vein endothelial cells (HUVEC) were cultured with FNDP-(NV) and assayed for particle uptake and location using spectrophotometric technology and microscopy.
Results: HepG-2 and HUVEC displayed rapid (<30 mins) onset and concentration-dependent FNDP-(NV) internalization and formation of peri-nuclear corona. FM/CFM of liver sections revealed FNDP-(NV) presence throughout the hepatic lobules structures marked by spatial distribution, venous microvascular spaces and parenchyma and non-parenchyma cells.
Conclusion: The robust presence of FNDP-(NV) throughout the hepatic lobules including those internalized within parenchyma cells and agglomerates in the liver venous micro-circulation were not associated with macro or micro histopathological signs nor vascular lesions. Cells cultures indicated normal cytokinesis in cells containing FNDP-(NV) agglomerates. Liver parenchyma cells and the liver microcirculation remain agnostic to presence of FNDP-(NV) in the sinusoids or internalized in the hepatic cells.

Keywords: carbon nanoparticles, HepG-2 cells, HUVEC, subcellular distribution, cytokinesis, cellular uptake of nanodiamonds

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