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Gerstenhaber JA , Marcinkiewicz C , Barone FC , Sternberg M , D'Andrea MR , Lelkes PI , Feuerstein GZ
Biocompatibility studies of fluorescent diamond particles-(NV)~800nm (part V): in vitro kinetics and in vivo localization in rat liver following long-term exposure
Int J Nanomedicine. 2019 ;14 :6451-6464
PMID: 31496697    PMCID: PMC6697667   
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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.
1178-2013 Gerstenhaber, Jonathan A Marcinkiewicz, Cezary Barone, Frank C Sternberg, Mark D'Andrea, Michael R Lelkes, Peter I Feuerstein, Giora Z Journal Article New Zealand Int J Nanomedicine. 2019 Aug 12;14:6451-6464. doi: 10.2147/IJN.S209663. eCollection 2019.