Biocompatibility studies of fluorescent diamond particles-(NV)∼800nm (part V): in vitro kinetics and in vivo localization in rat liver following long-term exposure
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 Feuerstein21Department of Bioengineering, College of Engineering, Temple University, Philadelphia, PA, USA; 2Debina Diagnostic Inc., Newtown Squar...
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Dove Medical Press
2019
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oai:doaj.org-article:1c78ea90a25f4698a8b0678274af39fd2021-12-02T05:03:56ZBiocompatibility studies of fluorescent diamond particles-(NV)∼800nm (part V): in vitro kinetics and in vivo localization in rat liver following long-term exposure1178-2013https://doaj.org/article/1c78ea90a25f4698a8b0678274af39fd2019-08-01T00:00:00Zhttps://www.dovepress.com/biocompatibility-studies-of-fluorescent-diamond-particles-nv-800nm-par-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jonathan 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 Feuerstein21Department 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 workBackground: 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 nanodiamondsGerstenhaber JAMarcinkiewicz CBarone FCSternberg MD’Andrea MRLelkes PIFeuerstein GZDove Medical PressarticleCarbon NanoparticlesHepG-2 cellsHUVECNear Infra-Red imagingConfocal Fluorescent MicroscopyHepatic LobuleSubcellular distributionCytokinesisCellular Uptake of ParticlesLiver sinusoidsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 6451-6464 (2019) |
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DOAJ |
| collection |
DOAJ |
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EN |
| topic |
Carbon Nanoparticles HepG-2 cells HUVEC Near Infra-Red imaging Confocal Fluorescent Microscopy Hepatic Lobule Subcellular distribution Cytokinesis Cellular Uptake of Particles Liver sinusoids Medicine (General) R5-920 |
| spellingShingle |
Carbon Nanoparticles HepG-2 cells HUVEC Near Infra-Red imaging Confocal Fluorescent Microscopy Hepatic Lobule Subcellular distribution Cytokinesis Cellular Uptake of Particles Liver sinusoids Medicine (General) R5-920 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 |
| description |
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 Feuerstein21Department 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 workBackground: 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 |
| format |
article |
| author |
Gerstenhaber JA Marcinkiewicz C Barone FC Sternberg M D’Andrea MR Lelkes PI Feuerstein GZ |
| author_facet |
Gerstenhaber JA Marcinkiewicz C Barone FC Sternberg M D’Andrea MR Lelkes PI Feuerstein GZ |
| author_sort |
Gerstenhaber JA |
| title |
Biocompatibility studies of fluorescent diamond particles-(NV)∼800nm (part V): in vitro kinetics and in vivo localization in rat liver following long-term exposure |
| title_short |
Biocompatibility studies of fluorescent diamond particles-(NV)∼800nm (part V): in vitro kinetics and in vivo localization in rat liver following long-term exposure |
| title_full |
Biocompatibility studies of fluorescent diamond particles-(NV)∼800nm (part V): in vitro kinetics and in vivo localization in rat liver following long-term exposure |
| title_fullStr |
Biocompatibility studies of fluorescent diamond particles-(NV)∼800nm (part V): in vitro kinetics and in vivo localization in rat liver following long-term exposure |
| title_full_unstemmed |
Biocompatibility studies of fluorescent diamond particles-(NV)∼800nm (part V): in vitro kinetics and in vivo localization in rat liver following long-term exposure |
| title_sort |
biocompatibility studies of fluorescent diamond particles-(nv)∼800nm (part v): in vitro kinetics and in vivo localization in rat liver following long-term exposure |
| publisher |
Dove Medical Press |
| publishDate |
2019 |
| url |
https://doaj.org/article/1c78ea90a25f4698a8b0678274af39fd |
| work_keys_str_mv |
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