Effects of Fluorescent Diamond Particles FDP-NV-800nm on Essential Biochemical Functions of Primary Human Umbilical Vein Cells and Human Hepatic Cell Line, HepG-2 in vitro (Part VI): Acute Biocompatibility Studies

Cezary Marcinkiewicz,1,2 Peter I Lelkes,2 Mark Sternberg,1 Giora Z Feuerstein1 1Debina Diagnostics Inc., Newtown Square, PA, USA; 2College of Engineering, Temple University, Philadelphia, PA, USACorrespondence: Giora Z FeuersteinDebina Diagnostics Inc., Newtown Square, PA, USAEmail giorafeuerstein@g...

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Autores principales:	Marcinkiewicz C, Lelkes PI, Sternberg M, Feuerstein GZ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	near infra-red hepg-2 cells huvec cell proliferation apoptosis mapk kinase Medical technology R855-855.5 Chemical technology TP1-1185
Acceso en línea:	https://doaj.org/article/3e9fad61d02f4b299f6ce5eb30863791
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spelling	oai:doaj.org-article:3e9fad61d02f4b299f6ce5eb308637912021-12-02T08:26:37ZEffects of Fluorescent Diamond Particles FDP-NV-800nm on Essential Biochemical Functions of Primary Human Umbilical Vein Cells and Human Hepatic Cell Line, HepG-2 in vitro (Part VI): Acute Biocompatibility Studies1177-8903https://doaj.org/article/3e9fad61d02f4b299f6ce5eb308637912020-10-01T00:00:00Zhttps://www.dovepress.com/effects-of-fluorescent-diamond-particles-fdp-nv-800nm-on-essential-bio-peer-reviewed-article-NSAhttps://doaj.org/toc/1177-8903Cezary Marcinkiewicz,1,2 Peter I Lelkes,2 Mark Sternberg,1 Giora Z Feuerstein1 1Debina Diagnostics Inc., Newtown Square, PA, USA; 2College of Engineering, Temple University, Philadelphia, PA, USACorrespondence: Giora Z FeuersteinDebina Diagnostics Inc., Newtown Square, PA, USAEmail giorafeuerstein@gmail.comBackground: Recently, we reported the safety and biocompatibility of fluorescent diamond particles, FDP-NV-Z-800nm (FDP-NV) injected intravenously into rats, where no morbidity and mortality were noted over a period of 3 months. The acute effects of FDP-NV-800nm particles on cultured human endothelial and hepatic cells remain unexplored.Purpose: In this study, we aimed to explore select cellular and biochemical functions in cultured human umbilical endothelial cells (HUVEC) and a human hepatic cancer cell line (HepG-2) exposed to FDP-NV-800 in vitro at exposure levels within the pharmacokinetics (Cmax and the nadir) previously reported in vivo.Methods: Diverse cellular and biochemical functions were monitored, which cumulatively can provide insights into some vital cellular functions. Cell proliferation and migration were assessed by quantitative microscopy. Mitochondrial metabolic functions were tested by the MTT assay, and cytosolic esterase activity was studied by the calcein AM assay. Chaperons (CHOP), BiP and apoptosis (caspase-3 activation) were monitored by using Western blot (WB). MAPK Erk1/2 signaling was assessed by the detection of the phosphorylated form of the protein (P-Erk 1/2) and its translocation into the cell nucleus.Results: At all concentrations tested (0.001– 0.1mg/mL), FDP-NV did not affect any of the biomarkers of cell integrity of HepG2 cells. In contrast, the proliferation of HUVEC was affected at the highest concentration tested (0.1mg/mL, Cmax). Exposure of HUVEC to (0.01 mg/mL) FDP-NV had a mild-moderate effect on cell proliferation as evident in the MTT assay and was absent when proliferation was assessed by direct cell counting or by using the calcein AM assays. In both cell types, exposure to the highest concentration (0.1 mg/mL) of FDP-NV did neither affect FBS-stimulated cell signaling (MAPK Erk1/2 phosphorylation) nor did it activate of Caspase 3.Conclusion: Our data suggest that FDP-NV-800nm are largely biocompatible with HepG-2 cells proliferation within the pharmacokinetic data reported previously. In contrast, HUVEC proliferation at the highest exposure dose (0.1 mg/mL) responded adversely with respect to several biomarkers of cell integrity. However, since the Cmax levels are very short-living, the risk for endothelial injury is likely minimal for slow rate cell proliferation such as endothelial cells.Keywords: near infra-red, HepG-2 cells, HUVEC, cell proliferation, apoptosis, MAPK kinaseMarcinkiewicz CLelkes PISternberg MFeuerstein GZDove Medical Pressarticlenear infra-redhepg-2 cellshuveccell proliferationapoptosismapk kinaseMedical technologyR855-855.5Chemical technologyTP1-1185ENNanotechnology, Science and Applications, Vol Volume 13, Pp 103-118 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	near infra-red hepg-2 cells huvec cell proliferation apoptosis mapk kinase Medical technology R855-855.5 Chemical technology TP1-1185
spellingShingle	near infra-red hepg-2 cells huvec cell proliferation apoptosis mapk kinase Medical technology R855-855.5 Chemical technology TP1-1185 Marcinkiewicz C Lelkes PI Sternberg M Feuerstein GZ Effects of Fluorescent Diamond Particles FDP-NV-800nm on Essential Biochemical Functions of Primary Human Umbilical Vein Cells and Human Hepatic Cell Line, HepG-2 in vitro (Part VI): Acute Biocompatibility Studies
description	Cezary Marcinkiewicz,1,2 Peter I Lelkes,2 Mark Sternberg,1 Giora Z Feuerstein1 1Debina Diagnostics Inc., Newtown Square, PA, USA; 2College of Engineering, Temple University, Philadelphia, PA, USACorrespondence: Giora Z FeuersteinDebina Diagnostics Inc., Newtown Square, PA, USAEmail giorafeuerstein@gmail.comBackground: Recently, we reported the safety and biocompatibility of fluorescent diamond particles, FDP-NV-Z-800nm (FDP-NV) injected intravenously into rats, where no morbidity and mortality were noted over a period of 3 months. The acute effects of FDP-NV-800nm particles on cultured human endothelial and hepatic cells remain unexplored.Purpose: In this study, we aimed to explore select cellular and biochemical functions in cultured human umbilical endothelial cells (HUVEC) and a human hepatic cancer cell line (HepG-2) exposed to FDP-NV-800 in vitro at exposure levels within the pharmacokinetics (Cmax and the nadir) previously reported in vivo.Methods: Diverse cellular and biochemical functions were monitored, which cumulatively can provide insights into some vital cellular functions. Cell proliferation and migration were assessed by quantitative microscopy. Mitochondrial metabolic functions were tested by the MTT assay, and cytosolic esterase activity was studied by the calcein AM assay. Chaperons (CHOP), BiP and apoptosis (caspase-3 activation) were monitored by using Western blot (WB). MAPK Erk1/2 signaling was assessed by the detection of the phosphorylated form of the protein (P-Erk 1/2) and its translocation into the cell nucleus.Results: At all concentrations tested (0.001– 0.1mg/mL), FDP-NV did not affect any of the biomarkers of cell integrity of HepG2 cells. In contrast, the proliferation of HUVEC was affected at the highest concentration tested (0.1mg/mL, Cmax). Exposure of HUVEC to (0.01 mg/mL) FDP-NV had a mild-moderate effect on cell proliferation as evident in the MTT assay and was absent when proliferation was assessed by direct cell counting or by using the calcein AM assays. In both cell types, exposure to the highest concentration (0.1 mg/mL) of FDP-NV did neither affect FBS-stimulated cell signaling (MAPK Erk1/2 phosphorylation) nor did it activate of Caspase 3.Conclusion: Our data suggest that FDP-NV-800nm are largely biocompatible with HepG-2 cells proliferation within the pharmacokinetic data reported previously. In contrast, HUVEC proliferation at the highest exposure dose (0.1 mg/mL) responded adversely with respect to several biomarkers of cell integrity. However, since the Cmax levels are very short-living, the risk for endothelial injury is likely minimal for slow rate cell proliferation such as endothelial cells.Keywords: near infra-red, HepG-2 cells, HUVEC, cell proliferation, apoptosis, MAPK kinase
format	article
author	Marcinkiewicz C Lelkes PI Sternberg M Feuerstein GZ
author_facet	Marcinkiewicz C Lelkes PI Sternberg M Feuerstein GZ
author_sort	Marcinkiewicz C
title	Effects of Fluorescent Diamond Particles FDP-NV-800nm on Essential Biochemical Functions of Primary Human Umbilical Vein Cells and Human Hepatic Cell Line, HepG-2 in vitro (Part VI): Acute Biocompatibility Studies
title_short	Effects of Fluorescent Diamond Particles FDP-NV-800nm on Essential Biochemical Functions of Primary Human Umbilical Vein Cells and Human Hepatic Cell Line, HepG-2 in vitro (Part VI): Acute Biocompatibility Studies
title_full	Effects of Fluorescent Diamond Particles FDP-NV-800nm on Essential Biochemical Functions of Primary Human Umbilical Vein Cells and Human Hepatic Cell Line, HepG-2 in vitro (Part VI): Acute Biocompatibility Studies
title_fullStr	Effects of Fluorescent Diamond Particles FDP-NV-800nm on Essential Biochemical Functions of Primary Human Umbilical Vein Cells and Human Hepatic Cell Line, HepG-2 in vitro (Part VI): Acute Biocompatibility Studies
title_full_unstemmed	Effects of Fluorescent Diamond Particles FDP-NV-800nm on Essential Biochemical Functions of Primary Human Umbilical Vein Cells and Human Hepatic Cell Line, HepG-2 in vitro (Part VI): Acute Biocompatibility Studies
title_sort	effects of fluorescent diamond particles fdp-nv-800nm on essential biochemical functions of primary human umbilical vein cells and human hepatic cell line, hepg-2 in vitro (part vi): acute biocompatibility studies
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/3e9fad61d02f4b299f6ce5eb30863791
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Effects of Fluorescent Diamond Particles FDP-NV-800nm on Essential Biochemical Functions of Primary Human Umbilical Vein Cells and Human Hepatic Cell Line, HepG-2 in vitro (Part VI): Acute Biocompatibility Studies

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