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

Gerstenhaber, Jonathan A; Marcinkiewicz, Cezary; Barone, Frank C.; Sternberg, Mark; D’Andrea, Michael R.; Lelkes, Peter I.; Feuerstein, Giora

doi:10.2147/ijn.s209663

Cited by 12 publications

(23 citation statements)

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“…into intact rats to establish the pharmacokinetic profile and organ distribution as well as to assess a comprehensive panel of hematologic, metabolic and biochemical safety biomarkers. [18][19][20] In these studies, we found that within the 5 days to 12 weeks follow-up periods, FDP-NV primarily distributed to the liver and spleen, and that virtually none were found in the lung, heart, and kidney. [18][19][20] Furthermore, no specific histopathological observations related to the FDP-NV particles' potential cyto-/histo-toxicity were observed.…”

Section: Introductionmentioning

confidence: 75%

“…[18][19][20] In these studies, we found that within the 5 days to 12 weeks follow-up periods, FDP-NV primarily distributed to the liver and spleen, and that virtually none were found in the lung, heart, and kidney. [18][19][20] Furthermore, no specific histopathological observations related to the FDP-NV particles' potential cyto-/histo-toxicity were observed. However, no study so far addressed possible acute safety or toxicological consequences in endothelial or hepatic parenchyma cells exposed to FDP-NV-800nm.…”

Section: Introductionmentioning

confidence: 75%

“…Cells were maintained a 37°C in 5% CO 2 atmosphere in a humidified incubator in their respective culture media as previously described. 20 HepG-2 and HUVEC were "seeded" in 96-well plates (2 x 10 3 cells per well in 100 μL medium) and allowed to attach and spread by overnight. Some of the wells were fixed with 4% paraformaldehyde (PFA, ThermoFisher Sci.)…”

Section: Cell Counting Assaymentioning

confidence: 99%

“…These cells served as a control for time 0. In separate plates, 20 cells were treated or not for 24 hrs. with FDP-NV.…”

Section: Cell Counting Assaymentioning

confidence: 99%

“…These cells were chosen since endothelial cells are the first line of exposure to FDP-NV, when infused into the systemic circulation (as per the intended clinical indication), while hepatocytes are the primary repository of circulating FDP-NV. 20 HepG-2 cell line is cancer human hepatoma, but it is used as a model for study in vitro of drug metabolism and hepatotoxicity. 21 In presented study, we used HepG-2 cell line to investigate the proliferationrelated activity of FDP-NV, because primary hepatocytes do not proliferate in vitro.…”

Section: Introductionmentioning

confidence: 99%

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<p>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</p>

Marcinkiewicz¹,

Lelkes²,

Sternberg³

et al. 2020

NSA

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Background: 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, C max). 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 FBSstimulated 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 C max levels are very short-living, the risk for endothelial injury is likely minimal for slow rate cell proliferation such as endothelial cells.

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