ABSTRACT
It is vital to remove residual tumor cells after resection to avoid the recurrence and metastasis of osteosarcoma. In this study, a mineral nanomedicine, europium-doped calcium fluoride (CaF2:Eu) nanoparticles (NPs), is developed to enhance the efficacy of adjuvant radiotherapy (i.e., surgical resection followed by radiotherapy) for tumor cell growth and metastasis of osteosarcoma. In vitro studies show that CaF2:Eu NPs (200 µg/mL) exert osteosarcoma cell (143B)-selective toxicity and migration-inhibiting effects at a Eu dopant amount of 2.95 atomic weight percentage. These effects are further enhanced under X-ray irradiation (6 MeV, 4 Gy). Furthermore, in vivo tests show that intraosseous injection of CaF2:Eu NPs and X-ray irradiation have satisfactory therapeutic efficacy in controlling primary tumor size and inhibiting primary tumor metastasis. Overall, our results suggest that CaF2:Eu NPs with their osteosarcoma cell (143B)-selective toxicity and migration-inhibiting effects combined with radiotherapy might be nanomedicines for treating osteosarcoma after tumor resection.
Subject(s)
Antineoplastic Agents/therapeutic use , Calcium Fluoride/therapeutic use , Europium/therapeutic use , Metal Nanoparticles/therapeutic use , Osteosarcoma/drug therapy , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/toxicity , Calcium Fluoride/chemistry , Calcium Fluoride/toxicity , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Combined Modality Therapy , Europium/chemistry , Europium/toxicity , G2 Phase Cell Cycle Checkpoints/drug effects , Humans , Metal Nanoparticles/chemistry , Metal Nanoparticles/toxicity , Mice , Radiotherapy, AdjuvantABSTRACT
INTRODUCTION: The purpose of this in vitro study was to compare the cytotoxicity of white mineral trioxide aggregate cement (AMTA, MTA-Angelus), Brasseler Endosequence Root Repair Putty (ERRM), Dycal, and Ultra-blend Plus (UBP) by using human dermal fibroblasts and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. METHODS: Cultured adult human dermal fibroblasts were exposed to multiple concentrations of material elutes. The test material samples were immersed and incubated in the culture medium for 2, 5, or 8 days at 37°C. The cytotoxic effects were recorded by using an MTT-based colorimetric assay. Positive and negative controls were used. The results were statistically examined by one-way analysis of variance and Tukey post tests. RESULTS: The cell viability of cultures exposed to all dilutions of AMTA, ERRM, and UBP was statistically similar to the negative control at 2 and 5 days. Only the Dycal-exposed specimens exhibited a statistically significant increase in cytotoxicity at the 2 initial evaluation periods. After exposure to the 8-day elutes, the respective percentage of cell survivability was 91% (Brasseler), 88% (MTA-Angelus), 76% (Ultra-blend Plus), and 37% (Dycal). CONCLUSIONS: From the data in this in vitro study, AMTA, ERRM, and UBP had statistically similar adult human dermal fibroblast cytotoxicity levels. Relative to the negative control, only Dycal was shown to have a statistically significant cytotoxic effect to adult human dermal fibroblasts at all tested intervals.
Subject(s)
Calcium Phosphates/toxicity , Oxides/toxicity , Pulp Capping and Pulpectomy Agents/toxicity , Silicates/toxicity , Tantalum/toxicity , Zirconium/toxicity , Adult , Calcium Fluoride/toxicity , Calcium Hydroxide/toxicity , Cell Culture Techniques , Cell Line , Cell Survival/drug effects , Colorimetry/methods , Coloring Agents , Culture Media, Conditioned , Drug Combinations , Fibroblasts/drug effects , Humans , Minerals/toxicity , Organic Chemicals/toxicity , Skin/cytology , Skin/drug effects , Temperature , Tetrazolium Salts , Thiazoles , Time FactorsABSTRACT
An animal model of chronic fluorosis was produced by subjecting Wistar rats to high doses of fluoride in drinking water for a prolonged period. Phospholipid and neutral lipid contents in rat kidney were then analyzed by high-performance liquid chromatography (HPLC), and fatty acid compositions from individual phospholipids were measured by gas chromatography. Lipid peroxidation was detected by the thiobarbituric-acid-reactive substance assay. Results showed that the total phospholipid content significantly decreased in the kidney of the rats treated with high doses of fluoride and the main species influenced were phosphatidylethanolamine (PE) and phosphatidylcholine (PC). Decreased proportions of polyunsaturated fatty acids were observed in PE and PC in kidney of fluoride-treated animals compared to controls. No changes could be detected in the amounts of cholesterol and dolichol in kidneys between the rats treated with fluoride and controls. A significant decrease of ubiquinone in rat kidney was observed in the groups treated with excessive fluoride. High levels of lipid peroxidation were detected in kidney of the rats with fluorosis. It is plausible that the specific modification of lipid composition results from lipid peroxidation. The oxidative stress and modification of cellular membrane lipids may be involved in the pathogenesis of chronic fluorosis and provide a possible explanation for the gross system damage observed in the body, especially in soft tissues and organs.
Subject(s)
Fluoride Poisoning/metabolism , Kidney/metabolism , Membrane Lipids/metabolism , Animals , Calcium Fluoride/pharmacokinetics , Calcium Fluoride/toxicity , Cholesterol/analysis , Chromatography, High Pressure Liquid , Disease Models, Animal , Dolichols/analysis , Fatty Acids, Unsaturated/analysis , Female , Intracellular Membranes/drug effects , Intracellular Membranes/metabolism , Kidney/drug effects , Lipid Peroxidation/drug effects , Male , Phosphatidylcholines/analysis , Phosphatidylethanolamines/analysis , Rats , Rats, Wistar , Ubiquinone/analysis , Water SupplyABSTRACT
A comparison of the toxicity of SnF2, BaF2, KF, CaF2, and MgF2 shows that the hard-to-dissolve fluorides CaF2 and MgF2 are absolutely safe. The other fluorides tested showed no toxic effects in dosages relevant for caries prophylaxis and with oral application.
