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Published on: June 21, 2015
Toxicity Patterns of Clinically Relevant Metal Oxide Nanoparticles
Anna F Fakhardo1, Elizaveta I Anastasova1, Sabina R Gabdullina1
1Laboratory of Solution Chemistry of Advanced Materials and Technology, ITMO University, St. Petersburg 197101, Russia.
Abstract:
Nanostructured drugs are being approved for clinical use, although there is a serious deficit of systematic studies of these materials. Data on toxicity of nanoparticles (NPs) can vary due to different methods of preparation, size, and shape. We investigated the toxicity against cultured human cells, the acute toxicity in mice, and the influence on conjugative transfer of antibiotic resistance genes of clinically relevant NPs such as TiO2, ZrO2, HfO2, Ta2O5, Fe3O4, and AlOOH. NPs were synthesized as aqueous sols by the same method in aqueous solution, with almost identical size 2-10 nm. None of these NPs was cytotoxic at concentrations compatible with water solubility. Furthermore, TiO2, HfO2, Ta2O5, Fe3O4, and AlOOH were not toxic to mice after oral administration. However, ZrO2 showed rather high toxicity, with LD50 2277.8 mg/kg. Experiments with plasmid transfer between bacteria demonstrated that AlOOH NPs were the most hazardous since this material promoted the emergence of resistance to antibiotics. Thus, although our metal oxide NPs are largely non-toxic, their properties may differ in specific biological situations.
Insights
Clinically relevant nanoparticles (NPs) showed low toxicity in cell cultures and mice. However, aluminum oxyhydroxide (AlOOH) NPs promoted antibiotic resistance gene transfer, highlighting potential risks.
Area of Science:
- Materials Science
- Toxicology
- Nanotechnology
Background:
- Nanostructured drugs are increasingly approved, but systematic toxicity studies are lacking.
- Nanoparticle (NP) toxicity data varies significantly based on preparation, size, and shape.
- Understanding the biological impact of clinically relevant NPs is crucial.
Purpose of the Study:
- To systematically investigate the toxicity of various metal oxide nanoparticles (NPs).
- To assess cytotoxicity, acute toxicity in mice, and effects on antibiotic resistance gene transfer.
- To evaluate the safety of TiO2, ZrO2, HfO2, Ta2O5, Fe3O4, and AlOOH NPs.
Main Methods:
- Synthesized NPs (2-10 nm) as aqueous sols using a standardized method.
- Assessed cytotoxicity in cultured human cells at water-solubility-compatible concentrations.
- Determined acute oral toxicity in mice (LD50) and evaluated plasmid transfer between bacteria.
Main Results:
- No NP tested was cytotoxic to human cells at relevant concentrations.
- TiO2, HfO2, Ta2O5, Fe3O4, and AlOOH NPs showed no acute toxicity in mice upon oral administration.
- ZrO2 NPs exhibited significant toxicity (LD50 = 2277.8 mg/kg).
- AlOOH NPs were most hazardous, promoting antibiotic resistance gene transfer.
Conclusions:
- Most investigated metal oxide NPs demonstrate low toxicity in vitro and in vivo.
- ZrO2 NPs present a notable toxicity risk.
- AlOOH NPs pose a significant risk due to their ability to promote antibiotic resistance.
- The biological impact of NPs can be context-dependent, necessitating further investigation.
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