Synthetic amorphous silica nanoparticles: toxicity, biomedical and environmental implications

Abstract

Natural silica and silicates are predominantly crystalline and constitute the most abundant components of the Earth’s crust. Man-made silica is typically amorphous and manufactured in tonnage quantities for commercial use and, more recently, for burgeoning medical applications, making synthetic amorphous silica nanoparticles (SASNs) arguably the most abundant nanoparticles on Earth. Despite the abundance of silica and SASNs, misconceptions remain regarding what silica is and its medical and environmental implications. SASNs are often considered to be toxic regardless of their source, but, here, we emphasize that all silica nanoparticles are not created equal and explore how composition, synthesis, processing and environmental exposure effect toxicity. Despite having comparable size, shape and nominal composition, SASNs prepared by pyrolytic or colloidal processes can have drastically different toxicities, which, to date, is not generally recognized by the research community. In this Review, we begin with a survey of relationships between synthetic methods and material structure, followed by structure–toxicity relationships. Next, we explore the environmental implications of SASNs exposure and provide a review of the emerging biomedical uses of SASNs in therapy, imaging and theranostics. We conclude with our vision for the field and suggest that minimal SASN characterization standards are needed for reporting and understanding their biological or environmental behaviours and implications.

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Fig. 1: The framework and surface chemistry of amorphous and crystalline silica.
Fig. 2: Timeline of the development and taxonomy of synthetic amorphous silica nanoparticles.
Fig. 3: Synthesis–structure–biosafety relationships of fumed and colloidal silicas.
Fig. 4: Representative data sets of physicochemical determinants of the toxicity of synthetic amorphous silica nanoparticles.
Fig. 5: Cell viability and haemolytic behaviour of various silica nanoparticles.
Fig. 6: Intracellular fate of silica nanoparticles.
Fig. 7: Select surface modifications of synthetic amorphous silica nanoparticles and their functions.
Fig. 8: Schematic of in vivo toxicology testing.
Fig. 9: Relationships between the six main sources of silica on Earth.
Fig. 10: A schematic of the modular features of mesoporous silica and silsesquioxane-based delivery platforms.
Fig. 11: A selection of mesoporous silica supramolecular nanovalves and nanomachines developed to achieve stimulus-triggered release of cargo.

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Acknowledgements

This work was supported in part by the U.S. National Institutes of Health under contract number 1 R01 CA226537-01. K.S.B. acknowledges support by the Laboratory Directed Research & Development program at Sandia National Laboratories. Sandia National Laboratories is a multi-mission laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC, a wholly owned subsidiary of Honeywell International, Inc., for the U.S. Department of Energy National Nuclear Security Administration under contract DE-NA-0003525. Any subjective views or opinions that might be expressed in the paper do not necessarily represent the views of the U.S. Department of Energy or the U.S. Government.

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C.J.B. contributed to the writing and revision of the manuscript. J.G.C. contributed to the literature research, writing of the manuscript and the design of the display items. K.S.B. contributed to the literature research, writing and revision of the manuscript. J.I.Z. contributed to the writing and revision of the manuscript.

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Correspondence to C. Jeffrey Brinker.

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Croissant, J.G., Butler, K.S., Zink, J.I. et al. Synthetic amorphous silica nanoparticles: toxicity, biomedical and environmental implications. Nat Rev Mater (2020). https://doi.org/10.1038/s41578-020-0230-0

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