Synthetic amorphous silica nanoparticles: toxicity, biomedical and environmental implications

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. Synthetic amorphous silica nanoparticles are produced in tonnage quantities for a range of commercial uses. In this Review, the synthesis-structure-property relationships of synthetic amorphous silica nanoparticles are outlined, with an emphasis on biomedical applications and environmental implications.