Silica nanoparticles (SiNPs) are the general name for nanomaterials composed of silicon dioxide (SiO2), which commonly occurs in crystalline and amorphous forms. The term ‘SiNPs’ refers to silicon dioxide materials with particles smaller than 100 nm, while subsequent research has proposed that the definition of nanomaterials should encompass particles with surfaces larger than 60 m2/cm3. (Kreyling et al., 2010; Napierska et al., 2010). The crystalline form of silica particles has been identified as a major risk factor of silicosis and a group I carcinogenic compound to humans by the International Agency for Research on Cancer (IARC), whereas the impact of amorphous form on the human body has not been confirmed (Leung et al., 2012; Murugadoss et al., 2017). As nanomaterials, synthetic amorphous SiNPs have unique properties, such as favorable biocompatibility, biodegradability, high stability, adjustability, and mechanical strength (Mebert et al., 2017). With these desirable physical and chemical properties, amorphous SiNPs have been extensively used in pest control, food additives, cosmetics, and drug delivery (Lee et al., 2017; Li et al., 2019c; Morais et al., 2022; Thabet et al., 2021). The mass production and application strongly increased the release of SiNPs into the environment, which eventually resulted in exposure to humans, especially in occupational circumstances (Kim et al., 2014). WHO has highlighted that the potential risk of nanomaterials to workers in all countries via occupational exposure. According to published WHO guidelines in 2017, synthetic amorphous SiNPs have been recognized as the second-largest nanomaterials produced in the world, with an annual production of 1.5 million tons (WHO, 2017). It was also estimated that the application of SiNPs increased by 5.6% annually, and their projected market reached $8.8 billion in 2020 (Nayl et al., 2022; Nguyen et al., 2019b).

Considering their potential toxicity, institutions have set up specific toxicity assessment programs for SiNPs. The National Institute of Environmental Health Sciences (NIEHS) and the American Recovery and Reinvestment Act (ARRA) have supported mounting studies to reveal the potential impacts of nanomaterials on human health, many of which have identified the health effects of SiNPs (NIEHS, 2023). Since nanomaterials like SiNPs have been extensively used in the cosmetic industry, The U.S. Food and Drug Administration (FDA) issued guidelines in 2014 to facilitate the safety evaluation of nanomaterials in cosmetic products (FDA, 2014). To address these issues, the National Center for Toxicological Research (NCTR) is also focusing on detecting and identifying nanomaterials in FDA-regulated products and conducting numerous studies to reveal their potential toxicity (NCTR, 2021). In recent years, mounting studies have reported the toxicity of SiNPs, especially amorphous SiNPs (Ryu et al., 2014). SiNPs have been reported to induce toxic effects on a variety of organisms including algae, bacteria, unicellular organisms, crustaceans, fish, and mollusks (Book and Backhaus, 2022). Studies also suggested that SiNPs may enter the human body through a variety of routes, mainly including inhalation, oral intake, and transdermal absorption (Arriagada and Morales, 2019; Boccuni et al., 2020; Brand et al., 2021). Indeed, SiNPs have been reported to induce adverse effects on respiratory, cardiovascular, intestinal, hepatic, immune, and reproductive systems in model organisms and cultured cell lines (Chen et al., 2018; Deng et al., 2021; Guo et al., 2021; Nishimori et al., 2009; Wang et al., 2020b; Zhang et al., 2020b). Nevertheless, mesoporous SiNPs with a controllable pore volume were also considered desirable assistance for biotherapeutic delivery and bioimaging, as well as the favorable materials that contributed to tissue regeneration (Wang et al., 2015). Therefore, the line between the biomedical application of SiNPs and their toxicity remains blurred.

This review will detail the application of SiNPs and their potential release routes into the environment, thus discussing the existing benefits of SiNPs and the possibility of exposure to humans. This will follow a summary of SiNPs-related toxic effects on various model organisms. Finally, the potential toxicity and underlying mechanisms of SiNPs will be elucidated based on the existing evidence obtained from both in vivo and in vitro trials. Taken together, this review details the application of SiNPs in multiple fields, reviewing SiNPs-related biological impacts, and eventually building up a panorama that links the use of SiNPs to the consequent biological effects and essential mechanisms. Therefore, this review is in favor of improving the understanding of the current assessment of environmental and toxicological effects of SiNPs, identifying the gaps in these studies, as well as providing a novel perspective of the differentiation between the application and hazard of SiNPs.