Toxicity Assessment of Mesoporous Silica Nanoparticles: Emphasizing Biological Factors in Nano-Bio Interactions

Mesoporous silica nanoparticles (MSNs) are emerging as promising drug delivery systems due to their tunable physicochemical properties. However, concerns regarding their toxicity across different biological environments remain elusive. This review delves into the complex interactions between MSNs and various model systems, examining the resulting toxicological effects. In particular, within the tumor microenvironment, the hyperacidic microenvironment and altered glucose metabolism in cancer cells influence the biological outcomes of MSNs compared to normal cells. The immunomodulatory effects by MSNs, such as macrophages polarization and dendritic cells activation, are discussed. Moreover,in vivo studies using both wild-type and transgenic models highlight species- and organ-specific toxicities, particularly impacting the liver and kidneys. However, the potential epigenetic effects of these altered genes, as well as the characterization of the biotransformation processes of MSNs within various biological microenvironments, remain underexplored. These findings underscore the need for a thorough understanding of nano-bio interactions and the role of biological factors — such as exposure routes and species differences — in assessing MSNs safety. Furthermore, the need to refine model systems to better mimic human physiological conditions and assess the long-term effects of MSNs is underlined. Ultimately, a comprehensive understanding of the structure–activity relationships of MSNs within diverse biological systems is crucial for mitigating risks and minimizing off-target effects in biomedical applications.