Mechanistic Insights into Toxicity of Titanium Dioxide Nanoparticles at the Micro- and Macro-levels

Titanium oxide nanoparticles (TiO₂ NPs) have been regarded as a legacy nanomaterial due to their widespread usage across multiple fields. The TiO₂ NPs have been and are still extensively used as a food and cosmetic additive and in wastewater and sewage treatment, paints, and industrial catalysis as ultrafine TiO₂. Recent developments in nanotechnology have catapulted it into a potent antibacterial and anticancer agent due to its excellent photocatalytic potential that generates substantial amounts of highly reactive oxygen radicals. The method of production, surface modifications, and especially size impact its toxicity in biological systems. The anatase form of TiO₂ (<30 nm) has been found to exert better and more potent cytotoxicity in bacteria as well as cancer cells than other forms. However, owing to the very small size, anatase particles are able to penetrate deep tissue easily; hence, they have also been implicated in inflammatory reactions and even as a potent oncogenic substance. Additionally, TiO₂ NPs have been investigated to assess their toxicity to large-scale ecosystems owing to their excellent reactive oxygen species (ROS)-generating potential compounded with widespread usage over decades. This review discusses in detail the mechanisms by which TiO₂ NPs induce toxic effects on microorganisms, including bacteria and fungi, as well as in cancer cells. It also attempts to shed light on how and why it is so prevalent in our lives and by what mechanisms it could potentially affect the environment on a larger scale.