Titanium dioxide nanoparticles in oncology: synthesis, application, and challenges

Nanoparticles (NPs) are defined as particles that have a diameter less than 100 nm. Titanium dioxide (TiO₂) NPs (TiO₂ NPs) have gained significant attention in recent years as a possible therapeutic agent due to their unique physiochemical properties. They include tunability of the NPs, effective dopant compatibility, biocompatibility and catalytic properties. The shape and size of the NPs also play an important role in TiO₂ NPs for its efficiency in drug encapsulation, circulation time, efficacy and aggregation. The most effective size for TiO₂ NPs ranges from 20-150 nm, with the preferred shape being spherical. TiO₂ NPs, although largely ineffective as the sole therapeutic agent, have shown the ability to reduce tumorigenesis and augment the efficacy of cancer therapy in a range of cancers and treatments, such as photodynamic therapy (PDT), sonodynamic therapy (SDT), photothermal therapy (PTT), immunotherapy, and chemotherapy. However, TiO₂ NPs have been associated with cytotoxic and genotoxic effects in several settings, which are discussed in this review. Regulatory barriers hinder its applicability, and are directly related to long-term toxicity due to prolonged exposure. These obstacles have hindered translation of these NP-based technologies in clinical settings. This highlights the need to conduct further research to address possible concerns regarding toxicity and safety even after long-term exposure. In this review, we discuss the mechanism of TiO₂ NPs as a DDA, its applications in cancer therapy, potential risks, as well as strategies to minimize its associated risks.