The aerobic metabolism process of organisms is often accompanied with the production and consumption of reactive oxygen species (ROS), and it plays a very important role in cell signal transduction and maintaining body homeostasis. The increase in ROS levels can cause many pathological dysfunctions, like cancer, which is one of the diseases that seriously threaten human health and leads to an important challenge that humans are facing with. In cancer cells, the increase of ROS level can activate the endogenous cellular antioxidant defense mechanism, leading to the up-regulation of antioxidants and the transformation of redox kinetics from the conventional redox steady state to a new one with high ROS generation-elimination rate, thereby keeping the total ROS level below the toxicity threshold to avoid cell death that is caused by severe oxidative stress. Therefore, it is a feasible cancer treatment strategy to eliminate this adaptive endogenous redox balance through exogenous intervention, which dramatically increases ROS level beyond the cell tolerance threshold. As one of the most typical semiconductor materials, titanium dioxide (TiO2) has unique catalytic property, excellent chemical stability and low biological toxicity. In the excited state, the generated electrons and holes immigrate to the surface, undergoing oxidation-reduction reaction with molecules in the environment (such as H2O, O2) to produce excessive ROS. This will cause severe oxidative stress in cancer cells and consequential apoptosis. Hence, the applications of TiO2 in cancer dynamic therapy attract widespread concern among scientists. However, pure TiO2 nanomaterial has its inherent shortcomings, such as necessity of the high-energy excitation source, low quantum efficiency, poor dispersion in the body, leading to a poor treatment effect of TiO2 in cancer dynamic therapy as well as an obstacle in its clinical transformation. Owing to the large specific surface area and abundant binding sites of TiO2 nanomaterials, it is a feasible strategy to solve the above issues through functionality combination via physical adsorption or chemical binding force. Nano-platforms with multifunctional synergistic effects can make up for the deficiencies of TiO2 itself in terms of structure or functionality, and provide synergistic enhancement or multi-modal treatment of cancer. In this review, starting from the deficiencies of TiO2 nanomaterials in different cancer dynamic therapy methods, different strategies to improve TiO2 nanomaterials through the combination of functional groups are discussed. The applications of TiO2 in the ROS-based therapy, including photodynamic therapy, sonodynamic therapy, radiodynamic therapy, microdynamic therapy etc. are reviewed. In brief, firstly, to solve the limited penetration of ultra violet during the photodynamic therapy of TiO2 nanomaterials, both combination with upconverting nanoparticles and reconstruct the surface through structural engineering will endow TiO2 nanomaterials with absorptivity in biological transparent window. Secondly, apart from combination with noble metal or conductive materials, oxygen-deficient structure will also promote the electron-hole separation and enhance the efficiency of ROS generation during sonodynamic therapy. Thirdly, to reduce the cytotoxicity caused by excess ionizing radiation, combination with other materials to regulate the micro-environment in tumors, enhance the targeting ability, or enhance the ROS generation through interfacial coupling will achieve the radiation dynamic therapy with “1+1>2” effect. Fourthly, microdynamic therapy is a new approach where TiO2 nanomaterials generate ROS through bubble-plasma effect to active oxidative stress in cancer cells. Lastly, TiO2-based sensitizers for cancer dynamic therapy and environmentally responsive drug delivery vehicles have potential applications in cancer treatment. In-depth and systematic research on them is expected to lay the foundation for the development of new anti-tumor nano-platform, but there is still a long way to go.
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Jan 26, 2022
Juan Yang + 19
Open Access