Modified Titanium Dioxide as a Potential Visible-Light-Activated Photosensitizer for Bladder Cancer Treatment

Low oxygen concentration inside the tumor microenvironment represents a major barrier for photodynamic therapy of many malignant tumors, especially urothelial bladder cancer. In this context, titanium dioxide, which has a low cost and can generate high ROS levels regardless of local O₂ concentrations, could be a potential type of photosensitizer for treating this type of cancer. However, the use of UV can be a major disadvantage, since it promotes breakage of the chemical bonds of the DNA molecule on normal tissues. In the present study, we focused on the cytotoxic activities of a new material (Ti(OH)₄) capable of absorbing visible light and producing high amounts of ROS. We used the malignant bladder cell line MB49 to evaluate the effects of multiple concentrations of Ti(OH)₄ on the cytotoxicity, proliferation, migration, and production of ROS. In addition, the mechanisms of cell death were investigated using FACS, accumulation of lysosomal acid vacuoles, caspase-3 activity, and mitochondrial electrical potential assays. The results showed that exposure of Ti(OH)₄ to visible light stimulates the production of ROS and causes dose-dependent necrosis in tumor cells. Also, Ti(OH)₄ was capable of inhibiting the proliferation and migration of MB49 in low concentrations. An increase in the mitochondrial membrane potential associated with the accumulation of acid lysosomes and low caspase-3 activity suggests that type II cell death could be initiated by autophagic dysfunction mechanisms associated with high ROS production. In conclusion, the characteristics of Ti(OH)₄ make it a potential photosensitizer against bladder cancer.