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 concentration...

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Bibliographic Details
Published in:ACS omega 2022-05, Vol.7 (21), p.17563-17574
Main Authors: Robeldo, Thaiane, Ribeiro, Lucas S., Manrique, Lida, Kubo, Andressa Mayumi, Longo, Elson, Camargo, Emerson Rodrigues, Borra, Ricardo Carneiro
Format: Article
Language:English
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Summary: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.
ISSN:2470-1343
2470-1343
DOI:10.1021/acsomega.1c07046