scholarly journals MTH1 inhibitor amplifies the lethality of reactive oxygen species to tumor in photodynamic therapy

2020 ◽  
Vol 6 (10) ◽  
pp. eaaz0575 ◽  
Author(s):  
Lingzhi Zhao ◽  
Junyao Li ◽  
Yaoquan Su ◽  
Liqiang Yang ◽  
Liu Chen ◽  
...  

Although photodynamic therapy (PDT) has been clinically applied tumor hypoxia still greatly restricts the performance of this oxygen-dependent oncological treatment. The delivery of oxygen donors to tumor may produce excessive reactive oxygen species (ROS) and damage the peripheral tissues. Herein, we developed a strategy to solve the hypoxia issue by enhancing the lethality of ROS. Before PDT, the ROS-defensing system of the cancer cells was obstructed by an inhibitor to MTH1, which is a key for the remediation of ROS-caused DNA damage. As a result, both nuclei and mitochondrial DNA damages were increased, remarkably promoting cellular apoptosis. The therapeutic results demonstrated that the performance of PDT can be improved by the MTH1 inhibitor, leading to efficient cancer cell killing effect in the hypoxic tumor. This strategy makes better use of the limited oxygen, holding the promise to achieve satisfactory therapeutic effect by PDT without generating redundant cytotoxic ROS.

2019 ◽  
Vol 20 (5) ◽  
pp. 1148 ◽  
Author(s):  
Chun-Chen Yang ◽  
Wei-Yun Wang ◽  
Feng-Huei Lin ◽  
Chun-Han Hou

Conventional photodynamic therapy (PDT) is limited by its penetration depth due to the photosensitizer and light source. In this study, we developed X-ray induced photodynamic therapy that applied X-ray as the light source to activate Ce-doped CaCO3 (CaCO3:Ce) to generate an intracellular reactive oxygen species (ROS) for killing cancer cells. The A549 cell line was used as the in vitro and in vivo model to evaluate the efficacy of X-ray-induced CaCO3:Ce. The cell viability significantly decreased and cell cytotoxicity obviously increased with CaCO3:Ce exposure under X-ray irradiation, which is less harmful than radiotherapy in tumor treatment. CaCO3:Ce produced significant ROS under X-ray irradiation and promoted A549 cancer cell death. CaCO3:Ce can enhance the efficacy of X-ray induced PDT, and tumor growth was inhibited in vivo. The blood analysis and hematoxylin and eosin stain (H&E) stain fully supported the safety of the treatment. The mechanisms underlying ROS and CO2 generation by CaCO3:Ce activated by X-ray irradiation to induce cell toxicity, thereby inhibiting tumor growth, is discussed. These findings and advances are of great importance in providing a novel therapeutic approach as an alternative tumor treatment.


2020 ◽  
Vol 96 (2) ◽  
pp. 340-348 ◽  
Author(s):  
Yi Hong Ong ◽  
Andreaa Dimofte ◽  
Michele M. Kim ◽  
Jarod C. Finlay ◽  
Tianqi Sheng ◽  
...  

2019 ◽  
Vol 7 (46) ◽  
pp. 7306-7313 ◽  
Author(s):  
Jinhua Wu ◽  
Shanshan Du ◽  
Yuhua Wang

Rare-earth-based upconversion nanotechnology has recently shown great promise for photodynamic therapy (PDT).


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