TME-Activated MnO2/Pt Nanoplatform of Hydroxyl Radical and Oxygen Generation to Synergistically Promote Radiotherapy and MR Imaging of Glioblastoma
Lijuan Chen, Mingbo Liu, Yunjuan Wang, Weiwei Fu, Yaqiong Li, Yan Bai, Xuan Yu, Lei Jiao, Meiyun Wang
Abstract
Purpose: Radiotherapy (RT) is currently recognized as an important treatment for glioblastoma (GBM), however, it is associated with several challenges. One of these challenges is the radioresistance caused by hypoxia, whereas the other is the low conversion efficiency of the strongly oxidized hydroxyl radical (•OH), which is produced by the decomposition of water due to high-energy X-ray radiation. These factors significantly limit the clinical effectiveness of radiotherapy. Results: To address these limitations, we developed a highly stable and efficient nanoplatform (MnO 2 /Pt@BSA). Compared to MnO 2 @BSA, this platform demonstrates high stability, a high yield of oxygen (O 2 ), enhanced production of •OH, and reduced clearance of •OH. The system exhibited increased O 2 production in vitro and significantly improved oxygen production efficiency within 100 s at the Pt loading of 38.7%. Furthermore, compared with MnO 2 , the expression rate of hypoxia-inducible factor (HIF-1α) in glioma cells treated with MnO 2 /Pt decreased by half. Additionally, the system promotes •OH generation and consumes glutathione (GSH), thereby inhibiting the clearance of •OH and enhancing its therapeutic effect. Moreover, the degradation of the nanoplatform produces Mn 2+ , which serves as a magnetic resonance imaging (MRI) contrast agent with a T 1 -weighted enhancement effect at the tumor site. The nanoplatform exhibited excellent biocompatibility and performed multiple functions related to radiotherapy, with simpler components. In U87 tumor bearing mice model, we utilized MnO 2 /Pt nanocatalysis to enhance the therapeutic effect of radiotherapy on GBM. Conclusion: This approach represents a novel and effective strategy for enhancing radiotherapy in gliomas, thereby advancing the field of catalytic radiotherapy and glioma treatment. Keywords: radiotherapy, glioblastoma, MnO 2 /Pt@BSA nanoplatform, nanocatalysis