Objective: Postoperative radiotherapy and/or chemotherapy are still the routine treatment for glioma, however, one of the problems that need to be solved urgently is that the tumor cells in the residual lesion are insensitivity to radiotherapy ^[1-3]. In this work, a stable nano-system was engineered to overcome the insensitive glioma for radiotherapy to a certain degree and enhances magnetic resonance imaging for monitor the radiotherapy at the same time. Result: In this work, we design the MnO₂/Pt system to enhance the radiosensitization from the aspects of improving hypoxia situation and the strong X-ray or gamma-ray attenuation capability of high-Z materials ^[4,5]. The synthesis completely reacted needs to reduce potassium permanganate (KMnO₄) to manganese dioxide (MnO₂) nanosheets in 10 minutes and fix platinum on nanosheets to form the MnO₂/Pt (Mn/Pt =12.5:1) (fig 1.A). As shown in TEM imaging (fig B1-B3), About 1-2 nm of platinum are uniformly dispersed on the nanosheet. At the same time, using the response properties of the tumor microenvironment, such as H₂O₂ are overproduced in cancer cell, and overexpressed glutathione (GSH) in tumor cell, the As-prepared inorganic nanoparticles MnO₂/Pt are degraded into magnetic resonance functional imaging materials Mn²⁺(fig 1.C3) by Fenton-like reaction under the condition of H₂O₂(fig 1.C1-C2). Moreover, for the response of glutathione. Similarly, MnO₂/Pt can degrade GSH to produce Mn²⁺ and oxidized glutathione (GSSG) under different pH conditions (fig 2A). GSSG is not conducive to DNA repair of cancer cells after radiotherapy treatment, which is helpful to the improvement of radiotherapy effect ^[6]. From the colony formation of U87 cells received various Mn treatments indicated treated with 8 Gy, we can preliminarily conclude that the MnO₂/Pt can significantly improve the radiotherapy effect (U87 glioma cells in vitro) compared with the radiotherapy only group and the MnO₂ group (fig 2.C). Both biochemical reactions with MnO2/Pt can produced Mn²⁺ which enhances magnetic resonance imaging. (fig 1.C3 and fig 2.A)This intelligent feature is expected to more accurately evaluate the efficacy of radiotherapy after glioma surgery while sensitizing radiotherapy and to achieve integrated magnetic resonance guided sensitization radiotherapy in vivo.

Acknowledgements

This research was supported by the National Key R&D Program of China (2017YFE0103600), National Natural Science Foundation of China (81720108021, 81601466), and Zhongyuan Thousand Talents Plan Project-- Basic Research Leader Talent (ZYQR201810117)