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X-Ray-triggered Carbon Monoxide and Manganese Dioxide Generation based on Scintillating Nanoparticles for Cascade Cancer Radiosensitization |
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| Authors: | Dr Zhen Du Dr Xin Wang Dr Xiao Zhang Dr Zhanjun Gu Dr Xiaoyi Fu Dr Shaoju Gan Dr Ting Fu Dr Sitao Xie Prof Dr Weihong Tan |
| Institution: | 1. The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, 310022 Hangzhou, Zhejiang, China;2. College of Biological Sciences and Biotechnology, Beijing Forestry University, 100083 Beijing, China
These authors contributed equally to this work.;3. Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Institute of Pathology and Southwest Cancer Center, The First Affiliated Hospital, Third Military Medical University, Army Medical University), 40038 Chongqing, China;4. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, 100049 Beijing, China;5. The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, 310022 Hangzhou, Zhejiang, China Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, 410082 Changsha, Hunan, China Institute of Molecular Medicine (IMM), Renji Hospital, School of Medicine, College of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 200240 Shanghai, China |
| Abstract: | Carbon monoxide (CO) is an endogenous signaling molecule with broad therapeutic effects. Here, a multifunctional X-ray-triggered carbon monoxide (CO) and manganese dioxide (MnO2) generation nanoplatform based on metal carbonyl and scintillating nanoparticles (SCNPs) is reported. Attributed to the radioluminescent characteristic of SCNPs, UV-responsive Mn2(CO)10 is not only indirectly activated to release CO by X-ray but can also be degraded into MnO2. A high dose of CO can be used as a glycolytic inhibitor for tumor suppression; it will also sensitize tumor cells to radiotherapy. Meanwhile MnO2, as the photolytic byproduct of Mn2(CO)10, has both glutathione (GSH) depletion and Fenton-like Mn2+ delivery properties to produce highly toxic hydroxyl radical (⋅OH) in tumors. Thus, this strategy can realize X-ray-activated CO release, GSH depletion, and ⋅OH generation for cascade cancer radiosensitization. Furthermore, X-ray-activated Mn2+ in vivo demonstrates an MRI contrast effect, making it a potential theranostic nanoplatform. |
| Keywords: | Carbon Monoxide (CO) Fenton-Like Reaction Glycolysis Radiotherapy Scintillating Nanoparticles (SCNPs) |