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Title: On-demand generation of peroxynitrite from an integrated two-dimensional system for enhanced tumor therapy
Authors: Liu, Shikai
Li, Wenting
Chen, Hengxing
Zhou, Jialing
Dong, Shuming
Zang, Pengyu
Tian, Boshi
Ding, He
Gai, Shili
Yang, Piaoping
Zhao, Yanli
Keywords: Science::Chemistry
Issue Date: 2022
Source: Liu, S., Li, W., Chen, H., Zhou, J., Dong, S., Zang, P., Tian, B., Ding, H., Gai, S., Yang, P. & Zhao, Y. (2022). On-demand generation of peroxynitrite from an integrated two-dimensional system for enhanced tumor therapy. ACS Nano, 16(6), 8939-8953.
Project: A20E5c0081 
Journal: ACS Nano 
Abstract: Nanosystem-mediated tumor radiosensitization strategy combining the features of X-ray with infinite penetration depth and high atomic number elements shows considerable application potential in clinical cancer therapy. However, it is difficult to achieve satisfactory anticancer efficacy using clinical radiotherapy for the majority of solid tumors due to the restrictions brought about by the tumor hypoxia, insufficient DNA damage, and rapid DNA repair during and after treatment. Inspired by the complementary advantages of nitric oxide (NO) and X-ray-induced photodynamic therapy, we herein report a two-dimensional nanoplatform by the integration of the NO donor-modified LiYF4:Ce scintillator and graphitic carbon nitride nanosheets for on-demand generation of highly cytotoxic peroxynitrite (ONOO–). By simply adjusting the Ce3+ doping content, the obtained nanoscintillator can realize high radioluminescence, activating photosensitive materials to simultaneously generate NO and superoxide radical for the formation of ONOO– in the tumor. Obtained ONOO– effectively amplifies therapeutic efficacy of radiotherapy by directly inducing mitochondrial and DNA damage, overcoming hypoxia-associated radiation resistance. The level of glutamine synthetase (GS) is downregulated by ONOO–, and the inhibition of GS delays DNA damage repair, further enhancing radiosensitivity. This work establishes a combinatorial strategy of ONOO– to overcome the major limitations of radiotherapy and provides insightful guidance to clinical radiotherapy.
ISSN: 1936-0851
DOI: 10.1021/acsnano.1c11422
Schools: School of Physical and Mathematical Sciences 
School of Chemistry, Chemical Engineering and Biotechnology 
Rights: This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Nano, copyright © 2022 American Chemical Society, after peer review and technical editing by the publisher. To access the final edited and published work see
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:CCEB Journal Articles
SPMS Journal Articles

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