MnO2 nanozyme with lanthanide-based radiosensitization for advanced radiotherapy by tumor microenvironment triggering STING pathway activation

Tan，Meiling1; Gao，Zhimin1; Wang，Xiaozhao1; Lin，Chen1; Wan，Yuchi1; Xie，Wenyu1; Chen，Wei1; Zhang，Yaru1; Quan，Zewei2; Hou，Zhiyao1

2024-04-15

10.1016/j.cej.2024.150364

Chemical Engineering Journal   影响因子和分区

1385-8947

Radiotherapy, being a primary approach for cancer treatment, is plagued by systemic toxicity resulting from high-dose radiation, as well as radioresistance due to the unique characteristics of tumor microenvironment (TME), including hypoxia, high expression of reducing substances and immunosuppression. The collaboration between radiosensitization and manipulation of the TME has the potential to surmount the challenges associated with advanced radiotherapy. Here, we propose a radiosensitization approach that involves enhancing X-ray deposition through physical means, while simultaneously reducing radioresistance and activating the stimulator of interferon genes (STING) pathway using a nanozyme that mimics natural enzymatic activity. This is achieved by fabricating a lanthanide ion radiosensitizer-based multifunctional enzyme activity nanoplatform, MnO@NaGdF:5%Nd@NaYbF:20%Nd(MN). In the TME, the NaGdF:5%Nd@NaYbF:20%Nd radiosensitizer sensitizes cancer cells to X-ray. The MnO exhibits catalase-like (CAT) activity, enabling it to catalyze the conversion of HO into O, thereby alleviating tumor hypoxia. Additionally, MnO reacts with overexpressed glutathione (GSH) by glutathione oxidase-like (GSHOx) activity to generate Mn ions. This reaction optimizes the function of ·OH, which can also be produced by the released Mn through a Fenton-like reaction. The DNA damage caused by ·OH can be detected by cyclic GMP-AMP synthase (cGAS) to activate STING pathway, which also can be activated by the released Mn ion. Through a two-pronged strategy with radical oxygen species overproduction and STING pathway activation, the lanthanide doped radiosensitizer-based MN can be relied upon to deliver highly effective radiotherapy.

Lanthanide doped sensitizer Manganese oxide nanozyme Radiosensitization Stimulator of interferon genes

SCI ; EI

英语

通讯

ENGINEERING

2-s2.0-85187958960

Scopus

1.Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation,School of Basic Medical Sciences,Guangzhou Medical University,Guangzhou,511436,China
2.Department of Chemistry,Southern University of Science and Technology (SUSTech),Shenzhen,Guangdong,518055,China

Tan，Meiling,Gao，Zhimin,Wang，Xiaozhao,et al. MnO2 nanozyme with lanthanide-based radiosensitization for advanced radiotherapy by tumor microenvironment triggering STING pathway activation[J]. Chemical Engineering Journal,2024,486.

Tan，Meiling.,Gao，Zhimin.,Wang，Xiaozhao.,Lin，Chen.,Wan，Yuchi.,...&Hou，Zhiyao.(2024).MnO2 nanozyme with lanthanide-based radiosensitization for advanced radiotherapy by tumor microenvironment triggering STING pathway activation.Chemical Engineering Journal,486.

Tan，Meiling,et al."MnO2 nanozyme with lanthanide-based radiosensitization for advanced radiotherapy by tumor microenvironment triggering STING pathway activation".Chemical Engineering Journal 486(2024).