机构：[1]Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.四川大学华西医院[2]Sichuan Provincial Key Laboratory of Nuclear Physics and Medical Research, Sichuan University, Chengdu 610041, China.[3]College of Polymer Science and Engineering, State Key Laboratory of Advanced Polymer Materials, Sichuan University, Chengdu 610065, China.[4]Department of Endodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.[5]Institute of Chemistry and Biochemistry, Free University of Berlin, Berlin 14195, Germany.[6]School of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, China.
Reactive oxygen species (ROS)-catalytic therapies have gained increasing popularity in preventing tumor metastasis and recurrence, yet their efficiency is often compromised by limited systemic immune activation. Herein, we report the de novo design of Ru-coordinated bis-Schiff base salphen-covalent organic frameworks (SCOF-Ru) to serve as semiconducting artificial enzymes with radio-activable ROS-catalytic efficiency and antitumor immunity for suppressing tumor metastasis and recurrence. Experimental and theoretical results demonstrate that the semiconducting SCOF-Ru displays large π-conjugation, efficient electron transfer, strong electron-hole separation, and unique Ru2-N4O2 catalytic centers, enabling the most superior ROS production capability under low-dose X-ray irradiation. Rather than relying on high-Z elements, semiconducting SCOF-Ru with optimized band structures endows Ru sites with high radiosensitization effects. Our findings have disclosed that the SCOF-Ru can not only effectively inhibit DNA repair but also trigger robust apoptosis through the downregulation of calcium signaling pathways. Correspondingly, the therapeutic superiority and recurrence inhibition efficacies of SCOF-Ru have been validated in different tumor models, especially radiotherapy-resistant patient-derived xenograft models. Combined with immune checkpoint blockade, radio-activable SCOF-Ru shows great potential to robustly inhibit the growth of distant tumors. We believe the innovative design of ROS-catalytic and radio-activable artificial enzymes will enable a promising avenue for treating malignant tumors.
基金：
This work was financially supported by the National Key
Research and Development Program of China
(2024YFE0201200), the Noncommunicable Chronic Diseases-National Science and Technology Major Project
(2023ZD0503000 and 2023ZD0503004), the Regional Innovation and Development Joint Fund Key Project of the
National Natural Science Foundation of China (U24A20735),
the National Natural Sciences Foundation of China
(82473434, 52525311), Sichuan Provincial Science and
Technology Department Key Research and Development
Program (2022YFSY0012), Sichuan Science and Technology
Program (2025YFHZ0087, 2024YFHZ0041, 2024ZYD0054),
Science and Technology Project of Sichuan Provincial Health
Commission (Clinical Research Special Project JH2023082),
the International Science and Technology Cooperation
Program of Chengdu Science and Technology Bureau (2024-
YF06−00011-HZ and 2022-GH03−00004-HZ), the Health
Research Project of Chengdu Eastern New Area Management
Committee (202304), 1.3.5 project for disciplines of excellence
from West China Hospital of Sichuan University
(ZYYC23006), Clinical Research Incubation Project of West
China Hospital (23HXFH001), Yunnan Province Key
Laboratory of Precision Diagnosis and Treatment for Thoracic
Diseases (202449CE340026) and the Ministry of Education
University-Industry Collaborative Education Program
(230720523707281).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2025]版：
大类|1 区材料科学
小类|1 区化学：综合1 区材料科学：综合1 区纳米科技
最新[2025]版：
大类|1 区材料科学
小类|1 区化学：综合1 区材料科学：综合1 区纳米科技
第一作者：
第一作者机构：[1]Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.[2]Sichuan Provincial Key Laboratory of Nuclear Physics and Medical Research, Sichuan University, Chengdu 610041, China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.[2]Sichuan Provincial Key Laboratory of Nuclear Physics and Medical Research, Sichuan University, Chengdu 610041, China.[3]College of Polymer Science and Engineering, State Key Laboratory of Advanced Polymer Materials, Sichuan University, Chengdu 610065, China.[4]Department of Endodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.[5]Institute of Chemistry and Biochemistry, Free University of Berlin, Berlin 14195, Germany.
推荐引用方式(GB/T 7714)：
Min Yu,Li Qian,Zhao Zhenyang,et al.Metallosalphen-Covalent Organic Framework-Based Semiconducting Artificial Enzymes with Radio-Activable Antitumor Immunity for Suppressing Tumor Metastasis and Recurrence[J].ACS Nano.2025,19(42):37373-37397.doi:10.1021/acsnano.5c13672.
APA：
Min Yu,Li Qian,Zhao Zhenyang,Wen Qinlong,Xu Wenjie...&Cheng Chong.(2025).Metallosalphen-Covalent Organic Framework-Based Semiconducting Artificial Enzymes with Radio-Activable Antitumor Immunity for Suppressing Tumor Metastasis and Recurrence.ACS Nano,19,(42)
MLA：
Min Yu,et al."Metallosalphen-Covalent Organic Framework-Based Semiconducting Artificial Enzymes with Radio-Activable Antitumor Immunity for Suppressing Tumor Metastasis and Recurrence".ACS Nano 19..42(2025):37373-37397
材料科学