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Vol. 19 (2027)

IrMn-Cluster-Based Artificial Metalloenzymes with Radiosensitized Systemic Antitumor Responses to Prevent Malignant Tumor Metastasis and Recurrence

https://doi.org/10.1007/s40820-026-02309-2
Ruidan Li
Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China
Qinlong Wen
Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China
Zhenyu Xing
State Key Laboratory of Advanced Polymer Materials, College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, People’s Republic of China
Ting Wang
State Key Laboratory of Advanced Polymer Materials, College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, People’s Republic of China
Jing Yang
Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China
Yunfeng Tao
Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China
Shengdong Mu
College of Biological Engineering, Sichuan University of Science and Engineering, 188 University Town, Yibin, People’s Republic of China
Shuang Li
State Key Laboratory of Advanced Polymer Materials, College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, People’s Republic of China
Zhigong Wei
Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China
Chong Cheng
State Key Laboratory of Advanced Polymer Materials, College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, People’s Republic of China
Xingchen Peng
Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China

Corresponding Author: Xingchen Peng

pxx2014@scu.edu.cn

Nano-Micro Letters, Vol. 19 (2027), Article Number: 4

Abstract

Developing radiosensitizing agents to amplify tumor-eradicating effects on primary, regional recurrence, and distant metastases plays a transformative role in modern cancer care. Here, we report the de novo design of biocatalytic artificial metalloenzymes with an IrMn-cluster-based redox center (IMM) to achieve radiosensitized systemic antitumor responses for preventing malignant tumor metastasis and recurrence. Notably, our findings indicate that Mn-organic ligands substantially enrich the electron density of Ir clusters, thereby optimizing their interaction with oxygen species and markedly enhancing the production of both reactive oxygen species and molecular oxygen. When combined with radiotherapy, the IMM effectively amplifies DNA damage and induces pronounced apoptosis by alleviating intratumoral hypoxia. This shift reprograms the tumor microenvironment, enhancing radiosensitivity and facilitating the infiltration and activation of intratumoral CD8⁺ T cells and dendritic cells. Moreover, when integrated with anti-PD-1 therapy, this coordinated therapeutic regimen elicits potent systemic immune responses and durable antitumor memory, effectively suppressing tumor recurrence and metastasis while markedly improving therapeutic efficacy and long-term survival. We anticipate that this conceptual design could offer a promising and translationally relevant nanomedicine platform for radiotherapies.


Highlights:
1 The bioinspired design of IrMn-based redox centers (IMM) with rapid electron transfer can promote the formation of electron-rich IMM, thereby guaranteeing superior radio-enhanced reactive oxygen species biocatalysis and O2 generation.
2 The tumor-adaptive and biocompatible IMM can induce mitochondrial dysfunction and hinder DNA repair, resulting in robust immunogenic cell death.
3 An IMM-based biocatalyst can activate systemic antitumor responses and reverse a suppressive tumor microenvironment, thereby boosting tumoricidal effects and preventing metastasis and recurrence by synergizing with checkpoint blockade therapy.

Keywords

Bioinspired nanomedicines Artificial metalloenzymes Reactive oxygen species Antitumor therapy Malignant tumor
Li, Ruidan, Qinlong Wen, Zhenyu Xing, Ting Wang, Jing Yang, Yunfeng Tao, Shengdong Mu, Shuang Li, Zhigong Wei, Chong Cheng, and Xingchen Peng. 2026. “IrMn-Cluster-Based Artificial Metalloenzymes With Radiosensitized Systemic Antitumor Responses to Prevent Malignant Tumor Metastasis and Recurrence”. Nano-Micro Letters 19 (July):4. https://doi.org/10.1007/s40820-026-02309-2.
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