Camouflaged membrane-bridged radionuclide/Mn single-atom enzymes target lipid metabolism disruption to evoke antitumor immunity

Meng-Die Yang; Chun-Yan Zhu; Gang Yang; Xiao-Yi Zhang; Yi Zhu; Miao Chen; Jia-Jia Zhang; Ling Bai; Shan-Shan Qin; Chao Ma; Fei Yu; Kun Zhang

doi:10.1186/s40779-025-00647-7

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Camouflaged membrane-bridged radionuclide/Mn single-atom enzymes target lipid metabolism disruption to evoke antitumor immunity

RESEARCH | Updated：2026-05-08

- Camouflaged membrane-bridged radionuclide/Mn single-atom enzymes target lipid metabolism disruption to evoke antitumor immunity
- Camouflaged membrane-bridged radionuclide/Mn single-atom enzymes target lipid metabolism disruption to evoke antitumor immunity
- Military Medical Research 2026年13卷第3期页码：365-384
- Affiliations：
  
  1.Department of Nuclear Medicine, Shanghai Tenth People’s Hospital and Institute of Nuclear Medicine, School of Medicine, Tongji University, Shanghai 200072, China
  2.Central Laboratory, Department of Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
  3.Department of Nuclear Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China
  4.Department of Pathology, School of Medicine, Duke University, Durham, NC 27710, USA
- Author bio：
  
  * Fei Yu yufei_021@163.com; 0910110013yufei@tongji.edu.cn
  Kun Zhang zhang1986kun@tongji.edu.cn; zhang1986kun@126.com
- Funds：
  
  the National Natural Science Foundation of China(82272030;82022033;82071956);the Construction Project of Shanghai Key Laboratory of Molecular Imaging(18DZ2260400);the Sichuan Provincial Science and Technology Program(2024NSFJQ0048;2024NSFTD0024)
- DOI：10.1186/s40779-025-00647-7
  中图分类号：
- 收稿：2025-02-28，
  
  录用：2025-09-04，
  
  网络首发：2025-09-19，
  
  纸质出版：2026-03
- Accepted：
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Meng-Die Yang, Chun-Yan Zhu, Gang Yang, 等. Camouflaged membrane-bridged radionuclide/Mn single-atom enzymes target lipid metabolism disruption to evoke antitumor immunity[J]. Military Medical Research, 2026,13(3):365-384.

Meng-Die Yang, Chun-Yan Zhu, Gang Yang, et al. Camouflaged membrane-bridged radionuclide/Mn single-atom enzymes target lipid metabolism disruption to evoke antitumor immunity[J]. Military Medical Research, 2026, 13(3): 365-384.
Meng-Die Yang, Chun-Yan Zhu, Gang Yang, 等. Camouflaged membrane-bridged radionuclide/Mn single-atom enzymes target lipid metabolism disruption to evoke antitumor immunity[J]. Military Medical Research, 2026,13(3):365-384. DOI： 10.1186/s40779-025-00647-7.

Meng-Die Yang, Chun-Yan Zhu, Gang Yang, et al. Camouflaged membrane-bridged radionuclide/Mn single-atom enzymes target lipid metabolism disruption to evoke antitumor immunity[J]. Military Medical Research, 2026, 13(3): 365-384. DOI： 10.1186/s40779-025-00647-7.

摘要

Abstract

Background

Lipid metabolic reprogramming has been increasingly recognized as a key factor contributing to tumor immune evasion

therapeutic resistance

and plasticity

which collectively compromise the efficacy of targeted radionuclide therapy (TRT). Overcoming the immunosuppressive and hypoxic tumor microenvironment (TME) while interfering with tumor lipid metabolism may offer a promising strategy to potentiate TRT outcomes.

Methods

In this report

a radiopharmaceutical with multienzymatic catalysis activities is developed

wherein tumor cell membrane-coated manganese single-atom nanozymes (Mn/SAE@M) as supports deliver iodine-131 (

131

I) to the tumor. The Mn/SAE nanozyme core was synthesized in situ within hollow mesoporous zeolitic imidazolate frame-8 (ZIF-8) nanoparticles

then coated with homologous tumor cell membranes for targeted delivery and subsequently labeled with

131

I using the Chloramine-T method. A series of in vitro and in vivo experiments was performed in non-small cell lung cancer (NSCLC) models to evaluate therapeutic efficacy and immune activation.

Results

131

I-Mn/SAE@M exhibited efficient tumor targeting and internalization mediated by membrane camouflage. Within the TME

the radiopharmaceuticals initiated abundant oxygen (O

) release through catalase (CAT)-like catalysis

thereby mitigating a hypoxic microenvironment. In particular

it produced and enriched more reactive oxygen species(ROS) through oxidase (OXD)-

peroxidase (POD)-

and glutathione oxidase (GSHOx)-like catalytic processes. Importantly

131

I-Mn/SAE@M activated the cGAS-STING pathway

interfered with the lipid metabolic homeostasis of tumor cells

and induced ferroptosis

which is unraveled to take responsibil

ity for the potentiated antitumor immunity. In bilateral NSCLC tumor-bearing mice

the treatment suppressed both the first and the second tumors

indicating the generation of systemic antitumor immune responses and immunological memory.

Conclusions

Such SAE-based radiopharmaceuticals provide a candidate platform to elevate TRT efficiency

and the proof-of-concept rationale of disrupting lipid metabolic homeostasis through multienzyme-mimicking cascade reactions also provides a general avenue to improve TRT and synergistically magnify antitumor immunity.

关键词

Keywords

references

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