Copper-Based Single-Atom Nanozyme System Mimicking Platelet Cells for Enhancing the Outcome of Radioimmunotherapy

Abstract

Background

Radiotherapy is an indispensable part of the multidisciplinary treatment of breast cancer (BC). Due to the potential for serious side effects from ionizing radiation in the treatment of breast cancer, which can adversely affect the patient’s quality of life, the radiation dose is often limited. This limitation can result in an incomplete eradication of tumors.

Methods

In this study, biomimetic copper single-atom catalysts (platelet cell membrane camouflaging, PC) were synthesized with the aim of improving the therapeutic outcomes of radiotherapy for BC. Following guidance to the tumor site facilitated by the platelet cell membrane coating, PC releases a copper single-atom nanozyme (SAzyme). This SAzyme enhances therapeutic effects by generating reactive oxygen species from H₂O₂ and concurrently inhibiting the self-repair mechanisms of cancer cells through the consumption of intracellular glutathione (GSH) within the tumor microenvironment. PC-augmented radiotherapy induces immunogenic cell death, which triggers an immune response to eradicate tumors.

Results

With the excellent biocompatibility, PC exhibited precise tumor-targeting capabilities. Furthermore, when employed in conjunction with radiotherapy, PC showed impressive tumor elimination results through immunological activation. Remarkably, the tumor suppression rate achieved with PC-enhanced radiotherapy reached an impressive 93.6%.

Conclusion

Therefore, PC presents an innovative approach for designing radiosensitizers with tumor-specific targeting capabilities, aiming to enhance the therapeutic impact of radiotherapy on BC.

Keywords:

• platelet cell membrane
• single-atom nanozyme
• radiotherapy
• radioimmunotherapy
• breast cancer

Acknowledgments

Cheng Chen, Nandi Chen, Yan Qi and Chaoyan Wu contributed equally to this work. The authors would like to thank all the reviewers who participated in the review and MJEditor (www.mjeditor.com) for its linguistic assistance during the preparation of this manuscript.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was financially supported by National Natural Science Foundation of China (Grant No. 82073349), the Technology & Innovation Commission of Shenzhen Municipality (Shenzhen, China, Grant No. JCYJ20190807145011340), and Shenzhen High-tech Development Special Plan-Pingshan District Innovation Platform Project (29853M-KCJ-2023-002-04).