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Theranostics 2022; 12(11):5155-5171. doi:10.7150/thno.73039 This issue Cite

Research Paper

Tumor microenvironment-activated single-atom platinum nanozyme with H₂O₂ self-supplement and O₂-evolving for tumor-specific cascade catalysis chemodynamic and chemoradiotherapy

Qiqi Xu^1,2*, Yuetong Zhang^1,2*, Zulu Yang^1,2, Guohui Jiang⁶, Mingzhu Lv^1,2, Huan Wang^1,2, Chenghui Liu^1,2, Jiani Xie⁴, Chengyan Wang³, Kun Guo⁵, Zhanjun Gu³, Yuan Yong^1,2✉

1. Key Laboratory of Pollution Control Chemistry and Environmental Functional Materials for Qinghai-Tibet Plateau of the National Ethnic Affairs Commission, School of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, China.
2. Key Laboratory of General Chemistry of the National Ethnic Affairs Commission, School of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, China.
3. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing100040, China.
4. College of Pharmacy and Biological Engineering, Chengdu University, Chengdu, 610106, China.
5. College of Pharmacy, Southwest Minzu University, Chengdu 610041, China.
6. Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China.
*These authors contributed equally.

✉ Corresponding author: Yuan Yong, E-mail: yongy1816com

Abstract

Nanozyme-based tumor collaborative catalytic therapy has attracted a great deal of attention in recent years. However, their cooperative outcome remains a great challenge due to the unique characteristics of tumor microenvironment (TME), such as insufficient endogenous hydrogen peroxide (H₂O₂) level, hypoxia, and overexpressed intracellular glutathione (GSH).

Methods: Herein, a TME-activated atomic-level engineered PtN₄C single-atom nanozyme (PtN₄C-SAzyme) is fabricated to induce the “butterfly effect” of reactive oxygen species (ROS) through facilitating intracellular H₂O₂ cycle accumulation and GSH deprivation as well as X-ray deposition for ROS-involving CDT and O₂-dependent chemoradiotherapy.

Results: In the paradigm, the SAzyme could boost substantial ∙OH generation by their admirable peroxidase-like activity as well as X-ray deposition capacity. Simultaneously, O₂ self-sufficiency, GSH elimination and elevated Pt²⁺ release can be achieved through the self-cyclic valence alteration of Pt (IV) and Pt (II) for alleviating tumor hypoxia, overwhelming the anti-oxidation defense effect and overcoming drug-resistance. More importantly, the PtN₄C-SAzyme could also convert O₂^·- into H₂O₂ by their superior superoxide dismutase-like activity and achieve the sustainable replenishment of endogenous H₂O₂, and H₂O₂ can further react with the PtN₄C-SAzyme for realizing the cyclic accumulation of ∙OH and O₂ at tumor site, thereby generating a “key” to unlock the multi enzymes-like properties of SAzymes for tumor-specific self-reinforcing CDT and chemoradiotherapy.

Conclusions: This work not only provides a promising TME-activated SAzyme-based paradigm with H₂O₂ self-supplement and O₂-evolving capacity for intensive CDT and chemoradiotherapy but also opens new horizons for the construction and tumor catalytic therapy of other SAzymes.

Keywords: Single-atom nanozyme, tumor microenvironment-activated, enzyme-like activity, tumor catalytic therapy, chemodynamic and chemoradiotherapy

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