Ruthenium Single-Atom Nanozyme Driven Sonosensitizer with Oxygen Vacancies Enhances Electron-Hole Separation Efficacy and Remodels Tumor Microenvironment for Sonodynamic-Amplified Ferroptosis

被引：0

作者：

Zhu, Yang ^{[1
,2
]}

Wang, Dengliang ^{[1
,2
]}

Du, Chengzhong ^{[1
,2
]}

Wu, Tiantian ^{[3
]}

Wei, Penghui ^{[1
,2
]}

Zheng, Hongjia ^{[1
,2
]}

Li, Guanting ^{[1
,2
]}

Zheng, ShunZhe ^{[1
,2
]}

Su, Lichao ^{[1
,2
]}

Yan, Lingjun ^{[1
,2
]}

Hu, Yongrui ^{[1
,2
]}

Wang, Huimin ^{[1
,2
]}

Lin, Lisen ^{[1
,2
]}

Ding, Chenyu ^{[1
,2
]}

Chen, Xiaoyuan ^{[4
,5
,6
,7
,8
,9
,10
]}

机构：

[1] Fujian Med Univ, Affiliated Hosp 1, Neurosurg Res Inst, Dept Neurosurg, Fuzhou 350209, Fujian, Peoples R China

[2] Fujian Med Univ, Affiliated Hosp 1, Natl Reg Med Ctr, Dept Neurosurg, Binhai Campus, Fuzhou 350212, Fujian, Peoples R China

[3] Hainan Med Univ, Sch Pharmaceut Sci, Sch Trop Med, NHC Key Lab Trop Dis Control, Haikou 571199, Peoples R China

[4] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Diagnost Radiol, Singapore 119074, Singapore

[5] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Surg, Singapore 119074, Singapore

[6] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Chem & Biomol Engn, Singapore 119074, Singapore

[7] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biomed Engn, Singapore 119074, Singapore

[8] Natl Univ Singapore, Coll Design & Engn, Singapore 119074, Singapore

[9] Natl Univ Singapore, Clin Imaging Res Ctr, Ctr Translat Med, Yong Loo Lin Sch Med, Singapore 117599, Singapore

[10] Natl Univ Singapore, Yong Loo Lin Sch Med, Nanomed Translat Res Program, Singapore 117597, Singapore

来源：

ADVANCED SCIENCE | 2025年

基金：

英国医学研究理事会; 中国国家自然科学基金;

关键词：

ferroptosis; oxygen vacancy; single-atom nanozyme; sonodynamic therapy; tumor microenvironment; THERAPY;

D O I：

10.1002/advs.202416997

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Sonodynamic therapy (SDT) has emerged as a promising noninvasive approach for tumor therapy. However, the effectiveness of traditional inorganic semiconductor sonosensitizers is hindered by rapid electron (e-) and hole (h+) recombination under ultrasonic (US) stimulation, as well as the hypoxic and reductive conditions of tumor microenvironment (TME), which limit the generation of reactive oxygen species (ROS). Herein, a ruthenium (Ru) single-atom nanozyme-driven superimposition-enhanced titanium dioxide-based sonosensitizer (Ru/TiO2-x SAE) is presented that features sufficient oxygen vacancies and high e-/h+ separation efficiency. Through synchrotron radiation-based X-ray absorption spectroscopy and extended X-ray absorption fine structure analysis it is confirmed that oxygen vacancies in TiO2-x nanoparticles promote the immobilization of single-atomic Ru, forming Ru-O-4 active sites. Density functional theory calculations demonstrate that oxygen vacancies alter the electronic structure of nanosensitizer, enhanced e-/h+ separation, increasing oxygen adsorption, and accelerating reaction kinetics under US stimulation, ultimately improving ROS production. Moreover, Ru/TiO2-x SAE boosts sonodynamic efficacy by mitigating the hypoxic and reductive TME. This is attributed to its catalase- and glutathione peroxidase 4-like activities, which facilitate the generation of ROS and trigger lipid peroxidation-mediated ferroptosis. These findings highlight the innovative role of single-atom Ru in optimizing sonosensitizers for SDT-induced ferroptosis, demonstrating its potential for advancing cancer therapy.

引用

页数：13