Construction of TiO2@Ag2O p-n junctions for synergistic sonodynamic/sonothermal tumor therapy with enhanced efficacy

Zhizi Ma; Zhuang Yang; Jie Ma; Sainan Liu; Qi Meng; Wenying Zhang; Ziyong Cheng; Zhangfeng Wang; Abdulaziz A Al Kheraif; Ping'an Ma; Jun Lin

doi:10.1016/j.actbio.2025.06.049

Construction of TiO₂@Ag₂O p-n junctions for synergistic sonodynamic/sonothermal tumor therapy with enhanced efficacy

Acta Biomater. 2025 Jun 26:S1742-7061(25)00468-4. doi: 10.1016/j.actbio.2025.06.049. Online ahead of print.

Authors

Zhizi Ma¹, Zhuang Yang¹, Jie Ma¹, Sainan Liu¹, Qi Meng¹, Wenying Zhang¹, Ziyong Cheng², Zhangfeng Wang³, Abdulaziz A Al Kheraif⁴, Ping'an Ma⁵, Jun Lin⁶

Affiliations

¹ School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China; State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
² Key Laboratory of Superlight Materials & Surface Technology of Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin, 150001, China. Electronic address: zycheng@ciac.ac.cn.
³ Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun 130022, P. R. China.
⁴ Dental Health Department, College of Applied Medical Sciences, King Saud University, Riyadh 12372, Saudi Arabia.
⁵ School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China; State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China. Electronic address: mapa675@ciac.ac.cn.
⁶ School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China; State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China. Electronic address: jlin@ciac.ac.cn.

PMID: 40581031
DOI: 10.1016/j.actbio.2025.06.049

Abstract

With the deepening of research of sonodynamic therapy (SDT), it is shown that the efficacy of single component and single functional sonosensitizers is not satisfactory. Therefore, this study utilized multihole TiO₂@Ag₂O (TA) as sonosensitizer to achieve synergetic SDT and sonothermal therapy (STT) under US irradiation. As a p-n nanoformulation, the construction of TA is conducive to generate a built-in electric field and lead to energy band bending, which are efficient in separating electrons and holes. Besides, it can promote carrier relaxation between the different energy bands to produce abundant phonons, inducing lattice thermal vibration and realizing the conversion of mechanical energy to thermal energy. Moreover, the feasibility of enhancing cavitation effect for improving sonothermal capability is demonstrated for the first time. When TA enters tumor cells under US irradiation, plentiful ⚫OH and ¹O₂ are generated to attack mitochondria, causing dysfunction, disrupting energy supply and damaging DNA, thereby inducing apoptosis. Meanwhile, TA can also cause rapid local heating of surrounding environment to kill tumor cells by lattice thermal vibration and cavitation bubbles bursting on its surface. Obviously, this work effectively achieves both heterojunction enhanced SDT, and carrier relaxation and cavitation effect promoted STT combined anti-tumor therapy through designing multihole p-n TA. STATEMENT OF SIGNIFICANCE: None.

Keywords: anti-tumor; cavitation effect; p-n junction; sonodynamic therapy; sonothermal therapy.