Single Atom‐Doped Nanosonosensitizers for Mutually Optimized Sono/Chemo‐Nanodynamic Therapy of Triple Negative Breast Cancer
Open accessAbstract
Sonodynamic therapy (SDT) represents a promising therapeutic modality for treating breast cancer, which relies on the generation of abundant reactive oxygen species (ROS) to induce oxidative stress damage. However, mutant breast cancers, especially triple‐negative breast cancer (TNBC), have evolved to acquire specific antioxidant defense functions, significantly limiting the killing efficiency of SDT. Herein, the authors have engineered a distinct single copper atom‐doped titanium dioxide (Cu/TiO 2) nanosonosensitizer with highly catalytic and sonosensitive activities for synergistic chemodynamic and sonodynamic treatment of TNBC. The single‐atom Cu is anchored on the most stable Ti vacancies of hollow TiO 2 sonosensitizers, which not only substantially improved the catalytic activity of Cu‐mediated Fenton‐like reaction, but also considerably augmented the sonodynamic efficiency of TiO 2 by facilitating the separation of electrons (e−) and holes (h+). Both the in vitro and in vivo studies demonstrate that the engineered single atom‐doped nanosonosensitizers effectively achieved the significantly inhibitory effect of TNBC, providing a therapeutic paradigm for non‐invasive and safe tumor elimination through the mutual process of sono/chemo‐nanodynamic therapy based on multifunctional single‐atom nanosonosensitizers.
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ROS generated by Cu/TiO2 synergistic therapy cause extensive DNA damage, activating the p53 signalling pathway to induce apoptosis, and ROS-dependent inhibition of oxidative phosphorylation induces an energy crisis and apoptosis of cancer cells.
“It was found that ROS generated by the synergistic therapy could cause extensive DNA damage, which could activate the p53 signalling pathway to induce apoptosis. In addition, ROS-dependent inhibition of oxidative phosphorylation occurs, thereby inducing an energy crises and apoptosis of cancer cells.”
From Nanosensitizer-assisted sonodynamic therapy for breast cancer (2025) · cites this paper as [125]
The inhibition rate of Cu/TiO2 and ultrasound treatment of breast tumors in 4T1-bearing mice was 70.35%, compared to 30.91% in the TiO2 and ultrasound group.
“In addition, the inhibition rate of the Cu/TiO2 and US treatment of breast tumors in 4T1-bearing mice was the highest at 70.35%, particularly compared to the TiO2 and US group (30.91%).”
From Nanosensitizer-assisted sonodynamic therapy for breast cancer (2025) · cites this paper as [125]
The percentage of apoptotic 4T1 cells in the Cu/TiO2 and ultrasound group was 99.4%, which was much higher than that in the TiO2 and ultrasound group (86%).
“The percentage of apoptotic 4T1 cells in the Cu/TiO2 and US (1.0 Wcm−2, 1 MHz, 50% duty cycle, 5 min) group was 99.4%, which was much higher than that in the TiO2 and US group (86%).”
From Nanosensitizer-assisted sonodynamic therapy for breast cancer (2025) · cites this paper as [125]
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Nanosensitizer-assisted sonodynamic therapy for breast cancer
Yu, J., Hu, J.-R., Tian, Y., Lei, Y.-M., Hu, H.-M., Lei, B.-S., Zhang, G., Sun, Y., & Ye, H.-R. (2025) · Journal of Nanobiotechnology · doi:10.1186/s12951-025-03311-3 · Cited by 43 · see citing works
- Authors
- Chen, Q., Zhang, M., Huang, H., Dong, C., Dai, X., Feng, G., Lin, L., Sun, D., Yang, D., Xie, L., Chen, Y., Guo, J., & Jing, X.
- Affiliations
- Hainan General Hospital (CN)
- Shanghai University (CN)
- Shanghai Medical College of Fudan University (CN)
- Shanghai University of Traditional Chinese Medicine (CN)
- Corresponding author
- Chen, Yu
- Guo, Jia
- Jing, Xiangxiang
- ORCID
- Venue
- Advanced Science
- Publisher
- Wiley
- Published
- 2023-01-16
- Volume
- 10
- Issue
- 6
- Pages
- e2206244-e2206244
- ISSN
- 2198-3844 (ISSN-L)
- PMC
- PMC9951334
- OpenAlex
- W4316927664
- Cited by
- 83
- References
- 3
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 36 · 2023: 15
- FWCI
- 6.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Advanced Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (82160337, 81760317, 81871365)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Physical Sciences › Materials Science › Materials Chemistry › Advanced Nanomaterials in Catalysis
- Keywords
- sonodynamic therapy, triple-negative breast cancer, single-atom doping, copper-doped titanium dioxide, chemodynamic therapy, Fenton-like reaction, Ti vacancies, reactive oxygen species, antioxidant defense, electron-hole separation, synergistic cancer therapy
- MeSH terms
- Humans, Titanium, Ultrasonic Therapy, Reactive Oxygen Species, Triple Negative Breast Neoplasms
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