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Single Atom-Doped Nanosonosensitizers for Mutually Optimized Sono/Chemo-Nanodynamic Therapy of Triple Negative Breast
Qiqing Chen1, Min Zhang1, Hui Huang2
1Department of Ultrasonography, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, P. R. China.
Abstract:
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/TiO2 ) 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 TiO2 sonosensitizers, which not only substantially improved the catalytic activity of Cu-mediated Fenton-like reaction, but also considerably augmented the sonodynamic efficiency of TiO2 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.
Insights
Engineered single copper atom-doped titanium dioxide (Cu/TiO2) nanosonosensitizers enhance sonodynamic therapy for triple-negative breast cancer (TNBC). This novel approach boosts ROS generation and tumor inhibition, offering a safe, non-invasive treatment strategy.
Area of Science:
- Nanotechnology
- Materials Science
- Biomedical Engineering
Background:
- Sonodynamic therapy (SDT) shows promise for breast cancer treatment by generating reactive oxygen species (ROS).
- Triple-negative breast cancer (TNBC) exhibits antioxidant defenses that limit SDT efficacy.
- Novel nanosonosensitizers are needed to overcome resistance and improve SDT outcomes.
Purpose of the Study:
- To engineer a single copper atom-doped titanium dioxide (Cu/TiO2) nanosonosensitizer.
- To enhance synergistic chemodynamic and sonodynamic therapy for TNBC.
- To investigate the therapeutic potential of this novel nanosonosensitizer in vitro and in vivo.
Main Methods:
- Synthesis of hollow TiO2 sonosensitizers with single copper atoms anchored on Ti vacancies.
- Evaluation of catalytic activity for Cu-mediated Fenton-like reactions.
- Assessment of sonodynamic efficiency and electron-hole separation.
- In vitro and in vivo studies on TNBC inhibition.
Main Results:
- The engineered Cu/TiO2 nanosonosensitizers exhibited enhanced catalytic and sonosensitive activities.
- Improved Fenton-like reaction and facilitated electron-hole separation in TiO2.
- Significant inhibition of TNBC growth in both in vitro and in vivo models.
- Demonstrated synergistic sono/chemo-nanodynamic therapeutic effects.
Conclusions:
- Single-atom Cu doping significantly enhances the performance of TiO2 nanosonosensitizers for TNBC treatment.
- The engineered nanosonosensitizers provide a multifunctional platform for synergistic sono/chemo-nanodynamic therapy.
- This approach offers a promising non-invasive and safe therapeutic strategy for TNBC elimination.
