Enhancing SDT Efficacy of Doxorubicin‐Loaded Sonosensitizer Micelles to Overcome Resistance of Cancer Therapy by Optimizing Acoustic Parameters
ABSTRACT Tumor drug resistance has been reported to be associated with drug efflux in tumor cells. Recently, a noninvasive and safe mechanism, sonodynamic therapy (SDT), has been proposed to be an oxidative stress strategy to potentially overcome drug efflux, but with efficacy limitation. Herein, we...
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2025-05-01
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| Online Access: | https://doi.org/10.1002/agt2.70005 |
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| author | Zhuoran Gong Deshang Hou Yunxue Xu Mengxuan Wang Shiyin Lin Yingjuan Zheng Zhifei Dai |
| author_facet | Zhuoran Gong Deshang Hou Yunxue Xu Mengxuan Wang Shiyin Lin Yingjuan Zheng Zhifei Dai |
| author_sort | Zhuoran Gong |
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| description | ABSTRACT Tumor drug resistance has been reported to be associated with drug efflux in tumor cells. Recently, a noninvasive and safe mechanism, sonodynamic therapy (SDT), has been proposed to be an oxidative stress strategy to potentially overcome drug efflux, but with efficacy limitation. Herein, we propose a systematic strategy for optimizing SDT, especially revealing the key role of acoustics parameters acting in SDT efficiency. A doxorubicin (DOX)‐loaded sonosensitive micelle (DPM) mediated “sono‐force” combination (chemotherapy and sonodynamic) therapy strategy, named DPCSTs, which was designed for amplifying SDT to augment oxidative stress to overcome drug efflux and induce robust long‐term inhibition of tumor development by optimized acoustic parameters. The sub‐10 nm size DPM enhanced tumor targeting and renal clearance. Meanwhile, another important component, doxorubicin, significantly suppressed residual tumors (78.6%) due to “sono‐force” augmented oxidative stress reversing drug efflux, finally leading to long‐term tumor development limitation in vivo. It is the first time to propose a systematic strategy for optimizing SDT regimens to overcome resistance, which can synergize with chemotherapy to exert long‐term tumor development inhibition. We believe that this work will advance SDT‐related research to a new level, and improve our understanding of overcoming resistance of targeted cancer therapy. |
| format | Article |
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| issn | 2692-4560 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
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| spelling | doaj-art-c3ada9df6d504a2f99a322bf2aca27ca2025-08-20T02:33:11ZengWileyAggregate2692-45602025-05-0165n/an/a10.1002/agt2.70005Enhancing SDT Efficacy of Doxorubicin‐Loaded Sonosensitizer Micelles to Overcome Resistance of Cancer Therapy by Optimizing Acoustic ParametersZhuoran Gong0Deshang Hou1Yunxue Xu2Mengxuan Wang3Shiyin Lin4Yingjuan Zheng5Zhifei Dai6Department of Biomedical Engineering College of Future Technology National Biomedical Imaging Center State Key Laboratory of Vascular Homeostasis and Remodeling Peking University Beijing ChinaDepartment of Biomedical Engineering College of Future Technology National Biomedical Imaging Center State Key Laboratory of Vascular Homeostasis and Remodeling Peking University Beijing ChinaDepartment of Biomedical Engineering College of Future Technology National Biomedical Imaging Center State Key Laboratory of Vascular Homeostasis and Remodeling Peking University Beijing ChinaDepartment of Biomedical Engineering College of Future Technology National Biomedical Imaging Center State Key Laboratory of Vascular Homeostasis and Remodeling Peking University Beijing ChinaDepartment of Biomedical Engineering College of Future Technology National Biomedical Imaging Center State Key Laboratory of Vascular Homeostasis and Remodeling Peking University Beijing ChinaDepartment of Hyperthermia and Photodynamic Treatment The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaDepartment of Biomedical Engineering College of Future Technology National Biomedical Imaging Center State Key Laboratory of Vascular Homeostasis and Remodeling Peking University Beijing ChinaABSTRACT Tumor drug resistance has been reported to be associated with drug efflux in tumor cells. Recently, a noninvasive and safe mechanism, sonodynamic therapy (SDT), has been proposed to be an oxidative stress strategy to potentially overcome drug efflux, but with efficacy limitation. Herein, we propose a systematic strategy for optimizing SDT, especially revealing the key role of acoustics parameters acting in SDT efficiency. A doxorubicin (DOX)‐loaded sonosensitive micelle (DPM) mediated “sono‐force” combination (chemotherapy and sonodynamic) therapy strategy, named DPCSTs, which was designed for amplifying SDT to augment oxidative stress to overcome drug efflux and induce robust long‐term inhibition of tumor development by optimized acoustic parameters. The sub‐10 nm size DPM enhanced tumor targeting and renal clearance. Meanwhile, another important component, doxorubicin, significantly suppressed residual tumors (78.6%) due to “sono‐force” augmented oxidative stress reversing drug efflux, finally leading to long‐term tumor development limitation in vivo. It is the first time to propose a systematic strategy for optimizing SDT regimens to overcome resistance, which can synergize with chemotherapy to exert long‐term tumor development inhibition. We believe that this work will advance SDT‐related research to a new level, and improve our understanding of overcoming resistance of targeted cancer therapy.https://doi.org/10.1002/agt2.70005acoustic parametersdrug resistancereactive oxygen speciessonodynamic therapy |
| spellingShingle | Zhuoran Gong Deshang Hou Yunxue Xu Mengxuan Wang Shiyin Lin Yingjuan Zheng Zhifei Dai Enhancing SDT Efficacy of Doxorubicin‐Loaded Sonosensitizer Micelles to Overcome Resistance of Cancer Therapy by Optimizing Acoustic Parameters Aggregate acoustic parameters drug resistance reactive oxygen species sonodynamic therapy |
| title | Enhancing SDT Efficacy of Doxorubicin‐Loaded Sonosensitizer Micelles to Overcome Resistance of Cancer Therapy by Optimizing Acoustic Parameters |
| title_full | Enhancing SDT Efficacy of Doxorubicin‐Loaded Sonosensitizer Micelles to Overcome Resistance of Cancer Therapy by Optimizing Acoustic Parameters |
| title_fullStr | Enhancing SDT Efficacy of Doxorubicin‐Loaded Sonosensitizer Micelles to Overcome Resistance of Cancer Therapy by Optimizing Acoustic Parameters |
| title_full_unstemmed | Enhancing SDT Efficacy of Doxorubicin‐Loaded Sonosensitizer Micelles to Overcome Resistance of Cancer Therapy by Optimizing Acoustic Parameters |
| title_short | Enhancing SDT Efficacy of Doxorubicin‐Loaded Sonosensitizer Micelles to Overcome Resistance of Cancer Therapy by Optimizing Acoustic Parameters |
| title_sort | enhancing sdt efficacy of doxorubicin loaded sonosensitizer micelles to overcome resistance of cancer therapy by optimizing acoustic parameters |
| topic | acoustic parameters drug resistance reactive oxygen species sonodynamic therapy |
| url | https://doi.org/10.1002/agt2.70005 |
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