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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Main Authors: Zhuoran Gong, Deshang Hou, Yunxue Xu, Mengxuan Wang, Shiyin Lin, Yingjuan Zheng, Zhifei Dai
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Aggregate
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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
collection DOAJ
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.
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issn 2692-4560
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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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