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<p>Stimuli-responsive nanocarriers capable of preferentially delivering both sonosensitizers and chemoagents to cancer cells are effective for cancer treatment. In this study, glutathione (GSH)-responsive diselenide linker-bearing fatty amine derivative (DSe) was formulated with non-ionic polysorbate Tween 80 (T80) to fabricate micelles for the biocompatible and tumor-selective delivery of mitochondria-specific sonosensitizers [triphenylphosphonium-conjugated chlorin e6 (TPP-Ce6)] and chemoagents (doxorubicin, DOX). T80-DSe-based micelles effectively co-encapsulated both DOX and TPP-Ce6. Bioreducible T80-DSe-based micelles co-encapsulating DOX and TPP-Ce6 (T80-DSe-DTC) exhibited GSH-responsive drug release, promoting the cytoplasmic release of its cargo in the reducing environment of tumor cells. Upon ultrasound (US) irradiation, the TPP-Ce6 released from the micelles effectively disrupted cellular mitochondria, leading to accelerated apoptotic cell death. Bioreducible micelles significantly increased intracellular reactive oxygen species (ROS) under US irradiation. Therefore, T80-DSe-DTC combined with US irradiation, leveraging both mitochondria-targeted sonodynamic therapy (SDT) and chemotherapy, exhibited significant anticancer effects against human breast cancer cells. This study demonstrates the potential of bioreducible T80 micelles co-encapsulating sonosensitizers and chemoagents for achieving efficient chemo-SDT.</p> Graphical abstract <p></p>

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Bioreducible polysorbate-based micelles encapsulating mitochondria-targeting sonosensitizers for efficient chemo-sonodynamic cancer therapy

  • 期刊论文

  • 发表日期：

    2025年6月27日

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  • Hyeon Ju Kang,
  • Jun Min,
  • Vasanthan Ravichandran,
  • Quan Truong Hoang,
  • Le Thi Hong Tram,
  • Byoung Choul Kim,
  • Min Suk Shim

摘要

Stimuli-responsive nanocarriers capable of preferentially delivering both sonosensitizers and chemoagents to cancer cells are effective for cancer treatment. In this study, glutathione (GSH)-responsive diselenide linker-bearing fatty amine derivative (DSe) was formulated with non-ionic polysorbate Tween 80 (T80) to fabricate micelles for the biocompatible and tumor-selective delivery of mitochondria-specific sonosensitizers [triphenylphosphonium-conjugated chlorin e6 (TPP-Ce6)] and chemoagents (doxorubicin, DOX). T80-DSe-based micelles effectively co-encapsulated both DOX and TPP-Ce6. Bioreducible T80-DSe-based micelles co-encapsulating DOX and TPP-Ce6 (T80-DSe-DTC) exhibited GSH-responsive drug release, promoting the cytoplasmic release of its cargo in the reducing environment of tumor cells. Upon ultrasound (US) irradiation, the TPP-Ce6 released from the micelles effectively disrupted cellular mitochondria, leading to accelerated apoptotic cell death. Bioreducible micelles significantly increased intracellular reactive oxygen species (ROS) under US irradiation. Therefore, T80-DSe-DTC combined with US irradiation, leveraging both mitochondria-targeted sonodynamic therapy (SDT) and chemotherapy, exhibited significant anticancer effects against human breast cancer cells. This study demonstrates the potential of bioreducible T80 micelles co-encapsulating sonosensitizers and chemoagents for achieving efficient chemo-SDT.

Graphical abstract