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<p>The encapsulation of sonosensitizers in exosomes has emerged as a potent strategy to enhance the therapeutic outcomes of sonodynamic therapy (SDT). Recently, milk-derived exosome (MExo) has gained significant attention as a scalable and cost-effective alternative to conventional exosomes derived from cell cultures. In this study, glutathione (GSH)-responsive MExos were developed to facilitate the efficient intracellular delivery of sonosensitizers (chlorin e6, Ce6) into human breast cancer cells by leveraging their elevated GSH concentrations. GSH-cleavable diselenide bond-bearing fatty amine derivative (DSe) was incorporated into MExos to achieve GSH-responsive drug release in cancer cells. DSe-incorporated MExo (DMExo) facilitated the release of Ce6 in the reductive cytoplasm. This led to enhanced generation of reactive oxygen species after ultrasound (US) treatment. As a result, Ce6-loaded DMExo triggered significant cell death in MCF-7 human breast cancer cells upon US exposure. These results demonstrate that bioreducible MExo is a safe and effective carrier for efficient SDT against cancer cells.</p> Graphical Abstract <p></p> <p>GSH-sensitive Ce6-DMExo facilitates the cytoplasmic release of Ce6 in response to high intracellular concentrations of GSH. The enhanced release of the sonosensitizer generates reactive oxygen species (ROS) under US exposure, which induces apoptotic cell death in cancer cells.</p>

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Glutathione-responsive milk-derived exosomes for safe and efficient sonodynamic cancer therapy

  • 期刊论文

  • 发表日期：

    2026年4月7日

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  • Dae Gyun Lee,
  • Jun Hyeok Choi,
  • Seong Jin Gwak,
  • Thuy Giang Nguyen Cao,
  • Le Thi Hong Tram,
  • Won Jong Rhee,
  • Byoung Choul Kim,
  • Min Suk Shim

摘要

The encapsulation of sonosensitizers in exosomes has emerged as a potent strategy to enhance the therapeutic outcomes of sonodynamic therapy (SDT). Recently, milk-derived exosome (MExo) has gained significant attention as a scalable and cost-effective alternative to conventional exosomes derived from cell cultures. In this study, glutathione (GSH)-responsive MExos were developed to facilitate the efficient intracellular delivery of sonosensitizers (chlorin e6, Ce6) into human breast cancer cells by leveraging their elevated GSH concentrations. GSH-cleavable diselenide bond-bearing fatty amine derivative (DSe) was incorporated into MExos to achieve GSH-responsive drug release in cancer cells. DSe-incorporated MExo (DMExo) facilitated the release of Ce6 in the reductive cytoplasm. This led to enhanced generation of reactive oxygen species after ultrasound (US) treatment. As a result, Ce6-loaded DMExo triggered significant cell death in MCF-7 human breast cancer cells upon US exposure. These results demonstrate that bioreducible MExo is a safe and effective carrier for efficient SDT against cancer cells.

Graphical Abstract

GSH-sensitive Ce6-DMExo facilitates the cytoplasmic release of Ce6 in response to high intracellular concentrations of GSH. The enhanced release of the sonosensitizer generates reactive oxygen species (ROS) under US exposure, which induces apoptotic cell death in cancer cells.