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<p>Efficient synthesis of chemotherapeutic drugs within the tumor microenvironment (TME) holds great potential for enhancing sonodynamic-mediated synergistic oncotherapy. Herein, an engineered nanoreactor composed of Cu<sup>2+</sup>, indocyanine green (ICG), and 1,5-dihydroxynaphthalene (DHN) (termed DCI) with self-amplifying reactive oxygen species (ROS) and cascade chemo-drug synthesis in tumor cells was constructed by coordination-driven co-assembly of sonosensitizer ICG, transition metal copper (Cu<sup>2+</sup>), and nontoxic DHN. Upon intravenous administration, DCI selectively accumulated in tumor tissues and performed excellent photoacoustic (PA) and near-infrared fluorescence (NIRF) imaging capabilities compared to free ICG. Once DCI was internalized into tumor cells, it rapidly disassembled and generated a chemo-drug under the stimuli of acidic lysosome and sonodynamic radiation. The released Cu<sup>2+</sup> efficiently decomposed endogenous hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) into hydroxyl radical (·OH) and O<sub>2</sub> and glutathione (GSH). The generated O<sub>2</sub> efficiency alleviated tumor hypoxia and enhanced sonodynamic therapy (SDT) efficiency. Notably, a large amount of the singlet oxygen (<sup>1</sup>O<sub>2</sub>) generated by SDT could efficiently oxidize the released nontoxic DHN into hydroxynaphthoquinone (HPN) with higher toxicity. Overall, this work provides a simple, flexible, and effective strategy for oncotherapy.</p> Graphical Abstract <p></p>

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Copper-coordinated engineered nanoreactors with self-amplifying O2 and cascade chem-drug synthesis for enhanced sonodynamic-mediated oncotherapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月9日

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  • Zhongxiong Fan,
  • Lijun Ding,
  • Fukai Zhu,
  • Nan Yang,
  • Yanrong Shi,
  • Qian Sun,
  • Jun Hai,
  • Jinyao Li,
  • Guanghao Su,
  • Zhenqing Hou

摘要

Efficient synthesis of chemotherapeutic drugs within the tumor microenvironment (TME) holds great potential for enhancing sonodynamic-mediated synergistic oncotherapy. Herein, an engineered nanoreactor composed of Cu2+, indocyanine green (ICG), and 1,5-dihydroxynaphthalene (DHN) (termed DCI) with self-amplifying reactive oxygen species (ROS) and cascade chemo-drug synthesis in tumor cells was constructed by coordination-driven co-assembly of sonosensitizer ICG, transition metal copper (Cu2+), and nontoxic DHN. Upon intravenous administration, DCI selectively accumulated in tumor tissues and performed excellent photoacoustic (PA) and near-infrared fluorescence (NIRF) imaging capabilities compared to free ICG. Once DCI was internalized into tumor cells, it rapidly disassembled and generated a chemo-drug under the stimuli of acidic lysosome and sonodynamic radiation. The released Cu2+ efficiently decomposed endogenous hydrogen peroxide (H2O2) into hydroxyl radical (·OH) and O2 and glutathione (GSH). The generated O2 efficiency alleviated tumor hypoxia and enhanced sonodynamic therapy (SDT) efficiency. Notably, a large amount of the singlet oxygen (1O2) generated by SDT could efficiently oxidize the released nontoxic DHN into hydroxynaphthoquinone (HPN) with higher toxicity. Overall, this work provides a simple, flexible, and effective strategy for oncotherapy.

Graphical Abstract