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<p>Reactive oxygen species (ROS)-mediated therapeutic modalities, including photodynamic therapy (PDT) and copper ion-mediated chemodynamic therapy (CDT), have been recognized as highly promising non-invasive strategies for cancer treatment. However, their therapeutic efficacy is frequently restricted by poor subcellular targeting capability. To address this challenge, a mitochondria-targeted nanoplatform (Cu@GO-PEG-Ce6/TPP) was developed for light-triggered ROS therapy. Driven by triphenylphosphine (TPP) moieties, selective accumulation of the nanoplatform within mitochondria was achieved. Upon single 660 nm laser irradiation, singlet oxygen (<sup>1</sup>O<sub>2</sub>) was generated by the photosensitizer Ce6 to execute the PDT effect, while the loaded copper ions catalyzed endogenous H<sub>2</sub>O<sub>2</sub> within tumor cells through a Fenton-like reaction, leading to in situ production of highly toxic hydroxyl radicals (•OH) to fulfill the CDT function. Additionally, mild photothermal effect (PTT) was produced by the graphene oxide scaffold, with a photothermal conversion efficiency of 22.48%, through which the Fenton-like reaction rate was thermodynamically accelerated, thereby achieving synergistic PTT–CDT enhancement. The combination of mitochondrial localization and mild hyperthermia triggered an amplified local ROS burst. In vitro cellular experiments demonstrated that, under 660 nm laser irradiation at 0.5 W/cm<sup>2</sup>, a tumor cell killing rate of 75.89% was achieved through PDT/CDT/PTT trimodal synergistic effects, and cancer cell apoptosis was significantly enhanced. Consequently, this work provides a novel strategy for precision cancer therapy by co-localizing ROS generation and mild hyperthermia at the most vulnerable subcellular site.</p>

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Mitochondria-targeted and 660 nm laser-triggered nanoplatform with mild photothermal effect for enhanced ROS-mediated therapy

  • 期刊论文

  • 发表日期：

    2026年5月21日

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  • Haoyu Luo,
  • Feng Liu,
  • Jiale Li,
  • Tao Wang,
  • Lianpeng Lv,
  • Bing Wang

摘要

Reactive oxygen species (ROS)-mediated therapeutic modalities, including photodynamic therapy (PDT) and copper ion-mediated chemodynamic therapy (CDT), have been recognized as highly promising non-invasive strategies for cancer treatment. However, their therapeutic efficacy is frequently restricted by poor subcellular targeting capability. To address this challenge, a mitochondria-targeted nanoplatform (Cu@GO-PEG-Ce6/TPP) was developed for light-triggered ROS therapy. Driven by triphenylphosphine (TPP) moieties, selective accumulation of the nanoplatform within mitochondria was achieved. Upon single 660 nm laser irradiation, singlet oxygen (1O2) was generated by the photosensitizer Ce6 to execute the PDT effect, while the loaded copper ions catalyzed endogenous H2O2 within tumor cells through a Fenton-like reaction, leading to in situ production of highly toxic hydroxyl radicals (•OH) to fulfill the CDT function. Additionally, mild photothermal effect (PTT) was produced by the graphene oxide scaffold, with a photothermal conversion efficiency of 22.48%, through which the Fenton-like reaction rate was thermodynamically accelerated, thereby achieving synergistic PTT–CDT enhancement. The combination of mitochondrial localization and mild hyperthermia triggered an amplified local ROS burst. In vitro cellular experiments demonstrated that, under 660 nm laser irradiation at 0.5 W/cm2, a tumor cell killing rate of 75.89% was achieved through PDT/CDT/PTT trimodal synergistic effects, and cancer cell apoptosis was significantly enhanced. Consequently, this work provides a novel strategy for precision cancer therapy by co-localizing ROS generation and mild hyperthermia at the most vulnerable subcellular site.