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<p>Conventional photothermal therapy (PTT) emphasizes elevating apparent temperature to hyperthermic levels, potentially causing severe adverse effects on normal tissues. Combining PTT with targeted protein degradation (TPD) technology may leverage exogenous light stimulation to achieve spatiotemporally controlled protein degradation, representing a promising strategy to enhance therapeutic specificity and efficacy. Estrogen receptor α (ERα), as a nuclear receptor and transcription factor, plays a central role in the initiation and progression of ER-positive breast cancer. Herein, we have constructed an ERα-targeting photothermal agent via the conjugation of an ERα ligand (designed based on Raloxifene) onto the gallium-based liquid metal nanodroplets (LMPF NPs), which may leverage superior ERα targetability and microscopic photothermal effect for effective photothermal-induced ERα protein degradation. The <i>in vitro</i> and <i>in vivo</i> studies have revealed that the biocompatible LMPF NPs can not only actively target ER-positive breast cancer cells, but also enable the controllable and highly specific target protein degradation upon mild near-infrared (NIR) laser activation, thereby exerting a potent anticancer effect to inhibit breast cancer progression. Collectively, this study demonstrates the potential of the photothermal-induced target protein degradation strategy based on the LM nanoplatform, offering a promising precision and highly efficient therapeutic modality for broader disease treatment.</p>

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Estrogen receptor α-targeting liquid metal nanoparticles for photothermal induced protein degradation

  • 期刊论文

  • 发表日期：

    2026年4月14日

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  • Yuxin Liu,
  • Huan He,
  • Xing Lu,
  • Wei Xu,
  • Luying Chen,
  • Ting He,
  • Hong Tan,
  • Zhengkai Wei,
  • Shuting He,
  • Jie Zhu,
  • Weidong Pan,
  • Chong Li,
  • Silong Zhang,
  • Wei Rao,
  • Dawei Wang

摘要

Conventional photothermal therapy (PTT) emphasizes elevating apparent temperature to hyperthermic levels, potentially causing severe adverse effects on normal tissues. Combining PTT with targeted protein degradation (TPD) technology may leverage exogenous light stimulation to achieve spatiotemporally controlled protein degradation, representing a promising strategy to enhance therapeutic specificity and efficacy. Estrogen receptor α (ERα), as a nuclear receptor and transcription factor, plays a central role in the initiation and progression of ER-positive breast cancer. Herein, we have constructed an ERα-targeting photothermal agent via the conjugation of an ERα ligand (designed based on Raloxifene) onto the gallium-based liquid metal nanodroplets (LMPF NPs), which may leverage superior ERα targetability and microscopic photothermal effect for effective photothermal-induced ERα protein degradation. The in vitro and in vivo studies have revealed that the biocompatible LMPF NPs can not only actively target ER-positive breast cancer cells, but also enable the controllable and highly specific target protein degradation upon mild near-infrared (NIR) laser activation, thereby exerting a potent anticancer effect to inhibit breast cancer progression. Collectively, this study demonstrates the potential of the photothermal-induced target protein degradation strategy based on the LM nanoplatform, offering a promising precision and highly efficient therapeutic modality for broader disease treatment.