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<p>The stimulator of interferon genes (STING) pathway is a promising target in cancer immunotherapy. However, current nanomedicine strategies targeting the STING pathway often suffer from limited tumor specificity and insufficient immune activation. In this study, we developed a novel imaging-guided, self-amplifying photo-immunotherapeutic nanoparticle (SSCOL), comprising a liposome framework that encapsulates the phase-change material perfluoropentane (PFP), the photothermal agent superparamagnetic iron oxide (SPIO), and the STING agonist cGAMP. This nanoparticle exhibits excellent photoacoustic/ultrasound dual-modal imaging capability, enabling precise visualization of tumor tissue. CREKA enables specific binding to fibrin–fibronectin complexes in the tumor stroma, while NIR-induced photothermal effects of SPIO trigger coagulation, amplifying target formation and enhancing nanoparticle accumulation via a positive feedback mechanism. Under photothermal therapy, the phase transition of SSCOL enables the controlled and efficient release of the encapsulated cGAMP, which subsequently activates the STING pathway and triggers a pro-inflammatory cascade, enhances dendritic cell maturation and cytotoxic T lymphocyte activation, and elicits robust immune responses against both primary and metastatic tumors. Collectively, this multifunctional nanoparticle offers a promising strategy that integrates imaging, targeting, and photothermal-enhanced immune activation for STING-mediated cancer immunotherapy.</p> Graphical abstract <p></p>

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An imaging-guided self-amplifying photo-immunotherapeutic nanoparticle for STING pathway activation and enhanced cancer therapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月21日

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  • Qiaoqi Chen,
  • Huilin Yu,
  • Lin Li,
  • Hua Zhang,
  • Mixiao Tan,
  • Weiwei Liu,
  • Min Zheng,
  • Yaqin Hu,
  • Long Cheng,
  • Yushi Chen,
  • Haitao Ran,
  • Qiu Zeng,
  • Yuan Guo

摘要

The stimulator of interferon genes (STING) pathway is a promising target in cancer immunotherapy. However, current nanomedicine strategies targeting the STING pathway often suffer from limited tumor specificity and insufficient immune activation. In this study, we developed a novel imaging-guided, self-amplifying photo-immunotherapeutic nanoparticle (SSCOL), comprising a liposome framework that encapsulates the phase-change material perfluoropentane (PFP), the photothermal agent superparamagnetic iron oxide (SPIO), and the STING agonist cGAMP. This nanoparticle exhibits excellent photoacoustic/ultrasound dual-modal imaging capability, enabling precise visualization of tumor tissue. CREKA enables specific binding to fibrin–fibronectin complexes in the tumor stroma, while NIR-induced photothermal effects of SPIO trigger coagulation, amplifying target formation and enhancing nanoparticle accumulation via a positive feedback mechanism. Under photothermal therapy, the phase transition of SSCOL enables the controlled and efficient release of the encapsulated cGAMP, which subsequently activates the STING pathway and triggers a pro-inflammatory cascade, enhances dendritic cell maturation and cytotoxic T lymphocyte activation, and elicits robust immune responses against both primary and metastatic tumors. Collectively, this multifunctional nanoparticle offers a promising strategy that integrates imaging, targeting, and photothermal-enhanced immune activation for STING-mediated cancer immunotherapy.

Graphical abstract