Scholarlink

<p>Success in systemic immunotherapy against metastatic cancer hinges on the ability to achieve tumour-specific immune activation over normal tissues. Single-gate stimuli-responsive systems are not adequate at differentiating tumour versus normal tissue signals. Here we report an AND-gated nanoparticle that requires acidic pH and hypoxia signals to activate the stimulator of interferon genes (STING) pathway in systemic therapy of metastatic cancers. The dual stimuli-responsive nanoparticle consists of a small-molecule STING agonist conjugated to a pH-sensitive polymer through a hypoxia-sensitive linker. Biochemical analyses confirmed the (pH–hypoxia) AND logic truth table in STING activation. The nanoparticle agonist significantly reduced metastatic burdens in multiple immune-cold tumour models while exhibiting minimal systemic toxicity. Mechanistic investigation revealed that STING activation in tumour-resident type I dendritic cells drives CD8<sup>+</sup> T cell priming and infiltration, which synergizes with immune checkpoint inhibitors. This AND logic nanoplatform offers a safe and efficacious therapeutic for STING-mediated immunotherapy against metastatic cancers.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

AND logic nanoparticle for precision immunotherapy of metastatic cancers

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月9日

查看全文
  • Shuyue Ye,
  • Shuang Chen,
  • Vijay Basava,
  • Katy Torres,
  • Yangyang Zhao,
  • Gang Huang,
  • Mingyi Chen,
  • Jinming Gao

摘要

Success in systemic immunotherapy against metastatic cancer hinges on the ability to achieve tumour-specific immune activation over normal tissues. Single-gate stimuli-responsive systems are not adequate at differentiating tumour versus normal tissue signals. Here we report an AND-gated nanoparticle that requires acidic pH and hypoxia signals to activate the stimulator of interferon genes (STING) pathway in systemic therapy of metastatic cancers. The dual stimuli-responsive nanoparticle consists of a small-molecule STING agonist conjugated to a pH-sensitive polymer through a hypoxia-sensitive linker. Biochemical analyses confirmed the (pH–hypoxia) AND logic truth table in STING activation. The nanoparticle agonist significantly reduced metastatic burdens in multiple immune-cold tumour models while exhibiting minimal systemic toxicity. Mechanistic investigation revealed that STING activation in tumour-resident type I dendritic cells drives CD8+ T cell priming and infiltration, which synergizes with immune checkpoint inhibitors. This AND logic nanoplatform offers a safe and efficacious therapeutic for STING-mediated immunotherapy against metastatic cancers.