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<p>Effective treatment of non-small cell lung cancer (NSCLC) remains challenging due to its immunosuppressive tumor microenvironment, metabolic adaptability, and resistance to conventional therapies. To improve the treatment efficiency of NSCLC, we developed a multifunctional apigenin based nanoplatform (MAFE) for synergistic NSCLC therapy. Apigenin, a natural flavonoid with glycolysis inhibitory activity, coordinates with Fe³⁺ to form a metal-phenolic network coating on mesoporous silica nanoparticles, while a dual-organelle targeting photosensitizer was encapsulated within the mesopores. Upon 635&#xa0;nm laser irradiation, the organelle targeting photosensitizer induces photodynamic disruption of mitochondria and the endoplasmic reticulum, leading to mitochondrial membrane potential collapse and endoplasmic reticulum stress. Meanwhile, apigenin suppresses glycolysis and lactate production, thereby remodeling the immunosuppressive tumor microenvironment. The combined organelle perturbation and metabolic inhibition trigger damage associated molecular patterns release and immunogenic cell death, ultimately activating systemic antitumor immunity. In NSCLC mice, MAFE achieves tumor inhibition rates of 97% for primary tumors and 80% for distant tumors, accompanied by enhanced apigenin bioavailability, effective metabolic reprogramming, and increased effector T-cell infiltration. This work highlights a promising nanoplatform strategy integrating natural product based metabolic regulation with organelle targeting photodynamic therapy for advanced NSCLC immunotherapy.</p> Graphical abstract <p></p>

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Apigenin based nanoplatform achieves non-small cell lung cancer immunotherapy through glycolysis inhibition and photodynamic co-perturbation of organelles

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月9日

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  • Guoyang Zhang,
  • Guanghui Zhu,
  • Wei Yan,
  • Xuelei Chu,
  • Yuting Sun,
  • Tianyu Shao,
  • Xiaoming Jin,
  • Manman Xu,
  • Jie Li

摘要

Effective treatment of non-small cell lung cancer (NSCLC) remains challenging due to its immunosuppressive tumor microenvironment, metabolic adaptability, and resistance to conventional therapies. To improve the treatment efficiency of NSCLC, we developed a multifunctional apigenin based nanoplatform (MAFE) for synergistic NSCLC therapy. Apigenin, a natural flavonoid with glycolysis inhibitory activity, coordinates with Fe³⁺ to form a metal-phenolic network coating on mesoporous silica nanoparticles, while a dual-organelle targeting photosensitizer was encapsulated within the mesopores. Upon 635 nm laser irradiation, the organelle targeting photosensitizer induces photodynamic disruption of mitochondria and the endoplasmic reticulum, leading to mitochondrial membrane potential collapse and endoplasmic reticulum stress. Meanwhile, apigenin suppresses glycolysis and lactate production, thereby remodeling the immunosuppressive tumor microenvironment. The combined organelle perturbation and metabolic inhibition trigger damage associated molecular patterns release and immunogenic cell death, ultimately activating systemic antitumor immunity. In NSCLC mice, MAFE achieves tumor inhibition rates of 97% for primary tumors and 80% for distant tumors, accompanied by enhanced apigenin bioavailability, effective metabolic reprogramming, and increased effector T-cell infiltration. This work highlights a promising nanoplatform strategy integrating natural product based metabolic regulation with organelle targeting photodynamic therapy for advanced NSCLC immunotherapy.

Graphical abstract