NIR-715 photodynamic therapy induces immunogenic cancer cell death by enhancing the endoplasmic reticulum stress response

  • Cell Death Dis. 2024 Dec 18;15(12):890. doi: 10.1038/s41419-024-07283-4.
Zhen-Yuan Zheng  #  1  2  3 ,  Wan Lin  #  1  2 ,  Jia-Wan Su  #  4 ,  Qing-Feng Huang  1  2 ,  Cong Zhang  1  2 ,  Wen-Xing Pan  1  2 ,  En-Min Li  5 ,  He-Feng Zhang  #  6 ,  Li-Yan Xu  #  7  8  9
Affiliations
  • 1. Department of Oncobiology, Department of Basic Medical Sciences, Shantou University Medical College, Shantou, Guangdong, PR China.
  • 2. The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Cancer Research Center, Shantou University Medical College, Shantou, 515041, Guangdong, P. R. China.
  • 3. Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Shantou, China.
  • 4. Department of Chemistry and Key Laboratory for Preparation and Application of Ordered Structural Materials of Guangdong Province, Shantou University, Science Building, 243 Daxue Road, Shantou, 515063, Guangdong, PR China.
  • 5. The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, 515041, Guangdong, China.
  • 6. Department of Chemistry and Key Laboratory for Preparation and Application of Ordered Structural Materials of Guangdong Province, Shantou University, Science Building, 243 Daxue Road, Shantou, 515063, Guangdong, PR China. [email protected].
  • 7. Department of Oncobiology, Department of Basic Medical Sciences, Shantou University Medical College, Shantou, Guangdong, PR China. [email protected].
  • 8. The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Cancer Research Center, Shantou University Medical College, Shantou, 515041, Guangdong, P. R. China. [email protected].
  • 9. Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Shantou, China. [email protected].
  • # Contributed equally.
PMID: 39695072 DOI: 10.1038/s41419-024-07283-4
Abstract

Effectively interfering with endoplasmic reticulum (ER) function in tumor cells and simultaneously activating an anti-tumor immune microenvironment to attack the tumor cells are promising strategies for Cancer treatment. However, precise ER-stress induction is still a huge challenge. In this study, we synthesized a near-infrared (NIR) probe, NIR-715, which induces tumor cell death and inhibits tumor growth without causing apparent side effects. NIR-715 triggers severe ER stress and immunogenic cell death (ICD) after visible light exposure. NIR-715 induced ICD-associated HMGB1 release in vitro and anti-tumor immune responses, including increased cytotoxic T lymphocyte (GZMB+ CD8+ T cell) infiltration and decreased numbers of exhausted T lymphocytes (PD-L1+ CD8+ T cell). These findings suggest that NIR-715 may be a novel agent for "cold" tumor photodynamic therapy (PDT). Schematic illustration of NIR-715 photodynamic therapy for visible light-triggered, endoplasmic reticulum-targeting antitumor therapy.

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