2. Academic Validation
  3. Oxidative stress-mediated PANoptosis and ferroptosis: Exploration of multimodal cell death triggered by an AIE-active nano-photosensitizer via photodynamic therapy

Oxidative stress-mediated PANoptosis and ferroptosis: Exploration of multimodal cell death triggered by an AIE-active nano-photosensitizer via photodynamic therapy

  • Theranostics. 2025 Jun 9;15(14):6665-6685. doi: 10.7150/thno.111635.
Yuqing Wang 1,  Chuxing Chai 2,  Wangxing Lin 3,  Juanmei Cao 1 4,  Zhuoxia Li 2,  Yifan Jin 1,  Yiting Xu 5,  Jianyu Zhang 6,  Yong Qu 2,  Jinshan Zhan 1,  Tianqi Zhao 1,  Yufan Chen 1,  Meng Gao 3,  Changzheng Huang 1,  Min Li 2
Affiliations

Affiliations

  • 1 Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.; Department of Clinical Nutrition, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  • 2 Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  • 3 National Engineering Research Center for Tissue Restoration and Reconstruction, Key Laboratory of Biomedical Engineering of Guangdong Province, Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, Innovation Center for Tissue Restoration and Reconstruction, School of Materials Science and Engineering, South China University of Technology, Guangzhou 510006, China.
  • 4 Department of Dermatology, First Affiliated Hospital, Shihezi University, Shihezi 832008, China.
  • 5 Central Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  • 6 Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Hong Kong 999077, China.
PMID: 40585993 DOI: 10.7150/thno.111635
Abstract

Background: Aggregation-induced emission (AIE)-based photodynamic therapy (PDT) represents a promising strategy for Cancer treatment for its capacity to activate specific cell death pathways through pronounced oxidative stress. While the activation of specific death pathways has been correlated with PDT efficiency and overall effect, the systematic coordination of oxidative stress across different cell death modalities to amplify therapeutic effects remains unexplored. Current research lacks systematic investigation into how oxidative stress coordinates multiple cell death pathways to amplify therapeutic outcomes of PDT. Methods: We developed an AIE-based nano-photosensitizer (T-T NPs) to induce multimodal cell death through PDT. The system was characterized for mitochondrial targeting capability and Reactive Oxygen Species (ROS) generation. Mechanistic analyses were conducted to evaluate programmed cell death pathways and Ferroptosis induction in tumor. Results: T-T NPs exhibited superior mitochondrial targeting and highly efficient ROS generation. This dual effect successfully triggered PANoptosis and Ferroptosis. The synergistic activation of these pathways significantly enhanced PDT-mediated antitumor efficacy. Conclusion: Our findings reveal that AIE-driven PDT can orchestrate multimodal cell death in tumor through oxidative stress modulation. By concurrently activating PANoptosis and Ferroptosis, this approach establishes a novel paradigm for overcoming limitations of conventional single-pathway targeted PDT.

Keywords

Aggregation-induced emission; Ferroptosis; Oxidative stress; PANoptosis; Photodynamic therapy.

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