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

IF 12.4 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Theranostics Pub Date : 2025-06-09 eCollection Date: 2025-01-01 DOI:10.7150/thno.111635
Yuqing Wang, Chuxing Chai, Wangxing Lin, Juanmei Cao, Zhuoxia Li, Yifan Jin, Yiting Xu, Jianyu Zhang, Yong Qu, Jinshan Zhan, Tianqi Zhao, Yufan Chen, Meng Gao, Changzheng Huang, Min Li
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引用次数: 0

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.

氧化应激介导的PANoptosis和ferroptosis:探索aie活性纳米光敏剂通过光动力疗法引发的多模式细胞死亡。
背景:基于聚集诱导发射(AIE)的光动力疗法(PDT)是一种很有前途的癌症治疗策略,因为它能够通过明显的氧化应激激活特定的细胞死亡途径。虽然特定死亡途径的激活与PDT效率和整体效果相关,但氧化应激在不同细胞死亡模式中的系统协调以增强治疗效果仍未被探索。目前的研究缺乏对氧化应激如何协调多种细胞死亡途径以增强PDT治疗效果的系统调查。方法:研制了一种基于ai的纳米光敏剂(T-T NPs),通过PDT诱导多模态细胞死亡。该系统的特点是线粒体靶向能力和活性氧(ROS)的产生。机制分析评估程序性细胞死亡途径和铁下垂诱导肿瘤。结果:T-T NPs表现出优越的线粒体靶向性和高效的ROS生成。这种双重作用成功地触发了PANoptosis和ferroptosis。这些途径的协同激活显著增强了pdt介导的抗肿瘤疗效。结论:我们的研究结果表明,aie驱动的PDT可以通过氧化应激调节肿瘤中的多模式细胞死亡。通过同时激活PANoptosis和ferroptosis,该方法为克服传统单途径靶向PDT的局限性建立了一种新的范例。
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来源期刊
Theranostics
Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
25.40
自引率
1.60%
发文量
433
审稿时长
1 months
期刊介绍: Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.
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