Liposomal chlorin e6-mediated photodynamic therapy induces cell pyroptosis and promotes anti-tumor immune effects in breast cancer

IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of photochemistry and photobiology. B, Biology Pub Date : 2024-10-29 DOI:10.1016/j.jphotobiol.2024.113047
Fang Yang , Song Zhang , Xiao Zhang , Chenchen Xu , Xiaoying Hou , Jinting Shang , Binlian Sun , Xiji Shu , Yuchen Liu , Yixiang Li , Haiping Wang
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Abstract

Pyroptosis is a form of inflammatory cell death that has been demonstrated to trigger anti-tumor immune responses. Photodynamic therapy (PDT) is an innovative non-invasive treatment for tumors that effectively destroys tumor cells and boosts anti-tumor immune response. The ability of PDT to trigger pyroptosis and its mechanism of action are yet uncertain. In this study, we firstly verified that PDT effectively eliminates tumor cells. TEM and Western blot analysis demonstrated that tumor cells underwent pyroptosis following PDT therapy. Lipo-Ce6 mostly accumulates in the mitochondria of 4 T1 cells, and abundant ROS generated during PDT severely damage cell mitochondria, leading to the release of mitochondrial DNA, triggering the inflammasome caspase-1 signaling cascade, and ultimately causing cell pyroptosis, in addition NAC (a scavenger of ROS) and EB (a scavenger of mitochondrial DNA) can effectively prevent cell pyroptosis by PDT, which indicated the key role of ROS in PDT induced pyroptosis. Moreover, we also found PDT tiggered immunogenic cell death (ICD). Fourthermore, PDT can efficiently suppress tumor growth, trigger ICD and induce cell pyroptosis in mice. The introducing of immune checkpoint inhibitor BMS202 significantly boosts the tumor inhibition rate and promotes the infiltration of immune cells into the tumor. The body weight and HE.
staining of normal organs primarily indicated the safety of this combined strategy. Our study demonstrated that PDT induced cell pyroptosis through mitochondrial oxidative damage and PDT induced pyroptosis effectively boost anti-cancer immunity, the combination of PDT and immune checkpoint inhibitor may be a promising clinical tumor treatment approaches.

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氯素e6脂质体介导的光动力疗法可诱导乳腺癌细胞发生热休克并促进抗肿瘤免疫效应。
热休克是一种炎性细胞死亡形式,已被证实能引发抗肿瘤免疫反应。光动力疗法(PDT)是一种创新的非侵入性肿瘤治疗方法,可有效摧毁肿瘤细胞并增强抗肿瘤免疫反应。目前,光动力疗法引发热蛋白沉积的能力及其作用机制尚不明确。在本研究中,我们首先验证了光动力疗法能有效消灭肿瘤细胞。TEM和Western印迹分析表明,PDT治疗后肿瘤细胞发生了热解。脂质-Ce6主要积聚在4 T1细胞的线粒体中,PDT过程中产生的大量ROS严重破坏了细胞线粒体,导致线粒体DNA释放,引发炎性体caspase-1信号级联,最终导致细胞热解、此外,NAC(ROS 的清除剂)和 EB(线粒体 DNA 的清除剂)也能有效防止 PDT 引起的细胞猝灭,这表明 ROS 在 PDT 诱导的细胞猝灭中起着关键作用。此外,我们还发现 PDT 会引发免疫性细胞死亡(ICD)。此外,PDT 还能有效抑制小鼠肿瘤的生长、引发 ICD 和诱导细胞热解。引入免疫检查点抑制剂 BMS202 能显著提高肿瘤抑制率,促进免疫细胞向肿瘤浸润。体重和正常器官的 HE 染色主要表明了这种联合策略的安全性。我们的研究表明,PDT通过线粒体氧化损伤诱导细胞热休克,PDT诱导的热休克能有效提高抗癌免疫力,PDT与免疫检查点抑制剂的联合应用可能是一种很有前景的临床肿瘤治疗方法。
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来源期刊
CiteScore
12.10
自引率
1.90%
发文量
161
审稿时长
37 days
期刊介绍: The Journal of Photochemistry and Photobiology B: Biology provides a forum for the publication of papers relating to the various aspects of photobiology, as well as a means for communication in this multidisciplinary field. The scope includes: - Bioluminescence - Chronobiology - DNA repair - Environmental photobiology - Nanotechnology in photobiology - Photocarcinogenesis - Photochemistry of biomolecules - Photodynamic therapy - Photomedicine - Photomorphogenesis - Photomovement - Photoreception - Photosensitization - Photosynthesis - Phototechnology - Spectroscopy of biological systems - UV and visible radiation effects and vision.
期刊最新文献
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