Activation of pyroptosis by specific organelle-targeting photodynamic therapy to amplify immunogenic cell death for anti-tumor immunotherapy

Pyroptosis, a unique lytic programmed cell death, inspired tempting implications as potent anti-tumor strategy in pertinent to its potentials in stimulating anti-tumor immunity for eradication of primary tumors and metastasis. Nonetheless, rare therapeutics have been reported to successfully stimula...

Full description

Bibliographic Details
Main Authors: Shuang Zeng, Chen Chen, Liuwei Zhang, Xiaosheng Liu, Ming Qian, Hongyan Cui, Jingyun Wang, Qixian Chen, Xiaojun Peng
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2023-07-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X22003140
_version_ 1797861119952420864
author Shuang Zeng
Chen Chen
Liuwei Zhang
Xiaosheng Liu
Ming Qian
Hongyan Cui
Jingyun Wang
Qixian Chen
Xiaojun Peng
author_facet Shuang Zeng
Chen Chen
Liuwei Zhang
Xiaosheng Liu
Ming Qian
Hongyan Cui
Jingyun Wang
Qixian Chen
Xiaojun Peng
author_sort Shuang Zeng
collection DOAJ
description Pyroptosis, a unique lytic programmed cell death, inspired tempting implications as potent anti-tumor strategy in pertinent to its potentials in stimulating anti-tumor immunity for eradication of primary tumors and metastasis. Nonetheless, rare therapeutics have been reported to successfully stimulate pyroptosis. In view of the intimate participation of reactive oxygen species (ROS) in stimulating pyroptosis, we attempted to devise a spectrum of well-defined subcellular organelle (including mitochondria, lysosomes and endoplasmic reticulum)-targeting photosensitizers with the aim of precisely localizing ROS (produced from photosensitizers) at the subcellular compartments and explore their potentials in urging pyroptosis and immunogenic cell death (ICD). The subsequent investigations revealed varied degrees of pyroptosis upon photodynamic therapy (PDT) towards cancerous cells, as supported by not only observation of the distinctive morphological and mechanistic characteristics of pyroptosis, but for the first-time explicit validation from comprehensive RNA-Seq analysis. Furthermore, in vivo anti-tumor PDT could exert eradication of the primary tumors, more importantly suppressed the distant tumor and metastatic tumor growth through an abscopal effect, approving the acquirement of specific anti-tumor immunity as a consequence of pyroptosis. Hence, pyroptosis was concluded unprecedently by our proposed organelles-targeting PDT strategy and explicitly delineated with molecular insights into its occurrence and the consequent ICD.
first_indexed 2024-04-09T21:56:57Z
format Article
id doaj.art-f41c855265a54e5e842bc53ce4c0afec
institution Directory Open Access Journal
issn 2452-199X
language English
last_indexed 2024-04-09T21:56:57Z
publishDate 2023-07-01
publisher KeAi Communications Co., Ltd.
record_format Article
series Bioactive Materials
spelling doaj.art-f41c855265a54e5e842bc53ce4c0afec2023-03-24T04:23:01ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2023-07-0125580593Activation of pyroptosis by specific organelle-targeting photodynamic therapy to amplify immunogenic cell death for anti-tumor immunotherapyShuang Zeng0Chen Chen1Liuwei Zhang2Xiaosheng Liu3Ming Qian4Hongyan Cui5Jingyun Wang6Qixian Chen7Xiaojun Peng8School of Bioengineering, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, Dalian, 116024, ChinaState Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, Dalian, 116024, ChinaSchool of Bioengineering, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, Dalian, 116024, ChinaSchool of Bioengineering, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, Dalian, 116024, ChinaSchool of Bioengineering, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, Dalian, 116024, ChinaSchool of Bioengineering, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, Dalian, 116024, ChinaSchool of Bioengineering, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, Dalian, 116024, China; Corresponding author.School of Bioengineering, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, Dalian, 116024, China; Corresponding author.State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, Dalian, 116024, ChinaPyroptosis, a unique lytic programmed cell death, inspired tempting implications as potent anti-tumor strategy in pertinent to its potentials in stimulating anti-tumor immunity for eradication of primary tumors and metastasis. Nonetheless, rare therapeutics have been reported to successfully stimulate pyroptosis. In view of the intimate participation of reactive oxygen species (ROS) in stimulating pyroptosis, we attempted to devise a spectrum of well-defined subcellular organelle (including mitochondria, lysosomes and endoplasmic reticulum)-targeting photosensitizers with the aim of precisely localizing ROS (produced from photosensitizers) at the subcellular compartments and explore their potentials in urging pyroptosis and immunogenic cell death (ICD). The subsequent investigations revealed varied degrees of pyroptosis upon photodynamic therapy (PDT) towards cancerous cells, as supported by not only observation of the distinctive morphological and mechanistic characteristics of pyroptosis, but for the first-time explicit validation from comprehensive RNA-Seq analysis. Furthermore, in vivo anti-tumor PDT could exert eradication of the primary tumors, more importantly suppressed the distant tumor and metastatic tumor growth through an abscopal effect, approving the acquirement of specific anti-tumor immunity as a consequence of pyroptosis. Hence, pyroptosis was concluded unprecedently by our proposed organelles-targeting PDT strategy and explicitly delineated with molecular insights into its occurrence and the consequent ICD.http://www.sciencedirect.com/science/article/pii/S2452199X22003140PyroptosisTumorPhotodynamic therapyImmunogenic cell deathSubcellular targeting
spellingShingle Shuang Zeng
Chen Chen
Liuwei Zhang
Xiaosheng Liu
Ming Qian
Hongyan Cui
Jingyun Wang
Qixian Chen
Xiaojun Peng
Activation of pyroptosis by specific organelle-targeting photodynamic therapy to amplify immunogenic cell death for anti-tumor immunotherapy
Bioactive Materials
Pyroptosis
Tumor
Photodynamic therapy
Immunogenic cell death
Subcellular targeting
title Activation of pyroptosis by specific organelle-targeting photodynamic therapy to amplify immunogenic cell death for anti-tumor immunotherapy
title_full Activation of pyroptosis by specific organelle-targeting photodynamic therapy to amplify immunogenic cell death for anti-tumor immunotherapy
title_fullStr Activation of pyroptosis by specific organelle-targeting photodynamic therapy to amplify immunogenic cell death for anti-tumor immunotherapy
title_full_unstemmed Activation of pyroptosis by specific organelle-targeting photodynamic therapy to amplify immunogenic cell death for anti-tumor immunotherapy
title_short Activation of pyroptosis by specific organelle-targeting photodynamic therapy to amplify immunogenic cell death for anti-tumor immunotherapy
title_sort activation of pyroptosis by specific organelle targeting photodynamic therapy to amplify immunogenic cell death for anti tumor immunotherapy
topic Pyroptosis
Tumor
Photodynamic therapy
Immunogenic cell death
Subcellular targeting
url http://www.sciencedirect.com/science/article/pii/S2452199X22003140
work_keys_str_mv AT shuangzeng activationofpyroptosisbyspecificorganelletargetingphotodynamictherapytoamplifyimmunogeniccelldeathforantitumorimmunotherapy
AT chenchen activationofpyroptosisbyspecificorganelletargetingphotodynamictherapytoamplifyimmunogeniccelldeathforantitumorimmunotherapy
AT liuweizhang activationofpyroptosisbyspecificorganelletargetingphotodynamictherapytoamplifyimmunogeniccelldeathforantitumorimmunotherapy
AT xiaoshengliu activationofpyroptosisbyspecificorganelletargetingphotodynamictherapytoamplifyimmunogeniccelldeathforantitumorimmunotherapy
AT mingqian activationofpyroptosisbyspecificorganelletargetingphotodynamictherapytoamplifyimmunogeniccelldeathforantitumorimmunotherapy
AT hongyancui activationofpyroptosisbyspecificorganelletargetingphotodynamictherapytoamplifyimmunogeniccelldeathforantitumorimmunotherapy
AT jingyunwang activationofpyroptosisbyspecificorganelletargetingphotodynamictherapytoamplifyimmunogeniccelldeathforantitumorimmunotherapy
AT qixianchen activationofpyroptosisbyspecificorganelletargetingphotodynamictherapytoamplifyimmunogeniccelldeathforantitumorimmunotherapy
AT xiaojunpeng activationofpyroptosisbyspecificorganelletargetingphotodynamictherapytoamplifyimmunogeniccelldeathforantitumorimmunotherapy