Simultaneous Photoactivation of cGAS‐STING Pathway and Pyroptosis by Platinum(II) Triphenylamine Complexes for Cancer Immunotherapy

Activation of the cyclic GMP‐AMP synthase‐stimulator of the interferon gene (cGAS‐STING) pathway is a potent anticancer immunotherapeutic strategy, and the induction of pyroptosis is a feasible way to stimulate the anticancer immune responses. Herein, two PtII complexes (Pt1 and Pt2) were designed a...

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Published in	Angewandte Chemie International Edition Vol. 61; no. 43; pp. e202210988 - n/a
Main Authors	Ling, Yu‐Yi, Xia, Xiao‐Yu, Hao, Liang, Wang, Wen‐Jin, Zhang, Hang, Liu, Liu‐Yi, Liu, Wenting, Li, Zhi‐Yuan, Tan, Cai‐Ping, Mao, Zong‐Wan
Format	Journal Article
Language	English
Published	Germany Wiley Subscription Services, Inc 24.10.2022
Edition	International ed. in English
Subjects	Antiviral Agents - pharmacology Cancer immunotherapy cGAS-STING DNA - metabolism DNA Binding DNA damage Immune response Immune system Immunotherapy Interferon Interferons - pharmacology Irradiation Light effects Light irradiation Membrane Proteins - metabolism Mitochondrial DNA Neoplasms - therapy Nucleotidyltransferases - metabolism Photoactivation Photoimmunotherapy Platinum - pharmacology PtII Complexes Pyroptosis Radiation Radiation damage Signal Transduction Stimulators Photoimmunotherapy Pyroptosis PtII Complexes cGAS-STING DNA Binding
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Abstract	Activation of the cyclic GMP‐AMP synthase‐stimulator of the interferon gene (cGAS‐STING) pathway is a potent anticancer immunotherapeutic strategy, and the induction of pyroptosis is a feasible way to stimulate the anticancer immune responses. Herein, two PtII complexes (Pt1 and Pt2) were designed as photoactivators of the cGAS‐STING pathway. In response to light irradiation, Pt1 and Pt2 could damage mitochondrial/nuclear DNA and the nuclear envelope to activate the cGAS‐STING pathway, and concurrently induce pyroptosis in cancer cells, which evoked an intense anticancer immune response in vitro and in vivo. Overall, we present the first photoactivator of the cGAS‐STING pathway, which may provide an innovative design strategy for anticancer immunotherapy. The first small molecule that can activate cGAS‐STING in a photocontrollable way is reported. Upon irradiation, Pt1 and Pt2 can damage mitochondrial DNA, the nuclear envelope and nuclear DNA sequentially, which effectively releases DNA into cytoplasm to activate the cGAS‐STING pathway both in vitro and in vivo.
AbstractList	Activation of the cyclic GMP‐AMP synthase‐stimulator of the interferon gene (cGAS‐STING) pathway is a potent anticancer immunotherapeutic strategy, and the induction of pyroptosis is a feasible way to stimulate the anticancer immune responses. Herein, two PtII complexes (Pt1 and Pt2) were designed as photoactivators of the cGAS‐STING pathway. In response to light irradiation, Pt1 and Pt2 could damage mitochondrial/nuclear DNA and the nuclear envelope to activate the cGAS‐STING pathway, and concurrently induce pyroptosis in cancer cells, which evoked an intense anticancer immune response in vitro and in vivo. Overall, we present the first photoactivator of the cGAS‐STING pathway, which may provide an innovative design strategy for anticancer immunotherapy. The first small molecule that can activate cGAS‐STING in a photocontrollable way is reported. Upon irradiation, Pt1 and Pt2 can damage mitochondrial DNA, the nuclear envelope and nuclear DNA sequentially, which effectively releases DNA into cytoplasm to activate the cGAS‐STING pathway both in vitro and in vivo. Activation of the cyclic GMP‐AMP synthase‐stimulator of the interferon gene (cGAS‐STING) pathway is a potent anticancer immunotherapeutic strategy, and the induction of pyroptosis is a feasible way to stimulate the anticancer immune responses. Herein, two Pt II complexes ( Pt1 and Pt2 ) were designed as photoactivators of the cGAS‐STING pathway. In response to light irradiation, Pt1 and Pt2 could damage mitochondrial/nuclear DNA and the nuclear envelope to activate the cGAS‐STING pathway, and concurrently induce pyroptosis in cancer cells, which evoked an intense anticancer immune response in vitro and in vivo. Overall, we present the first photoactivator of the cGAS‐STING pathway, which may provide an innovative design strategy for anticancer immunotherapy. Activation of the cyclic GMP‐AMP synthase‐stimulator of the interferon gene (cGAS‐STING) pathway is a potent anticancer immunotherapeutic strategy, and the induction of pyroptosis is a feasible way to stimulate the anticancer immune responses. Herein, two PtII complexes (Pt1 and Pt2) were designed as photoactivators of the cGAS‐STING pathway. In response to light irradiation, Pt1 and Pt2 could damage mitochondrial/nuclear DNA and the nuclear envelope to activate the cGAS‐STING pathway, and concurrently induce pyroptosis in cancer cells, which evoked an intense anticancer immune response in vitro and in vivo. Overall, we present the first photoactivator of the cGAS‐STING pathway, which may provide an innovative design strategy for anticancer immunotherapy. Activation of the cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) pathway is a potent anticancer immunotherapeutic strategy, and the induction of pyroptosis is a feasible way to stimulate the anticancer immune responses. Herein, two PtII complexes (Pt1 and Pt2) were designed as photoactivators of the cGAS-STING pathway. In response to light irradiation, Pt1 and Pt2 could damage mitochondrial/nuclear DNA and the nuclear envelope to activate the cGAS-STING pathway, and concurrently induce pyroptosis in cancer cells, which evoked an intense anticancer immune response in vitro and in vivo. Overall, we present the first photoactivator of the cGAS-STING pathway, which may provide an innovative design strategy for anticancer immunotherapy.Activation of the cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) pathway is a potent anticancer immunotherapeutic strategy, and the induction of pyroptosis is a feasible way to stimulate the anticancer immune responses. Herein, two PtII complexes (Pt1 and Pt2) were designed as photoactivators of the cGAS-STING pathway. In response to light irradiation, Pt1 and Pt2 could damage mitochondrial/nuclear DNA and the nuclear envelope to activate the cGAS-STING pathway, and concurrently induce pyroptosis in cancer cells, which evoked an intense anticancer immune response in vitro and in vivo. Overall, we present the first photoactivator of the cGAS-STING pathway, which may provide an innovative design strategy for anticancer immunotherapy. Activation of the cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) pathway is a potent anticancer immunotherapeutic strategy, and the induction of pyroptosis is a feasible way to stimulate the anticancer immune responses. Herein, two Pt complexes (Pt1 and Pt2) were designed as photoactivators of the cGAS-STING pathway. In response to light irradiation, Pt1 and Pt2 could damage mitochondrial/nuclear DNA and the nuclear envelope to activate the cGAS-STING pathway, and concurrently induce pyroptosis in cancer cells, which evoked an intense anticancer immune response in vitro and in vivo. Overall, we present the first photoactivator of the cGAS-STING pathway, which may provide an innovative design strategy for anticancer immunotherapy.
Author	Mao, Zong‐Wan Wang, Wen‐Jin Tan, Cai‐Ping Xia, Xiao‐Yu Hao, Liang Zhang, Hang Ling, Yu‐Yi Liu, Wenting Li, Zhi‐Yuan Liu, Liu‐Yi
Author_xml	– sequence: 1 givenname: Yu‐Yi surname: Ling fullname: Ling, Yu‐Yi organization: Sun Yat-Sen University – sequence: 2 givenname: Xiao‐Yu surname: Xia fullname: Xia, Xiao‐Yu organization: Sun Yat-Sen University – sequence: 3 givenname: Liang surname: Hao fullname: Hao, Liang organization: Sun Yat-Sen University – sequence: 4 givenname: Wen‐Jin surname: Wang fullname: Wang, Wen‐Jin organization: Sun Yat-Sen University – sequence: 5 givenname: Hang surname: Zhang fullname: Zhang, Hang organization: Sun Yat-Sen University – sequence: 6 givenname: Liu‐Yi surname: Liu fullname: Liu, Liu‐Yi organization: Sun Yat-Sen University – sequence: 7 givenname: Wenting surname: Liu fullname: Liu, Wenting organization: Sun Yat-Sen University – sequence: 8 givenname: Zhi‐Yuan surname: Li fullname: Li, Zhi‐Yuan organization: Sun Yat-Sen University – sequence: 9 givenname: Cai‐Ping surname: Tan fullname: Tan, Cai‐Ping email: tancaip@mail.sysu.edu.cn organization: Sun Yat-Sen University – sequence: 10 givenname: Zong‐Wan orcidid: 0000-0001-7131-1154 surname: Mao fullname: Mao, Zong‐Wan email: cesmzw@mail.sysu.edu.cn organization: Sun Yat-Sen University
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Snippet	Activation of the cyclic GMP‐AMP synthase‐stimulator of the interferon gene (cGAS‐STING) pathway is a potent anticancer immunotherapeutic strategy, and the... Activation of the cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) pathway is a potent anticancer immunotherapeutic strategy, and the...
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SubjectTerms	Antiviral Agents - pharmacology Cancer immunotherapy cGAS-STING DNA - metabolism DNA Binding DNA damage Immune response Immune system Immunotherapy Interferon Interferons - pharmacology Irradiation Light effects Light irradiation Membrane Proteins - metabolism Mitochondrial DNA Neoplasms - therapy Nucleotidyltransferases - metabolism Photoactivation Photoimmunotherapy Platinum - pharmacology PtII Complexes Pyroptosis Radiation Radiation damage Signal Transduction Stimulators
Title	Simultaneous Photoactivation of cGAS‐STING Pathway and Pyroptosis by Platinum(II) Triphenylamine Complexes for Cancer Immunotherapy
URI	https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fanie.202210988 https://www.ncbi.nlm.nih.gov/pubmed/35979672 https://www.proquest.com/docview/2725704035 https://www.proquest.com/docview/2703984425
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