Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death

Abstract The immunogenicity of dying cancer cells determines the efficacy of anti-cancer therapy. Photodynamic therapy (PDT) can induce immunogenic cell death (ICD), which is characterized by the emission of damage-associated molecular patterns (DAMPs) from dying cells. This emission can trigger eff...

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Autores principales:	Victoria D. Turubanova, Tatiana A. Mishchenko, Irina V. Balalaeva, Iuliia Efimova, Nina N. Peskova, Larisa G. Klapshina, Svetlana A. Lermontova, Claus Bachert, Olga Krysko, Maria V. Vedunova, Dmitri V. Krysko
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/41e549963f9b4302b7339409a3df2132
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spelling	oai:doaj.org-article:41e549963f9b4302b7339409a3df21322021-12-02T18:18:06ZNovel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death10.1038/s41598-021-86354-42045-2322https://doaj.org/article/41e549963f9b4302b7339409a3df21322021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86354-4https://doaj.org/toc/2045-2322Abstract The immunogenicity of dying cancer cells determines the efficacy of anti-cancer therapy. Photodynamic therapy (PDT) can induce immunogenic cell death (ICD), which is characterized by the emission of damage-associated molecular patterns (DAMPs) from dying cells. This emission can trigger effective anti-tumor immunity. Only a few photosensitizers are known to induce ICD and, therefore, there is a need for development of new photosensitizers that can induce ICD. The purpose of this work was to analyze whether photosensitizers developed in-house from porphyrazines (pz I and pz III) can induce ICD in vitro and in vivo when used in PDT. We indetified the optimal concentrations of the photosensitizers and found that, at a light dose of 20 J/cm2 (λex 615–635 nm), both pz I and pz III efficiently induced cell death in cancer cells. We demonstrate that pz I localized predominantly in the Golgi apparatus and lysosomes while pz III in the endoplasmic reticulum and lysosomes. The cell death induced by pz I-PDT was inhibited by zVAD-fmk (apoptosis inhibitor) but not by ferrostatin-1 and DFO (ferroptosis inhibitors) or by necrostatin-1 s (necroptosis inhibitor). By contrast, the cell death induced by pz III-PDT was inhibited by z-VAD-fmk and by the necroptosis inhibitor, necrostatin-1 s. Cancer cells induced by pz I-PDT or pz III-PDT released HMGB1 and ATP and were engulfed by bone marrow-derived dendritic cells, which then matured and became activated in vitro. We demonstrate that cancer cells, after induction of cell death by pz I-PDT or pz III-PDT, are protective when used in the mouse model of prophylactic tumor vaccination. By vaccinating immunodeficient mice, we prove the role of the adaptive immune system in protecting against tumours. All together, we have shown that two novel porphyrazines developed in-house are potent ICD inducers that could be effectively applied in PDT of cancer.Victoria D. TurubanovaTatiana A. MishchenkoIrina V. BalalaevaIuliia EfimovaNina N. PeskovaLarisa G. KlapshinaSvetlana A. LermontovaClaus BachertOlga KryskoMaria V. VedunovaDmitri V. KryskoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Victoria D. Turubanova Tatiana A. Mishchenko Irina V. Balalaeva Iuliia Efimova Nina N. Peskova Larisa G. Klapshina Svetlana A. Lermontova Claus Bachert Olga Krysko Maria V. Vedunova Dmitri V. Krysko Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death
description	Abstract The immunogenicity of dying cancer cells determines the efficacy of anti-cancer therapy. Photodynamic therapy (PDT) can induce immunogenic cell death (ICD), which is characterized by the emission of damage-associated molecular patterns (DAMPs) from dying cells. This emission can trigger effective anti-tumor immunity. Only a few photosensitizers are known to induce ICD and, therefore, there is a need for development of new photosensitizers that can induce ICD. The purpose of this work was to analyze whether photosensitizers developed in-house from porphyrazines (pz I and pz III) can induce ICD in vitro and in vivo when used in PDT. We indetified the optimal concentrations of the photosensitizers and found that, at a light dose of 20 J/cm2 (λex 615–635 nm), both pz I and pz III efficiently induced cell death in cancer cells. We demonstrate that pz I localized predominantly in the Golgi apparatus and lysosomes while pz III in the endoplasmic reticulum and lysosomes. The cell death induced by pz I-PDT was inhibited by zVAD-fmk (apoptosis inhibitor) but not by ferrostatin-1 and DFO (ferroptosis inhibitors) or by necrostatin-1 s (necroptosis inhibitor). By contrast, the cell death induced by pz III-PDT was inhibited by z-VAD-fmk and by the necroptosis inhibitor, necrostatin-1 s. Cancer cells induced by pz I-PDT or pz III-PDT released HMGB1 and ATP and were engulfed by bone marrow-derived dendritic cells, which then matured and became activated in vitro. We demonstrate that cancer cells, after induction of cell death by pz I-PDT or pz III-PDT, are protective when used in the mouse model of prophylactic tumor vaccination. By vaccinating immunodeficient mice, we prove the role of the adaptive immune system in protecting against tumours. All together, we have shown that two novel porphyrazines developed in-house are potent ICD inducers that could be effectively applied in PDT of cancer.
format	article
author	Victoria D. Turubanova Tatiana A. Mishchenko Irina V. Balalaeva Iuliia Efimova Nina N. Peskova Larisa G. Klapshina Svetlana A. Lermontova Claus Bachert Olga Krysko Maria V. Vedunova Dmitri V. Krysko
author_facet	Victoria D. Turubanova Tatiana A. Mishchenko Irina V. Balalaeva Iuliia Efimova Nina N. Peskova Larisa G. Klapshina Svetlana A. Lermontova Claus Bachert Olga Krysko Maria V. Vedunova Dmitri V. Krysko
author_sort	Victoria D. Turubanova
title	Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death
title_short	Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death
title_full	Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death
title_fullStr	Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death
title_full_unstemmed	Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death
title_sort	novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/41e549963f9b4302b7339409a3df2132
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Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death

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