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Immunogenic Cell Death Induced by Chemoradiotherapy of Novel pH-Sensitive Cargo-Loaded Polymersomes in Glioblastoma
BACKGROUND: Inducing the immunogenic cell death of tumour cells can mediate the occurrence of antitumour immune responses and make the therapeutic effect more significant. Therefore, the development of treatments that can induce ICD to destroy tumour cells most effectively is promising. Previously,...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547843/ https://www.ncbi.nlm.nih.gov/pubmed/34712045 http://dx.doi.org/10.2147/IJN.S333197 |
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author | He, Chen Ding, Huiyan Chen, Jing Ding, Yinan Yang, Rui Hu, Chunmei An, Yanli Liu, Dongfang Liu, Peidang Tang, Qiusha Zhang, Zhiyuan |
author_facet | He, Chen Ding, Huiyan Chen, Jing Ding, Yinan Yang, Rui Hu, Chunmei An, Yanli Liu, Dongfang Liu, Peidang Tang, Qiusha Zhang, Zhiyuan |
author_sort | He, Chen |
collection | PubMed |
description | BACKGROUND: Inducing the immunogenic cell death of tumour cells can mediate the occurrence of antitumour immune responses and make the therapeutic effect more significant. Therefore, the development of treatments that can induce ICD to destroy tumour cells most effectively is promising. Previously, a new type of pH-sensitive polymersome was designed for the treatment of glioblastoma which represents a promising nanoplatform for future translational research in glioblastoma therapy. In this study, the aim of this work was to analyse whether chemoradiotherapy of the novel pH-sensitive cargo-loaded polymersomes can induce ICD. METHODS: Cell death in U87-MG and G422 cells was induced by Au-DOX@PO-ANG, and cell death was analysed by CCK-8 and flow cytometry. The release of CRT was determined by using laser scanning confocal microscopy and flow cytometry. ELISA kits were used to detect the release of HMGB1 and ATP. The dying cancer cells treated with different treatments were cocultured with bone-marrow-derived dendritic cells (BMDCs), and then flow cytometry was used to determine the maturation rate of BMDCs (CD11c+CD86+CD80+) to analyse the in vitro immunogenicity. Tumour vaccination experiments were used to evaluate the ability of Au-DOX@PO-ANG to induce ICD in vivo. RESULTS: We determined the optimal treatment strategy to evaluate the ability of chemotherapy combined with radiotherapy to induce ICD and dying cancer cells induced by Au-DOX@PO-ANG+RT could induce calreticulin eversion to the cell membrane, promote the release of HMGB1 and ATP, and induce the maturation of BMDCs. Using dying cancer cells induced by Au-DOX@PO-ANG+RT, we demonstrate the efficient vaccination potential of ICD in vivo. CONCLUSION: These results identify Au-DOX@PO-ANG as a novel immunogenic cell death inducer in vitro and in vivo that could be effectively combined with RT in cancer therapy. |
format | Online Article Text |
id | pubmed-8547843 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-85478432021-10-27 Immunogenic Cell Death Induced by Chemoradiotherapy of Novel pH-Sensitive Cargo-Loaded Polymersomes in Glioblastoma He, Chen Ding, Huiyan Chen, Jing Ding, Yinan Yang, Rui Hu, Chunmei An, Yanli Liu, Dongfang Liu, Peidang Tang, Qiusha Zhang, Zhiyuan Int J Nanomedicine Original Research BACKGROUND: Inducing the immunogenic cell death of tumour cells can mediate the occurrence of antitumour immune responses and make the therapeutic effect more significant. Therefore, the development of treatments that can induce ICD to destroy tumour cells most effectively is promising. Previously, a new type of pH-sensitive polymersome was designed for the treatment of glioblastoma which represents a promising nanoplatform for future translational research in glioblastoma therapy. In this study, the aim of this work was to analyse whether chemoradiotherapy of the novel pH-sensitive cargo-loaded polymersomes can induce ICD. METHODS: Cell death in U87-MG and G422 cells was induced by Au-DOX@PO-ANG, and cell death was analysed by CCK-8 and flow cytometry. The release of CRT was determined by using laser scanning confocal microscopy and flow cytometry. ELISA kits were used to detect the release of HMGB1 and ATP. The dying cancer cells treated with different treatments were cocultured with bone-marrow-derived dendritic cells (BMDCs), and then flow cytometry was used to determine the maturation rate of BMDCs (CD11c+CD86+CD80+) to analyse the in vitro immunogenicity. Tumour vaccination experiments were used to evaluate the ability of Au-DOX@PO-ANG to induce ICD in vivo. RESULTS: We determined the optimal treatment strategy to evaluate the ability of chemotherapy combined with radiotherapy to induce ICD and dying cancer cells induced by Au-DOX@PO-ANG+RT could induce calreticulin eversion to the cell membrane, promote the release of HMGB1 and ATP, and induce the maturation of BMDCs. Using dying cancer cells induced by Au-DOX@PO-ANG+RT, we demonstrate the efficient vaccination potential of ICD in vivo. CONCLUSION: These results identify Au-DOX@PO-ANG as a novel immunogenic cell death inducer in vitro and in vivo that could be effectively combined with RT in cancer therapy. Dove 2021-10-22 /pmc/articles/PMC8547843/ /pubmed/34712045 http://dx.doi.org/10.2147/IJN.S333197 Text en © 2021 He et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research He, Chen Ding, Huiyan Chen, Jing Ding, Yinan Yang, Rui Hu, Chunmei An, Yanli Liu, Dongfang Liu, Peidang Tang, Qiusha Zhang, Zhiyuan Immunogenic Cell Death Induced by Chemoradiotherapy of Novel pH-Sensitive Cargo-Loaded Polymersomes in Glioblastoma |
title | Immunogenic Cell Death Induced by Chemoradiotherapy of Novel pH-Sensitive Cargo-Loaded Polymersomes in Glioblastoma |
title_full | Immunogenic Cell Death Induced by Chemoradiotherapy of Novel pH-Sensitive Cargo-Loaded Polymersomes in Glioblastoma |
title_fullStr | Immunogenic Cell Death Induced by Chemoradiotherapy of Novel pH-Sensitive Cargo-Loaded Polymersomes in Glioblastoma |
title_full_unstemmed | Immunogenic Cell Death Induced by Chemoradiotherapy of Novel pH-Sensitive Cargo-Loaded Polymersomes in Glioblastoma |
title_short | Immunogenic Cell Death Induced by Chemoradiotherapy of Novel pH-Sensitive Cargo-Loaded Polymersomes in Glioblastoma |
title_sort | immunogenic cell death induced by chemoradiotherapy of novel ph-sensitive cargo-loaded polymersomes in glioblastoma |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547843/ https://www.ncbi.nlm.nih.gov/pubmed/34712045 http://dx.doi.org/10.2147/IJN.S333197 |
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