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Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma

Although RNA interference (RNAi) therapy has emerged as a potential tool in cancer therapeutics, the application of RNAi to glioblastoma (GBM) remains a hurdle. Herein, to improve the therapeutic effect of RNAi on GBM, a cancer cell membrane (CCM)-disguised hypoxia-triggered RNAi nanomedicine was de...

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Autores principales: Wang, Zhen, Tang, Xiang-long, Zhao, Meng-jie, Zhang, Yi-ding, Xiao, Yong, Liu, Yu-yang, Qian, Chun-fa, Xie, Yan-dong, Liu, Yong, Zou, Yuan-jie, Yang, Kun, Liu, Hong-yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10324258/
https://www.ncbi.nlm.nih.gov/pubmed/37408007
http://dx.doi.org/10.1186/s12951-023-01960-w
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author Wang, Zhen
Tang, Xiang-long
Zhao, Meng-jie
Zhang, Yi-ding
Xiao, Yong
Liu, Yu-yang
Qian, Chun-fa
Xie, Yan-dong
Liu, Yong
Zou, Yuan-jie
Yang, Kun
Liu, Hong-yi
author_facet Wang, Zhen
Tang, Xiang-long
Zhao, Meng-jie
Zhang, Yi-ding
Xiao, Yong
Liu, Yu-yang
Qian, Chun-fa
Xie, Yan-dong
Liu, Yong
Zou, Yuan-jie
Yang, Kun
Liu, Hong-yi
author_sort Wang, Zhen
collection PubMed
description Although RNA interference (RNAi) therapy has emerged as a potential tool in cancer therapeutics, the application of RNAi to glioblastoma (GBM) remains a hurdle. Herein, to improve the therapeutic effect of RNAi on GBM, a cancer cell membrane (CCM)-disguised hypoxia-triggered RNAi nanomedicine was developed for short interfering RNA (siRNA) delivery to sensitize cells to chemotherapy and radiotherapy. Our synthesized CCM-disguised RNAi nanomedicine showed prolonged blood circulation, high BBB transcytosis and specific accumulation in GBM sites via homotypic recognition. Disruption and effective anti-GBM agents were triggered in the hypoxic region, leading to efficient tumor suppression by using phosphoglycerate kinase 1 (PGK1) silencing to enhance paclitaxel-induced chemotherapy and sensitize hypoxic GBM cells to ionizing radiation. In summary, a biomimetic intelligent RNAi nanomedicine has been developed for siRNA delivery to synergistically mediate a combined chemo/radiotherapy that presents immune-free and hypoxia-triggered properties with high survival rates for orthotopic GBM treatment. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-023-01960-w.
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spelling pubmed-103242582023-07-07 Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma Wang, Zhen Tang, Xiang-long Zhao, Meng-jie Zhang, Yi-ding Xiao, Yong Liu, Yu-yang Qian, Chun-fa Xie, Yan-dong Liu, Yong Zou, Yuan-jie Yang, Kun Liu, Hong-yi J Nanobiotechnology Methodology Although RNA interference (RNAi) therapy has emerged as a potential tool in cancer therapeutics, the application of RNAi to glioblastoma (GBM) remains a hurdle. Herein, to improve the therapeutic effect of RNAi on GBM, a cancer cell membrane (CCM)-disguised hypoxia-triggered RNAi nanomedicine was developed for short interfering RNA (siRNA) delivery to sensitize cells to chemotherapy and radiotherapy. Our synthesized CCM-disguised RNAi nanomedicine showed prolonged blood circulation, high BBB transcytosis and specific accumulation in GBM sites via homotypic recognition. Disruption and effective anti-GBM agents were triggered in the hypoxic region, leading to efficient tumor suppression by using phosphoglycerate kinase 1 (PGK1) silencing to enhance paclitaxel-induced chemotherapy and sensitize hypoxic GBM cells to ionizing radiation. In summary, a biomimetic intelligent RNAi nanomedicine has been developed for siRNA delivery to synergistically mediate a combined chemo/radiotherapy that presents immune-free and hypoxia-triggered properties with high survival rates for orthotopic GBM treatment. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-023-01960-w. BioMed Central 2023-07-05 /pmc/articles/PMC10324258/ /pubmed/37408007 http://dx.doi.org/10.1186/s12951-023-01960-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Methodology
Wang, Zhen
Tang, Xiang-long
Zhao, Meng-jie
Zhang, Yi-ding
Xiao, Yong
Liu, Yu-yang
Qian, Chun-fa
Xie, Yan-dong
Liu, Yong
Zou, Yuan-jie
Yang, Kun
Liu, Hong-yi
Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma
title Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma
title_full Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma
title_fullStr Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma
title_full_unstemmed Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma
title_short Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma
title_sort biomimetic hypoxia-triggered rnai nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma
topic Methodology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10324258/
https://www.ncbi.nlm.nih.gov/pubmed/37408007
http://dx.doi.org/10.1186/s12951-023-01960-w
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