Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma
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Published:2023-07-05
Issue:1
Volume:21
Page:
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ISSN:1477-3155
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Container-title:Journal of Nanobiotechnology
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language:en
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Short-container-title:J Nanobiotechnol
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
Abstract
AbstractAlthough 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
Funder
Postgraduate Research & Practice Innovation Program the Medical Research Foundation of Jiangsu Health Commission the Medical Science and Technology Development Foundation of Nanjing the Science and Technology Development Foundation of Nanjing Medical University Jiangsu Province, the National Natural Science Foundation of China the Clinical Medical Special Program of Science and Technology Project of Jiangsu Province
Publisher
Springer Science and Business Media LLC
Subject
Pharmaceutical Science,Applied Microbiology and Biotechnology,Biomedical Engineering,Molecular Medicine,Medicine (miscellaneous),Bioengineering
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