Self-assembled RNA nanocarrier-mediated chemotherapy combined with molecular targeting in the treatment of esophageal squamous cell carcinoma

Abstract Background Esophageal cancer is the fifth most common cancer affecting men in China. The primary treatment options are surgery and traditional radio-chemotherapy; no effective targeted therapy exists yet. Self-assembled RNA nanocarriers are highly stable, easily functionally modified, and h...

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Autores principales:	Xiang Li, Li Zhang, Xiamei Guo, Fei Xie, Cheng Shen, Yali Jun, Chao Luo, Longfei Liu, Xiaojuan Yu, Zhengwei Zhang, Qilong Wang, Yong Gao, Keping Xu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	RNA nanoparticles Esophageal squamous cell carcinoma Target therapy miR-375 EGFR aptamer Biotechnology TP248.13-248.65 Medical technology R855-855.5
Acceso en línea:	https://doaj.org/article/a113fc3b069245c6be14a44381466490
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spelling	oai:doaj.org-article:a113fc3b069245c6be14a443814664902021-11-28T12:26:34ZSelf-assembled RNA nanocarrier-mediated chemotherapy combined with molecular targeting in the treatment of esophageal squamous cell carcinoma10.1186/s12951-021-01135-51477-3155https://doaj.org/article/a113fc3b069245c6be14a443814664902021-11-01T00:00:00Zhttps://doi.org/10.1186/s12951-021-01135-5https://doaj.org/toc/1477-3155Abstract Background Esophageal cancer is the fifth most common cancer affecting men in China. The primary treatment options are surgery and traditional radio-chemotherapy; no effective targeted therapy exists yet. Self-assembled RNA nanocarriers are highly stable, easily functionally modified, and have weak off-tumor targeting effects. Thus, they are among the most preferred carriers for mediating the targeted delivery of anti-tumor drugs. miR-375 was found to be significantly down-regulated in esophageal squamous cell carcinoma (ESCC) tissues and its overexpression effectively inhibits the proliferation, migration, and invasion of ESCC cells. Moreover, epidermal growth factor receptor (EGFR) was overexpressed in ESCC cells, and accumulation of RNA nanoparticles in ESCC tumors was enhanced by EGFR-specific aptamer (EGFRapt) modification. Results Herein, a novel four-way junction RNA nanocarrier, 4WJ-EGFRapt-miR-375-PTX simultaneously loaded with miR-375, PTX and decorated with EGFRapt, was developed. In vitro analysis demonstrated that 4WJ-EGFRapt-miR-375-PTX possesses strong thermal and pH stabilities. EGFRapt decoration facilitated tumor cell endocytosis and promoted deep penetration into 3D-ESCC spheroids. Xenograft mouse model for ESCC confirmed that 4WJ-EGFRapt-miR-375-PTX was selectively distributed in tumor sites via EGFRapt-mediating active targeting and targeted co-delivery of miR-375 and PTX exhibited more effective therapeutic efficacy with low systemic toxicity. Conclusion This strategy may provide a practical approach for targeted therapy of ESCC. Graphical AbstractXiang LiLi ZhangXiamei GuoFei XieCheng ShenYali JunChao LuoLongfei LiuXiaojuan YuZhengwei ZhangQilong WangYong GaoKeping XuBMCarticleRNA nanoparticlesEsophageal squamous cell carcinomaTarget therapymiR-375EGFR aptamerBiotechnologyTP248.13-248.65Medical technologyR855-855.5ENJournal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	RNA nanoparticles Esophageal squamous cell carcinoma Target therapy miR-375 EGFR aptamer Biotechnology TP248.13-248.65 Medical technology R855-855.5
spellingShingle	RNA nanoparticles Esophageal squamous cell carcinoma Target therapy miR-375 EGFR aptamer Biotechnology TP248.13-248.65 Medical technology R855-855.5 Xiang Li Li Zhang Xiamei Guo Fei Xie Cheng Shen Yali Jun Chao Luo Longfei Liu Xiaojuan Yu Zhengwei Zhang Qilong Wang Yong Gao Keping Xu Self-assembled RNA nanocarrier-mediated chemotherapy combined with molecular targeting in the treatment of esophageal squamous cell carcinoma
description	Abstract Background Esophageal cancer is the fifth most common cancer affecting men in China. The primary treatment options are surgery and traditional radio-chemotherapy; no effective targeted therapy exists yet. Self-assembled RNA nanocarriers are highly stable, easily functionally modified, and have weak off-tumor targeting effects. Thus, they are among the most preferred carriers for mediating the targeted delivery of anti-tumor drugs. miR-375 was found to be significantly down-regulated in esophageal squamous cell carcinoma (ESCC) tissues and its overexpression effectively inhibits the proliferation, migration, and invasion of ESCC cells. Moreover, epidermal growth factor receptor (EGFR) was overexpressed in ESCC cells, and accumulation of RNA nanoparticles in ESCC tumors was enhanced by EGFR-specific aptamer (EGFRapt) modification. Results Herein, a novel four-way junction RNA nanocarrier, 4WJ-EGFRapt-miR-375-PTX simultaneously loaded with miR-375, PTX and decorated with EGFRapt, was developed. In vitro analysis demonstrated that 4WJ-EGFRapt-miR-375-PTX possesses strong thermal and pH stabilities. EGFRapt decoration facilitated tumor cell endocytosis and promoted deep penetration into 3D-ESCC spheroids. Xenograft mouse model for ESCC confirmed that 4WJ-EGFRapt-miR-375-PTX was selectively distributed in tumor sites via EGFRapt-mediating active targeting and targeted co-delivery of miR-375 and PTX exhibited more effective therapeutic efficacy with low systemic toxicity. Conclusion This strategy may provide a practical approach for targeted therapy of ESCC. Graphical Abstract
format	article
author	Xiang Li Li Zhang Xiamei Guo Fei Xie Cheng Shen Yali Jun Chao Luo Longfei Liu Xiaojuan Yu Zhengwei Zhang Qilong Wang Yong Gao Keping Xu
author_facet	Xiang Li Li Zhang Xiamei Guo Fei Xie Cheng Shen Yali Jun Chao Luo Longfei Liu Xiaojuan Yu Zhengwei Zhang Qilong Wang Yong Gao Keping Xu
author_sort	Xiang Li
title	Self-assembled RNA nanocarrier-mediated chemotherapy combined with molecular targeting in the treatment of esophageal squamous cell carcinoma
title_short	Self-assembled RNA nanocarrier-mediated chemotherapy combined with molecular targeting in the treatment of esophageal squamous cell carcinoma
title_full	Self-assembled RNA nanocarrier-mediated chemotherapy combined with molecular targeting in the treatment of esophageal squamous cell carcinoma
title_fullStr	Self-assembled RNA nanocarrier-mediated chemotherapy combined with molecular targeting in the treatment of esophageal squamous cell carcinoma
title_full_unstemmed	Self-assembled RNA nanocarrier-mediated chemotherapy combined with molecular targeting in the treatment of esophageal squamous cell carcinoma
title_sort	self-assembled rna nanocarrier-mediated chemotherapy combined with molecular targeting in the treatment of esophageal squamous cell carcinoma
publisher	BMC
publishDate	2021
url	https://doaj.org/article/a113fc3b069245c6be14a44381466490
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Self-assembled RNA nanocarrier-mediated chemotherapy combined with molecular targeting in the treatment of esophageal squamous cell carcinoma

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