Intelligent Bio-Responsive Fluorescent Au–shRNA Complexes for Regulated Autophagy and Effective Cancer Bioimaging and Therapeutics

The long non-coding RNA (lncRNA) MALAT1 acts as an oncogene. RNA interference (RNAi) is an effective method to control the expression of specific genes and can be used for the treatment of tumors, but an effective and safe carrier system is a significant obstacle to gene therapy. Herein, we explored...

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Autores principales:	Weijuan Cai, Liang Yin, Hui Jiang, Yossi Weizmann, Xuemei Wang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	bio-responsive fluorescent complexes shRNA delivery LncRNA MALAT1 cancer cells bioimaging therapeutics autophagy Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/f742f6f753174aa6b3f240643c5a7f7b
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spelling	oai:doaj.org-article:f742f6f753174aa6b3f240643c5a7f7b2021-11-25T16:55:02ZIntelligent Bio-Responsive Fluorescent Au–shRNA Complexes for Regulated Autophagy and Effective Cancer Bioimaging and Therapeutics10.3390/bios111104252079-6374https://doaj.org/article/f742f6f753174aa6b3f240643c5a7f7b2021-10-01T00:00:00Zhttps://www.mdpi.com/2079-6374/11/11/425https://doaj.org/toc/2079-6374The long non-coding RNA (lncRNA) MALAT1 acts as an oncogene. RNA interference (RNAi) is an effective method to control the expression of specific genes and can be used for the treatment of tumors, but an effective and safe carrier system is a significant obstacle to gene therapy. Herein, we explored the possibility of constructing an in situ bio-responsive self-assembled fluorescent gold-short hairpin RNA nanocomplex (Au–shRNA NCs) delivery system by co-incubating gold and MALAT1-shRNA for precise hepatocellular carcinoma (HCC) imaging and treatment. Due to the characteristics of the cancer microenvironment, Au–shRNA NCs self-assembled in HCC cells (HepG2) but did not occur in control cells (L02) under the same conditions. The in situ bio-responsive self-assembled Au–shRNA NCs delivery system can realize cancer cell bioimaging and promote cell uptake and endosomal escape mechanism, thereby realizing effective transfection. They effectively silenced target gene MALAT1, and with the downregulation of MALAT1, we found that several molecules involved in autophagic flux were also regulated. In vitro and tumor-bearing mouse model experiments demonstrated that the as-prepared fluorescent Au–shRNA NCs can readily realize tumor bioimaging and effectively silence the target gene MALAT1, and those autophagy-related pathway molecules were significantly downregulated, thereby exerting a tumor suppressor efficiency. This raises the possibility of realizing accurate multi-scale bio-imaging from the molecular-level with targeted gene-recognition to cancer cell imaging as well as in vivo tumor tissue imaging for the simultaneous precise cancer therapy.Weijuan CaiLiang YinHui JiangYossi WeizmannXuemei WangMDPI AGarticlebio-responsive fluorescent complexesshRNA deliveryLncRNA MALAT1cancer cells bioimagingtherapeuticsautophagyBiotechnologyTP248.13-248.65ENBiosensors, Vol 11, Iss 425, p 425 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bio-responsive fluorescent complexes shRNA delivery LncRNA MALAT1 cancer cells bioimaging therapeutics autophagy Biotechnology TP248.13-248.65
spellingShingle	bio-responsive fluorescent complexes shRNA delivery LncRNA MALAT1 cancer cells bioimaging therapeutics autophagy Biotechnology TP248.13-248.65 Weijuan Cai Liang Yin Hui Jiang Yossi Weizmann Xuemei Wang Intelligent Bio-Responsive Fluorescent Au–shRNA Complexes for Regulated Autophagy and Effective Cancer Bioimaging and Therapeutics
description	The long non-coding RNA (lncRNA) MALAT1 acts as an oncogene. RNA interference (RNAi) is an effective method to control the expression of specific genes and can be used for the treatment of tumors, but an effective and safe carrier system is a significant obstacle to gene therapy. Herein, we explored the possibility of constructing an in situ bio-responsive self-assembled fluorescent gold-short hairpin RNA nanocomplex (Au–shRNA NCs) delivery system by co-incubating gold and MALAT1-shRNA for precise hepatocellular carcinoma (HCC) imaging and treatment. Due to the characteristics of the cancer microenvironment, Au–shRNA NCs self-assembled in HCC cells (HepG2) but did not occur in control cells (L02) under the same conditions. The in situ bio-responsive self-assembled Au–shRNA NCs delivery system can realize cancer cell bioimaging and promote cell uptake and endosomal escape mechanism, thereby realizing effective transfection. They effectively silenced target gene MALAT1, and with the downregulation of MALAT1, we found that several molecules involved in autophagic flux were also regulated. In vitro and tumor-bearing mouse model experiments demonstrated that the as-prepared fluorescent Au–shRNA NCs can readily realize tumor bioimaging and effectively silence the target gene MALAT1, and those autophagy-related pathway molecules were significantly downregulated, thereby exerting a tumor suppressor efficiency. This raises the possibility of realizing accurate multi-scale bio-imaging from the molecular-level with targeted gene-recognition to cancer cell imaging as well as in vivo tumor tissue imaging for the simultaneous precise cancer therapy.
format	article
author	Weijuan Cai Liang Yin Hui Jiang Yossi Weizmann Xuemei Wang
author_facet	Weijuan Cai Liang Yin Hui Jiang Yossi Weizmann Xuemei Wang
author_sort	Weijuan Cai
title	Intelligent Bio-Responsive Fluorescent Au–shRNA Complexes for Regulated Autophagy and Effective Cancer Bioimaging and Therapeutics
title_short	Intelligent Bio-Responsive Fluorescent Au–shRNA Complexes for Regulated Autophagy and Effective Cancer Bioimaging and Therapeutics
title_full	Intelligent Bio-Responsive Fluorescent Au–shRNA Complexes for Regulated Autophagy and Effective Cancer Bioimaging and Therapeutics
title_fullStr	Intelligent Bio-Responsive Fluorescent Au–shRNA Complexes for Regulated Autophagy and Effective Cancer Bioimaging and Therapeutics
title_full_unstemmed	Intelligent Bio-Responsive Fluorescent Au–shRNA Complexes for Regulated Autophagy and Effective Cancer Bioimaging and Therapeutics
title_sort	intelligent bio-responsive fluorescent au–shrna complexes for regulated autophagy and effective cancer bioimaging and therapeutics
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f742f6f753174aa6b3f240643c5a7f7b
work_keys_str_mv	AT weijuancai intelligentbioresponsivefluorescentaushrnacomplexesforregulatedautophagyandeffectivecancerbioimagingandtherapeutics AT liangyin intelligentbioresponsivefluorescentaushrnacomplexesforregulatedautophagyandeffectivecancerbioimagingandtherapeutics AT huijiang intelligentbioresponsivefluorescentaushrnacomplexesforregulatedautophagyandeffectivecancerbioimagingandtherapeutics AT yossiweizmann intelligentbioresponsivefluorescentaushrnacomplexesforregulatedautophagyandeffectivecancerbioimagingandtherapeutics AT xuemeiwang intelligentbioresponsivefluorescentaushrnacomplexesforregulatedautophagyandeffectivecancerbioimagingandtherapeutics
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Intelligent Bio-Responsive Fluorescent Au–shRNA Complexes for Regulated Autophagy and Effective Cancer Bioimaging and Therapeutics

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