A novel 4-arm DNA/RNA Nanoconstruct triggering Rapid Apoptosis of Triple Negative Breast Cancer Cells within 24 hours

Abstract Measuring at ~30 nm, a fully customizable holliday junction DNA nanoconstruct, was designed to simultaneously carry three unmodified SiRNA strands for apoptosis gene knockout in cancer cells without any assistance from commercial transfection kits. In brief, a holliday junction structure wa...

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Autores principales:	Joline Tung, Lih Shin Tew, Yuan-Man Hsu, Yit Lung Khung
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/88c8658fc8aa423486ffdf6b00b832d3
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spelling	oai:doaj.org-article:88c8658fc8aa423486ffdf6b00b832d32021-12-02T16:06:14ZA novel 4-arm DNA/RNA Nanoconstruct triggering Rapid Apoptosis of Triple Negative Breast Cancer Cells within 24 hours10.1038/s41598-017-00912-32045-2322https://doaj.org/article/88c8658fc8aa423486ffdf6b00b832d32017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00912-3https://doaj.org/toc/2045-2322Abstract Measuring at ~30 nm, a fully customizable holliday junction DNA nanoconstruct, was designed to simultaneously carry three unmodified SiRNA strands for apoptosis gene knockout in cancer cells without any assistance from commercial transfection kits. In brief, a holliday junction structure was intelligently designed to present one arm with a cell targeting aptamer (AS1411) while the remaining three arms to carry different SiRNA strands by means of DNA/RNA duplex for inducing apoptosis in cancer cells. By carrying the three SiRNA strands (AKT, MDM2 and Survivin) into triple negative breast MDA-MB-231 cancer cells, cell number had reduced by up to ~82% within 24 hours solely from one single administration of 32 picomoles. In the immunoblotting studies, up-elevation of phosphorylated p53 was observed for more than 8 hours while the three genes of interest were suppressed by nearly half by the 4-hour mark upon administration. Furthermore, we were able to demonstrate high cell selectivity of the nanoconstruct and did not exhibit usual morphological stress induced from liposomal-based transfection agents. To the best of the authors’ knowledge, this system represents the first of its kind in current literature utilizing a short and highly customizable holliday DNA junction to carry SiRNA for apoptosis studies.Joline TungLih Shin TewYuan-Man HsuYit Lung KhungNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joline Tung Lih Shin Tew Yuan-Man Hsu Yit Lung Khung A novel 4-arm DNA/RNA Nanoconstruct triggering Rapid Apoptosis of Triple Negative Breast Cancer Cells within 24 hours
description	Abstract Measuring at ~30 nm, a fully customizable holliday junction DNA nanoconstruct, was designed to simultaneously carry three unmodified SiRNA strands for apoptosis gene knockout in cancer cells without any assistance from commercial transfection kits. In brief, a holliday junction structure was intelligently designed to present one arm with a cell targeting aptamer (AS1411) while the remaining three arms to carry different SiRNA strands by means of DNA/RNA duplex for inducing apoptosis in cancer cells. By carrying the three SiRNA strands (AKT, MDM2 and Survivin) into triple negative breast MDA-MB-231 cancer cells, cell number had reduced by up to ~82% within 24 hours solely from one single administration of 32 picomoles. In the immunoblotting studies, up-elevation of phosphorylated p53 was observed for more than 8 hours while the three genes of interest were suppressed by nearly half by the 4-hour mark upon administration. Furthermore, we were able to demonstrate high cell selectivity of the nanoconstruct and did not exhibit usual morphological stress induced from liposomal-based transfection agents. To the best of the authors’ knowledge, this system represents the first of its kind in current literature utilizing a short and highly customizable holliday DNA junction to carry SiRNA for apoptosis studies.
format	article
author	Joline Tung Lih Shin Tew Yuan-Man Hsu Yit Lung Khung
author_facet	Joline Tung Lih Shin Tew Yuan-Man Hsu Yit Lung Khung
author_sort	Joline Tung
title	A novel 4-arm DNA/RNA Nanoconstruct triggering Rapid Apoptosis of Triple Negative Breast Cancer Cells within 24 hours
title_short	A novel 4-arm DNA/RNA Nanoconstruct triggering Rapid Apoptosis of Triple Negative Breast Cancer Cells within 24 hours
title_full	A novel 4-arm DNA/RNA Nanoconstruct triggering Rapid Apoptosis of Triple Negative Breast Cancer Cells within 24 hours
title_fullStr	A novel 4-arm DNA/RNA Nanoconstruct triggering Rapid Apoptosis of Triple Negative Breast Cancer Cells within 24 hours
title_full_unstemmed	A novel 4-arm DNA/RNA Nanoconstruct triggering Rapid Apoptosis of Triple Negative Breast Cancer Cells within 24 hours
title_sort	novel 4-arm dna/rna nanoconstruct triggering rapid apoptosis of triple negative breast cancer cells within 24 hours
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/88c8658fc8aa423486ffdf6b00b832d3
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A novel 4-arm DNA/RNA Nanoconstruct triggering Rapid Apoptosis of Triple Negative Breast Cancer Cells within 24 hours

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