Arrowtail RNA for Ligand Display on Ginger Exosome-like Nanovesicles to Systemic Deliver siRNA for Cancer Suppression

Abstract Exosomes have shown increasing potential as delivery vesicles for therapy, but challenges like cost/yield, drug payload, and targeting specificity still exist. Plant derived exosome-like nanoparticles have been reported as a promising substitution and exhibit biocompatibility through oral,...

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Autores principales:	Zhefeng Li, Hongzhi Wang, Hongran Yin, Chad Bennett, Huang-ge Zhang, Peixuan Guo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Arrow Tail Survivin siRNA Equilibrium Density Gradient Ultracentrifugation Cushion Ultracentrifugation Vesicle Delivery Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cc70cbfff7874052ad1e5e21091fb87a
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spelling	oai:doaj.org-article:cc70cbfff7874052ad1e5e21091fb87a2021-12-02T15:07:56ZArrowtail RNA for Ligand Display on Ginger Exosome-like Nanovesicles to Systemic Deliver siRNA for Cancer Suppression10.1038/s41598-018-32953-72045-2322https://doaj.org/article/cc70cbfff7874052ad1e5e21091fb87a2018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-32953-7https://doaj.org/toc/2045-2322Abstract Exosomes have shown increasing potential as delivery vesicles for therapy, but challenges like cost/yield, drug payload, and targeting specificity still exist. Plant derived exosome-like nanoparticles have been reported as a promising substitution and exhibit biocompatibility through oral, intranasal administration; however, systemic delivery of siRNA by exosome-like nanoparticles directly isolated from plants has not been reported. Recently, we reported the control of RNA orientation to decorate human derived exosome with cell targeting ligands for specific delivery of siRNA to tumors. Here, we expand to the application of arrowtail RNA nanoparticles for displaying ligands on ginger derived exosome-like nanovesicles (GDENs) for siRNA delivery and tumor inhibition through IV administration. Cushion ultracentrifugation coupled with equilibrium density gradient ultracentrifugation were used for purifying GDENs that displayed size, density, and morphology similar to human derived exosomes. Folic acid (FA), as a ligand, was displayed on the surface of GDENs for targeted delivery of survivin siRNA to KB cancer models. In vitro gene knockdown efficacy by FA-3WJ/GDENs/siRNA complex was comparable to transfection. We observed inhibition of tumor growth on a xenograft model by intravenous administration, which reveals the potential of GDENs as an economic delivery system for siRNA.Zhefeng LiHongzhi WangHongran YinChad BennettHuang-ge ZhangPeixuan GuoNature PortfolioarticleArrow TailSurvivin siRNAEquilibrium Density Gradient UltracentrifugationCushion UltracentrifugationVesicle DeliveryMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arrow Tail Survivin siRNA Equilibrium Density Gradient Ultracentrifugation Cushion Ultracentrifugation Vesicle Delivery Medicine R Science Q
spellingShingle	Arrow Tail Survivin siRNA Equilibrium Density Gradient Ultracentrifugation Cushion Ultracentrifugation Vesicle Delivery Medicine R Science Q Zhefeng Li Hongzhi Wang Hongran Yin Chad Bennett Huang-ge Zhang Peixuan Guo Arrowtail RNA for Ligand Display on Ginger Exosome-like Nanovesicles to Systemic Deliver siRNA for Cancer Suppression
description	Abstract Exosomes have shown increasing potential as delivery vesicles for therapy, but challenges like cost/yield, drug payload, and targeting specificity still exist. Plant derived exosome-like nanoparticles have been reported as a promising substitution and exhibit biocompatibility through oral, intranasal administration; however, systemic delivery of siRNA by exosome-like nanoparticles directly isolated from plants has not been reported. Recently, we reported the control of RNA orientation to decorate human derived exosome with cell targeting ligands for specific delivery of siRNA to tumors. Here, we expand to the application of arrowtail RNA nanoparticles for displaying ligands on ginger derived exosome-like nanovesicles (GDENs) for siRNA delivery and tumor inhibition through IV administration. Cushion ultracentrifugation coupled with equilibrium density gradient ultracentrifugation were used for purifying GDENs that displayed size, density, and morphology similar to human derived exosomes. Folic acid (FA), as a ligand, was displayed on the surface of GDENs for targeted delivery of survivin siRNA to KB cancer models. In vitro gene knockdown efficacy by FA-3WJ/GDENs/siRNA complex was comparable to transfection. We observed inhibition of tumor growth on a xenograft model by intravenous administration, which reveals the potential of GDENs as an economic delivery system for siRNA.
format	article
author	Zhefeng Li Hongzhi Wang Hongran Yin Chad Bennett Huang-ge Zhang Peixuan Guo
author_facet	Zhefeng Li Hongzhi Wang Hongran Yin Chad Bennett Huang-ge Zhang Peixuan Guo
author_sort	Zhefeng Li
title	Arrowtail RNA for Ligand Display on Ginger Exosome-like Nanovesicles to Systemic Deliver siRNA for Cancer Suppression
title_short	Arrowtail RNA for Ligand Display on Ginger Exosome-like Nanovesicles to Systemic Deliver siRNA for Cancer Suppression
title_full	Arrowtail RNA for Ligand Display on Ginger Exosome-like Nanovesicles to Systemic Deliver siRNA for Cancer Suppression
title_fullStr	Arrowtail RNA for Ligand Display on Ginger Exosome-like Nanovesicles to Systemic Deliver siRNA for Cancer Suppression
title_full_unstemmed	Arrowtail RNA for Ligand Display on Ginger Exosome-like Nanovesicles to Systemic Deliver siRNA for Cancer Suppression
title_sort	arrowtail rna for ligand display on ginger exosome-like nanovesicles to systemic deliver sirna for cancer suppression
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/cc70cbfff7874052ad1e5e21091fb87a
work_keys_str_mv	AT zhefengli arrowtailrnaforliganddisplayongingerexosomelikenanovesiclestosystemicdeliversirnaforcancersuppression AT hongzhiwang arrowtailrnaforliganddisplayongingerexosomelikenanovesiclestosystemicdeliversirnaforcancersuppression AT hongranyin arrowtailrnaforliganddisplayongingerexosomelikenanovesiclestosystemicdeliversirnaforcancersuppression AT chadbennett arrowtailrnaforliganddisplayongingerexosomelikenanovesiclestosystemicdeliversirnaforcancersuppression AT huanggezhang arrowtailrnaforliganddisplayongingerexosomelikenanovesiclestosystemicdeliversirnaforcancersuppression AT peixuanguo arrowtailrnaforliganddisplayongingerexosomelikenanovesiclestosystemicdeliversirnaforcancersuppression
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Arrowtail RNA for Ligand Display on Ginger Exosome-like Nanovesicles to Systemic Deliver siRNA for Cancer Suppression

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