Brain Targeted Gold Liposomes Improve RNAi Delivery for Glioblastoma

Nilmary Grafals-Ruiz,1,2 Christian I Rios-Vicil,2,3 Eunice L Lozada-Delgado,2,4 Blanca I Quiñones-Díaz,2,5 Ricardo A Noriega-Rivera,2,5 Gabriel Martínez-Zayas,2,6 Yasmarie Santana-Rivera,2 Ginette S Santiago-Sánchez,2,5 Fatma Valiyeva,2 Pablo E Vivas-Mej&a...

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Autores principales:	Grafals-Ruiz N, Rios-Vicil CI, Lozada-Delgado EL, Quiñones-Díaz BI, Noriega-Rivera RA, Martínez-Zayas G, Santana-Rivera Y, Santiago-Sánchez GS, Valiyeva F, Vivas-Mejía PE
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	glioblastoma (gbm) central nervous system (cns) micrornas rna interference spherical nucleic acids liposomes. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/9854bde5850244d3a2175c5e3970a90d
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spelling	oai:doaj.org-article:9854bde5850244d3a2175c5e3970a90d2021-12-02T15:19:54ZBrain Targeted Gold Liposomes Improve RNAi Delivery for Glioblastoma1178-2013https://doaj.org/article/9854bde5850244d3a2175c5e3970a90d2020-04-01T00:00:00Zhttps://www.dovepress.com/brain-targeted-gold-liposomes-improve-rnai-delivery-for-glioblastoma-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Nilmary Grafals-Ruiz,1,2 Christian I Rios-Vicil,2,3 Eunice L Lozada-Delgado,2,4 Blanca I Quiñones-Díaz,2,5 Ricardo A Noriega-Rivera,2,5 Gabriel Martínez-Zayas,2,6 Yasmarie Santana-Rivera,2 Ginette S Santiago-Sánchez,2,5 Fatma Valiyeva,2 Pablo E Vivas-Mejía2,5 1Department of Physiology, University of Puerto Rico, San Juan, Puerto Rico; 2Comprehensive Cancer Center, University of Puerto Rico, San Juan, Puerto Rico; 3Department of Neurosurgery, University of Puerto Rico, San Juan, Puerto Rico; 4Department of Biology, University of Puerto Rico, San Juan, Puerto Rico; 5Department of Biochemistry, University of Puerto Rico, San Juan, Puerto Rico; 6Department of Chemistry, University of Puerto Rico, San Juan, Puerto RicoCorrespondence: Pablo E Vivas-MejíaComprehensive Cancer Center, University of Puerto Rico, Medical Sciences Campus, San Juan 00935, Puerto RicoTel +1787 772 8300, ext 1114Fax +1787 758 2557Email pablo.vivas@upr.eduIntroduction: Glioblastoma (GBM) is the most common and lethal of the central nervous system (CNS) malignancies. The initiation, progression, and infiltration ability of GBMs are attributed in part to the dysregulation of microRNAs (miRNAs). Thus, targeting dysregulated miRNAs with RNA oligonucleotides (RNA interference, RNAi) has been proposed for GBM treatment. Despite promising results in the laboratory, RNA oligonucleotides have clinical limitations that include poor RNA stability and off-target effects. RNAi therapies against GBM confront an additional obstacle, as they need to cross the blood-brain barrier (BBB).Methods: Here, we developed gold-liposome nanoparticles conjugated with the brain targeting peptides apolipoprotein E (ApoE) and rabies virus glycoprotein (RVG). First, we functionalized gold nanoparticles with oligonucleotide miRNA inhibitors (OMIs), creating spherical nucleic acids (SNAs). Next, we encapsulated SNAs into ApoE, or RVG-conjugated liposomes, to obtain SNA-Liposome-ApoE and SNA-Liposome-RVG, respectively. We characterized each nanoparticle in terms of their size, charge, encapsulation efficiency, and delivery efficiency into U87 GBM cells in vitro. Then, they were administered intravenously (iv) in GBM syngeneic mice to evaluate their delivery efficiency to brain tumor tissue.Results: SNA-Liposomes of about 30– 50 nm in diameter internalized U87 GBM cells and inhibited the expression of miRNA-92b, an aberrantly overexpressed miRNA in GBM cell lines and GBM tumors. Conjugating SNA-Liposomes with ApoE or RVG peptides increased their systemic delivery to the brain tumors of GBM syngeneic mice. SNA-Liposome-ApoE demonstrated to accumulate at higher extension in brain tumor tissues, when compared with non-treated controls, SNA-Liposomes, or SNA-Liposome-RVG.Discussion: SNA-Liposome-ApoE has the potential to advance the translation of miRNA-based therapies for GBM as well as other CNS disorders.Keywords: glioblastoma, GBM, central nervous system, CNS, microRNAs, RNA interference, spherical nucleic acids, liposomesGrafals-Ruiz NRios-Vicil CILozada-Delgado ELQuiñones-Díaz BINoriega-Rivera RAMartínez-Zayas GSantana-Rivera YSantiago-Sánchez GSValiyeva FVivas-Mejía PEDove Medical Pressarticleglioblastoma (gbm)central nervous system (cns)micrornasrna interferencespherical nucleic acidsliposomes.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 2809-2828 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	glioblastoma (gbm) central nervous system (cns) micrornas rna interference spherical nucleic acids liposomes. Medicine (General) R5-920
spellingShingle	glioblastoma (gbm) central nervous system (cns) micrornas rna interference spherical nucleic acids liposomes. Medicine (General) R5-920 Grafals-Ruiz N Rios-Vicil CI Lozada-Delgado EL Quiñones-Díaz BI Noriega-Rivera RA Martínez-Zayas G Santana-Rivera Y Santiago-Sánchez GS Valiyeva F Vivas-Mejía PE Brain Targeted Gold Liposomes Improve RNAi Delivery for Glioblastoma
description	Nilmary Grafals-Ruiz,1,2 Christian I Rios-Vicil,2,3 Eunice L Lozada-Delgado,2,4 Blanca I Quiñones-Díaz,2,5 Ricardo A Noriega-Rivera,2,5 Gabriel Martínez-Zayas,2,6 Yasmarie Santana-Rivera,2 Ginette S Santiago-Sánchez,2,5 Fatma Valiyeva,2 Pablo E Vivas-Mejía2,5 1Department of Physiology, University of Puerto Rico, San Juan, Puerto Rico; 2Comprehensive Cancer Center, University of Puerto Rico, San Juan, Puerto Rico; 3Department of Neurosurgery, University of Puerto Rico, San Juan, Puerto Rico; 4Department of Biology, University of Puerto Rico, San Juan, Puerto Rico; 5Department of Biochemistry, University of Puerto Rico, San Juan, Puerto Rico; 6Department of Chemistry, University of Puerto Rico, San Juan, Puerto RicoCorrespondence: Pablo E Vivas-MejíaComprehensive Cancer Center, University of Puerto Rico, Medical Sciences Campus, San Juan 00935, Puerto RicoTel +1787 772 8300, ext 1114Fax +1787 758 2557Email pablo.vivas@upr.eduIntroduction: Glioblastoma (GBM) is the most common and lethal of the central nervous system (CNS) malignancies. The initiation, progression, and infiltration ability of GBMs are attributed in part to the dysregulation of microRNAs (miRNAs). Thus, targeting dysregulated miRNAs with RNA oligonucleotides (RNA interference, RNAi) has been proposed for GBM treatment. Despite promising results in the laboratory, RNA oligonucleotides have clinical limitations that include poor RNA stability and off-target effects. RNAi therapies against GBM confront an additional obstacle, as they need to cross the blood-brain barrier (BBB).Methods: Here, we developed gold-liposome nanoparticles conjugated with the brain targeting peptides apolipoprotein E (ApoE) and rabies virus glycoprotein (RVG). First, we functionalized gold nanoparticles with oligonucleotide miRNA inhibitors (OMIs), creating spherical nucleic acids (SNAs). Next, we encapsulated SNAs into ApoE, or RVG-conjugated liposomes, to obtain SNA-Liposome-ApoE and SNA-Liposome-RVG, respectively. We characterized each nanoparticle in terms of their size, charge, encapsulation efficiency, and delivery efficiency into U87 GBM cells in vitro. Then, they were administered intravenously (iv) in GBM syngeneic mice to evaluate their delivery efficiency to brain tumor tissue.Results: SNA-Liposomes of about 30– 50 nm in diameter internalized U87 GBM cells and inhibited the expression of miRNA-92b, an aberrantly overexpressed miRNA in GBM cell lines and GBM tumors. Conjugating SNA-Liposomes with ApoE or RVG peptides increased their systemic delivery to the brain tumors of GBM syngeneic mice. SNA-Liposome-ApoE demonstrated to accumulate at higher extension in brain tumor tissues, when compared with non-treated controls, SNA-Liposomes, or SNA-Liposome-RVG.Discussion: SNA-Liposome-ApoE has the potential to advance the translation of miRNA-based therapies for GBM as well as other CNS disorders.Keywords: glioblastoma, GBM, central nervous system, CNS, microRNAs, RNA interference, spherical nucleic acids, liposomes
format	article
author	Grafals-Ruiz N Rios-Vicil CI Lozada-Delgado EL Quiñones-Díaz BI Noriega-Rivera RA Martínez-Zayas G Santana-Rivera Y Santiago-Sánchez GS Valiyeva F Vivas-Mejía PE
author_facet	Grafals-Ruiz N Rios-Vicil CI Lozada-Delgado EL Quiñones-Díaz BI Noriega-Rivera RA Martínez-Zayas G Santana-Rivera Y Santiago-Sánchez GS Valiyeva F Vivas-Mejía PE
author_sort	Grafals-Ruiz N
title	Brain Targeted Gold Liposomes Improve RNAi Delivery for Glioblastoma
title_short	Brain Targeted Gold Liposomes Improve RNAi Delivery for Glioblastoma
title_full	Brain Targeted Gold Liposomes Improve RNAi Delivery for Glioblastoma
title_fullStr	Brain Targeted Gold Liposomes Improve RNAi Delivery for Glioblastoma
title_full_unstemmed	Brain Targeted Gold Liposomes Improve RNAi Delivery for Glioblastoma
title_sort	brain targeted gold liposomes improve rnai delivery for glioblastoma
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/9854bde5850244d3a2175c5e3970a90d
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Brain Targeted Gold Liposomes Improve RNAi Delivery for Glioblastoma

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