Brain Targeted Gold Liposomes Improve RNAi Delivery for Glioblastoma
| Autor: | Nilmary, Grafals-Ruiz, Christian I, Rios-Vicil, Eunice L, Lozada-Delgado, Blanca I, Quiñones-Díaz, Ricardo A, Noriega-Rivera, Gabriel, Martínez-Zayas, Yasmarie, Santana-Rivera, Ginette S, Santiago-Sánchez, Fatma, Valiyeva, Pablo E, Vivas-Mejía |
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| Rok vydání: | 2019 |
| Předmět: |
Male
liposomes Oligonucleotides Metal Nanoparticles spherical nucleic acids GBM Apolipoproteins E RNA interference Viral Envelope Proteins Cell Line Tumor Nucleic Acids Animals Humans Original Research Brain Neoplasms Gene Transfer Techniques glioblastoma central nervous system Xenograft Model Antitumor Assays nervous system diseases microRNAs body regions Mice Inbred C57BL Blood-Brain Barrier Gold CNS |
| Zdroj: | International Journal of Nanomedicine |
| ISSN: | 1178-2013 |
| Popis: | Introduction 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. |
| Databáze: | OpenAIRE |
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