+1 Recommend
1 collections

      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

      105,621 Monthly downloads/views I 7.033 Impact Factor I 10.9 CiteScore I 1.22 Source Normalized Impact per Paper (SNIP) I 1.032 Scimago Journal & Country Rank (SJR)

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Brain Targeted Gold Liposomes Improve RNAi Delivery for Glioblastoma


      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.



          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).


          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.


          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.


          SNA-Liposome-ApoE has the potential to advance the translation of miRNA-based therapies for GBM as well as other CNS disorders.

          Most cited references82

          • Record: found
          • Abstract: not found
          • Article: not found

          Analysis of nanoparticle delivery to tumours

            • Record: found
            • Abstract: found
            • Article: not found

            DLS and zeta potential - What they are and what they are not?

            Adequate characterization of NPs (nanoparticles) is of paramount importance to develop well defined nanoformulations of therapeutic relevance. Determination of particle size and surface charge of NPs are indispensable for proper characterization of NPs. DLS (dynamic light scattering) and ZP (zeta potential) measurements have gained popularity as simple, easy and reproducible tools to ascertain particle size and surface charge. Unfortunately, on practical grounds plenty of challenges exist regarding these two techniques including inadequate understanding of the operating principles and dealing with critical issues like sample preparation and interpretation of the data. As both DLS and ZP have emerged from the realms of physical colloid chemistry - it is difficult for researchers engaged in nanomedicine research to master these two techniques. Additionally, there is little literature available in drug delivery research which offers a simple, concise account on these techniques. This review tries to address this issue while providing the fundamental principles of these techniques, summarizing the core mathematical principles and offering practical guidelines on tackling commonly encountered problems while running DLS and ZP measurements. Finally, the review tries to analyze the relevance of these two techniques from translatory perspective.
              • Record: found
              • Abstract: found
              • Article: not found

              Gold nanoparticles for biology and medicine.

              Gold colloids have fascinated scientists for over a century and are now heavily utilized in chemistry, biology, engineering, and medicine. Today these materials can be synthesized reproducibly, modified with seemingly limitless chemical functional groups, and, in certain cases, characterized with atomic-level precision. This Review highlights recent advances in the synthesis, bioconjugation, and cellular uses of gold nanoconjugates. There are now many examples of highly sensitive and selective assays based upon gold nanoconjugates. In recent years, focus has turned to therapeutic possibilities for such materials. Structures which behave as gene-regulating agents, drug carriers, imaging agents, and photoresponsive therapeutics have been developed and studied in the context of cells and many debilitating diseases. These structures are not simply chosen as alternatives to molecule-based systems, but rather for their new physical and chemical properties, which confer substantive advantages in cellular and medical applications.

                Author and article information

                Int J Nanomedicine
                Int J Nanomedicine
                International Journal of Nanomedicine
                23 April 2020
                : 15
                : 2809-2828
                [1 ]Department of Physiology, University of Puerto Rico , San Juan, Puerto Rico
                [2 ]Comprehensive Cancer Center, University of Puerto Rico , San Juan, Puerto Rico
                [3 ]Department of Neurosurgery, University of Puerto Rico , San Juan, Puerto Rico
                [4 ]Department of Biology, University of Puerto Rico , San Juan, Puerto Rico
                [5 ]Department of Biochemistry, University of Puerto Rico , San Juan, Puerto Rico
                [6 ]Department of Chemistry, University of Puerto Rico , San Juan, Puerto Rico
                Author notes
                Correspondence: Pablo E Vivas-Mejía Comprehensive Cancer Center, University of Puerto Rico, Medical Sciences Campus , San Juan00935, Puerto RicoTel +1787 772 8300, ext 1114Fax +1787 758 2557 Email pablo.vivas@upr.edu
                Author information
                © 2020 Grafals-Ruiz et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                : 04 December 2019
                : 27 March 2020
                Page count
                Figures: 8, Tables: 2, References: 106, Pages: 20
                Original Research

                Molecular medicine
                glioblastoma,gbm,central nervous system,cns,micrornas,rna interference,spherical nucleic acids,liposomes


                Comment on this article