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      Hybrid magneto-plasmonic liposomes for multimodal image-guided and brain-targeted HIV treatment

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          Abstract

          Magneto-plasmonic liposomes were developed for image-guided drug delivery, and showed multimodal imaging, enhanced BBB transmigration, and reduction of viral replication.

          Abstract

          Image-guided drug delivery is an emerging strategy in the field of nanomedicine. The addition of image guidance to a traditional drug delivery system is expected to achieve highly efficient treatment by tracking the drug carriers in the body and monitoring their effective accumulation in the targeted tissues. In this study, we developed multifunctional magneto-plasmonic liposomes (MPLs), a hybrid system combining liposomes and magneto-plasmonic nanoparticles for a triple-modality image-guided drug delivery. Tenofovir disoproxil fumarate, an antiretroviral drug used to treat human immunodeficiency virus type 1 (HIV-1), was encapsulated into the MPLs to enable the treatment in the brain microenvironment, which is inaccessible to most of the drugs. We found strong negative and positive contrasts originating from the magnetic core of MPLs in magnetic resonance imaging (MRI) and magnetic particle imaging (MPI), respectively. The gold shell of MPLs showed bright positive contrast in X-ray computed tomography (CT). MPLs achieved enhanced transmigration across an in vitro blood–brain barrier (BBB) model by magnetic targeting. Moreover, MPLs provided desired therapeutic effects against HIV infected microglia cells.

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          Most cited references44

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          X-ray-computed tomography contrast agents.

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            Endocytic mechanisms for targeted drug delivery.

            Advances in the delivery of targeted drug systems have evolved to enable highly regulated site specific localization to subcellular organelles. Targeting therapeutics to individual intracellular compartments has resulted in benefits to therapies associated with these unique organelles. Endocytosis, a mechanism common to all cells in the body, internalizes macromolecules and retains them in transport vesicles which traffic along the endolysosomal scaffold. An array of vesicular internalization mechanisms exist, therefore understanding the key players specific to each pathway has allowed researchers to bioengineer macromolecular complexes for highly specialized delivery. Membrane specific receptors most frequently enter the cell through endocytosis following the binding of a high affinity ligand. High affinity ligands interact with membrane receptors, internalize in membrane bound vesicles, and traffic through cells in different manners to allow for accumulation in early endosomal fractions or lysosomally associated fractions. Although most drug delivery complexes aim to avoid lysosomal degradation, more recent studies have shown the clinical utility in directed protein delivery to this environment for the enzymatic release of therapeutics. Targeting nanomedicine complexes to the endolysosomal pathway has serious potential for improving drug delivery for the treatment of lysosomal storage diseases, cancer, and Alzheimer's disease. Although several issues remain for receptor specific targeting, current work is investigating a synthetic receptor approach for high affinity binding of targeted macromolecules.
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              Transport of drugs across the blood-brain barrier by nanoparticles.

              The central nervous system is well protected by the blood-brain barrier (BBB) which maintains its homeostasis. Due to this barrier many potential drugs for the treatment of diseases of the central nervous system (CNS) cannot reach the brain in sufficient concentrations. One possibility to deliver drugs to the CNS is the employment of polymeric nanoparticles. The ability of these carriers to overcome the BBB and to produce biologic effects on the CNS was shown in a number of studies. Over the past few years, progress in understanding of the mechanism of the nanoparticle uptake into the brain was made. This mechanism appears to be receptor-mediated endocytosis in brain capillary endothelial cells. Modification of the nanoparticle surface with covalently attached targeting ligands or by coating with certain surfactants enabling the adsorption of specific plasma proteins are necessary for this receptor-mediated uptake. The delivery of drugs, which usually are not able to cross the BBB, into the brain was confirmed by the biodistribution studies and pharmacological assays in rodents. Furthermore, the presence of nanoparticles in the brain parenchyma was visualized by electron microscopy. The intravenously administered biodegradable polymeric nanoparticles loaded with doxorubicin were successfully used for the treatment of experimental glioblastoma. These data, together with the possibility to employ nanoparticles for delivery of proteins and other macromolecules across the BBB, suggest that this technology holds great promise for non-invasive therapy of the CNS diseases. Copyright © 2011 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                NANOHL
                Nanoscale
                Nanoscale
                Royal Society of Chemistry (RSC)
                2040-3364
                2040-3372
                2018
                2018
                : 10
                : 1
                : 184-194
                Affiliations
                [1 ]Department of Immunology
                [2 ]Institute of NeuroImmune Pharmacology
                [3 ]Centre for Personalized Nanomedicine
                [4 ]Herbert Wertheim College of Medicine
                [5 ]Florida International University
                [6 ]Molecular Imaging Program at Stanford (MIPS)
                [7 ]The James H Clark Center
                [8 ]Stanford University
                [9 ]Stanford
                [10 ]USA
                [11 ]Department of Chemistry & Biochemistry
                [12 ]Southeast Environmental Research Center
                [13 ]Miami
                [14 ]Department of Psychiatry
                [15 ]McKnight Brain Institute
                [16 ]University of Florida College of Medicine
                [17 ]Gainesville
                [18 ]Department of Electrical and Computer Engineering
                [19 ]Yokohama National University
                [20 ]Yokohama 240-8501
                [21 ]Japan
                Article
                10.1039/C7NR07255D
                6450097
                29210401
                00fe3e8f-72ff-4363-916b-d254089cf3a0
                © 2018

                http://rsc.li/journals-terms-of-use

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