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      Switchable nanoparticle for programmed gene-chem delivery with enhanced neuronal recovery and CT imaging for neurodegenerative disease treatment

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          Abstract

          A designed polymer–gold nanoparticle programmatically co-delivers genes and chemical drugs with precise conversions between the delivery pathway and specific diseased cells.

          Abstract

          We present a facile approach of a switchable polymer–gold nanoparticle, which programmatically co-delivers genes and chemical drugs (gene-chem). Between the delivery pathway and specific diseased cells the nanoparticle is switchable and allows for enhanced computed tomography (CT) imaging and synergistic neuronal recovery. The delivery system with precise conversion will serve as a powerful gene-chem co-delivery platform to enable accurate brain disease therapy.

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          Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes.

          Lydia Alvarez-Erviti, Yiqi Seow, HaiFang Yin … (2011)
          To realize the therapeutic potential of RNA drugs, efficient, tissue-specific and nonimmunogenic delivery technologies must be developed. Here we show that exosomes-endogenous nano-vesicles that transport RNAs and proteins-can deliver short interfering (si)RNA to the brain in mice. To reduce immunogenicity, we used self-derived dendritic cells for exosome production. Targeting was achieved by engineering the dendritic cells to express Lamp2b, an exosomal membrane protein, fused to the neuron-specific RVG peptide. Purified exosomes were loaded with exogenous siRNA by electroporation. Intravenously injected RVG-targeted exosomes delivered GAPDH siRNA specifically to neurons, microglia, oligodendrocytes in the brain, resulting in a specific gene knockdown. Pre-exposure to RVG exosomes did not attenuate knockdown, and non-specific uptake in other tissues was not observed. The therapeutic potential of exosome-mediated siRNA delivery was demonstrated by the strong mRNA (60%) and protein (62%) knockdown of BACE1, a therapeutic target in Alzheimer's disease, in wild-type mice.
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            Pathogenesis of Parkinson's disease: dopamine, vesicles and alpha-synuclein.

            Julie Lotharius, Patrik Brundin (2002)
            Article 0 comments Cited 274 times – based on 0 reviews     Review now
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              Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats.

              Michelle Longmire, Peter L. Choyke, Hisataka Kobayashi (2008)
              Nanoparticles possess enormous potential as diagnostic imaging agents and hold promise for the development of multimodality agents with both imaging and therapeutic capabilities. Yet, some of the most promising nanoparticles demonstrate prolonged tissue retention and contain heavy metals. This presents serious concerns for toxicity. The creation of nanoparticles with optimal clearance characteristics will minimize toxicity risks by reducing the duration of exposure to these agents. Given that many nanoparticles possess easily modifiable surface and interior chemistry, if nanoparticle characteristics associated with optimal clearance from the body were well established, it would be feasible to design and create agents with more favorable clearance properties. This article presents a thorough discussion of the physiologic aspects of nanoparticle clearance, focusing on renal mechanisms, and provides an overview of current research investigating clearance of specific types of nanoparticles and nano-sized macromolecules, including dendrimers, quantum dots, liposomes and carbon, gold and silica-based nanoparticles.
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                Author and article information

                Contributors
                Journal
                Journal ID (publisher-id): MHAOAL
                Title: Materials Horizons
                Abbreviated Title: Mater. Horiz.
                Publisher: Royal Society of Chemistry (RSC)
                ISSN (Print): 2051-6347
                ISSN (Electronic): 2051-6355
                Publication date Created: October 14 2019
                Publication date (Electronic): 2019
                Volume: 6
                Issue: 9
                Pages: 1923-1929
                Affiliations
                [1 ]State Key Laboratory of Biochemical Engineering
                [2 ]Institute of Process Engineering
                [3 ]Chinese Academy of Sciences
                [4 ]Beijing 100190
                [5 ]P. R. China
                Article
                DOI: 10.1039/C9MH00482C
                SO-VID: e2f09e9f-f7e4-46c5-b313-f9fb3cf5da09
                Copyright © © 2019
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                http://rsc.li/journals-terms-of-use

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