Design of cyclic RGD-conjugated Aib-containing amphipathic helical peptides for targeted delivery of small interfering RNA

2016 ◽  
Vol 24 (18) ◽  
pp. 4478-4485 ◽  
Author(s):  
Shun-ichi Wada ◽  
Masashi Iwata ◽  
Yuka Ozaki ◽  
Takashi Ozaki ◽  
Junsuke Hayashi ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Small Interfering Rna ◽  
Helical Peptides ◽  
Interfering Rna

Targeted delivery of small interfering RNA to colon cancer cells using chitosan and PEGylated chitosan nanoparticles

2016 ◽  
Vol 147 ◽  
pp. 323-332 ◽  
Author(s):  
Walter E. Rudzinski ◽  
Adriana Palacios ◽  
Abuzar Ahmed ◽  
Michelle A. Lane ◽  
Tejraj M. Aminabhavi
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Small Interfering Rna ◽  
Chitosan Nanoparticles ◽  
Colon Cancer Cells ◽  
Interfering Rna

scholarly journals Targeted Delivery of Small Interfering RNA Using Reconstituted High-Density Lipoprotein Nanoparticles

Neoplasia ◽  
2011 ◽  
Vol 13 (4) ◽  
pp. 309-IN8 ◽  
Author(s):  
Mian M.K. Shahzad ◽  
Lingegowda S. Mangala ◽  
Hee Dong Han ◽  
Chunhua Lu ◽  
Justin Bottsford-Miller ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Targeted Delivery ◽  
Small Interfering Rna ◽  
Density Lipoprotein ◽  
High Density ◽  
Interfering Rna

scholarly journals Multivalent Cyclic RGD Conjugates for Targeted Delivery of Small Interfering RNA

2011 ◽  
Vol 22 (8) ◽  
pp. 1673-1681 ◽  
Author(s):  
Md. Rowshon Alam ◽  
Xin Ming ◽  
Michael Fisher ◽  
Jeremy G. Lackey ◽  
Kallanthottathil G. Rajeev ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Small Interfering Rna ◽  
Interfering Rna

scholarly journals Targeted Delivery of Small Interfering RNA to Human Dendritic Cells To Suppress Dengue Virus Infection and Associated Proinflammatory Cytokine Production

2009 ◽  
Vol 84 (5) ◽  
pp. 2490-2501 ◽  
Author(s):  
Sandesh Subramanya ◽  
Sang-Soo Kim ◽  
Sojan Abraham ◽  
Jiahong Yao ◽  
Mukesh Kumar ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dengue Virus ◽  
Virus Replication ◽  
Targeted Delivery ◽  
Small Interfering Rna ◽  
Envelope Gene ◽  
Hematopoietic Stem ◽  
Tnf Α ◽  
Interfering Rna

ABSTRACT Dengue is a common arthropod-borne flaviviral infection in the tropics, for which there is no vaccine or specific antiviral drug. The infection is often associated with serious complications such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), in which both viral and host factors have been implicated. RNA interference (RNAi) is a potent antiviral strategy and a potential therapeutic option for dengue if a feasible strategy can be developed for delivery of small interfering RNA (siRNA) to dendritic cells (DCs) and macrophages, the major in vivo targets of the virus and also the source of proinflammatory cytokines. Here we show that a dendritic cell-targeting 12-mer peptide (DC3) fused to nona-d-arginine (9dR) residues (DC3-9dR) delivers siRNA and knocks down endogenous gene expression in heterogenous DC subsets, (monocyte-derived DCs [MDDCs], CD34+ hematopoietic stem cell [HSC])-derived Langerhans DCs, and peripheral blood DCs). Moreover, DC3-9dR-mediated delivery of siRNA targeting a highly conserved sequence in the dengue virus envelope gene (siFvED) effectively suppressed dengue virus replication in MDDCs and macrophages. In addition, DC-specific delivery of siRNA targeting the acute-phase cytokine tumor necrosis factor alpha (TNF-α), which plays a major role in dengue pathogenesis, either alone or in combination with an antiviral siRNA, significantly reduced virus-induced production of the cytokine in MDDCs. Finally to validate the strategy in vivo, we tested the ability of the peptide to target human DCs in the NOD/SCID/IL-2Rγ−/− mouse model engrafted with human CD34+ hematopoietic stem cells (HuHSC mice). Treatment of mice by intravenous (i.v.) injection of DC3-9dR-complexed siRNA targeting TNF-α effectively suppressed poly(I:C)-induced TNF-α production by DCs. Thus, DC3-9dR can deliver siRNA to DCs both in vitro and in vivo, and this delivery approach holds promise as a therapeutic strategy to simultaneously suppress virus replication and curb virus-induced detrimental host immune responses in dengue infection.

Advances in targeted delivery of small interfering RNA using simple bioconjugates

2014 ◽  
Vol 11 (5) ◽  
pp. 791-822 ◽  
Author(s):  
Christoffer Nielsen ◽  
Jørgen Kjems ◽  
Kristine Rothaus Sørensen ◽  
Lars Henning Engelholm ◽  
Niels Behrendt
Keyword(s):  
Targeted Delivery ◽  
Small Interfering Rna ◽  
Interfering Rna

scholarly journals Cytotoxicity assessment, inflammatory properties, and cellular uptake of Neutraplex lipid-based nanoparticles in THP-1 monocyte-derived macrophages

2017 ◽  
Vol 4 ◽  
pp. 184954351774625 ◽  
Author(s):  
Eric Berger ◽  
Dalibor Breznan ◽  
Sandra Stals ◽  
Viraj J Jasinghe ◽  
David Gonçalves ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Small Interfering Rna ◽  
Human Monocyte ◽  
Antiretroviral Drugs ◽  
Small Interfering Rnas ◽  
Lactate Dehydrogenase Release ◽  
Drug Concentrations ◽  
Interfering Rna ◽  
Hiv 1

Current antiretroviral drugs used to prevent or treat human immunodeficiency virus type 1 (HIV-1) infection are not able to eliminate the virus within tissues or cells where HIV establishes reservoirs. Hence, there is an urgent need to develop targeted delivery systems to enhance drug concentrations in these viral sanctuary sites. Macrophages are key players in HIV infection and contribute significantly to the cellular reservoirs of HIV because the virus can survive for prolonged periods in these cells. In the present work, we investigated the potential of the lipid-based Neutraplex nanosystem to deliver anti-HIV therapeutics in human macrophages using the human monocyte/macrophage cell line THP-1. Neutraplex nanoparticles as well as cationic and anionic Neutraplex nanolipoplexes (Neutraplex/small interfering RNA) were prepared and characterized by dynamic light scattering. Neutraplex nanoparticles showed low cytotoxicity in CellTiter-Blue reduction and lactate dehydrogenase release assays and were not found to have pro-inflammatory effects. In addition, confocal studies showed that the Neutraplex nanoparticles and nanolipoplexes are rapidly internalized into THP-1 macrophages and that they can escape the late endosome/lysosome compartment allowing the delivery of small interfering RNAs in the cytoplasm. Furthermore, HIV replication was inhibited in the in vitro TZM-bl infectivity assay when small interfering RNAs targeting CXCR4 co-receptor was delivered by Neutraplex nanoparticles compared to a random small interfering RNA sequence. This study demonstrates that the Neutraplex nanosystem has potential for further development as a delivery strategy to efficiently and safely enhance the transport of therapeutic molecules into human monocyte-derived macrophages in the aim of targeting HIV-1 in this cellular reservoir.

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