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Total 1410 results found since Jan 2013.

Positron Emission Tomography Studies of the Biodistribution, Translocation, and Fate of Poly Allyl Amine ‐Based Carriers for Sirna Delivery by Systemic and Intratumoral Administration.
Positron emission tomography is used to study the fate of polyplexes formed by siRNA and modified polyamines. Polyplexes are prepared with either radiolabeled siRNA or radiolabeled polyamines. By comparing biodistribution patterns of labeled siRNA and labeled polyamines conclusions are driven on the stability of the polyplexes in vivo. AbstractPolyamine-based vectors offer many advantages for gene therapy, but they are hampered by a limited knowledge on their biological fate and efficacy for nucleic acid delivery. The18F radiolabeled siRNA is complexed with poly(allyl amine) hydrochloride (PAH), PEGylated PAH (PAHPEG), or ...
Source: Small - August 4, 2023 Category: Nanotechnology Authors: Cristina Simo, Cristian Salvador, Patrizia Andreozzi, Vanessa Gomez ‐Vallejo, Gabriela Romero, Damien Dupin, Jordi Llop, Sergio E. Moya Tags: Research Article Source Type: research

Attachment of Cell-Binding Ligands to Arginine-Rich Cell-Penetrating Peptides Enables Cytosolic Translocation of Complexed siRNA.
Abstract Cell-penetrating peptides (CPPs), such as nona-arginine (9R), poorly translocate siRNA into cells. Our studies demonstrate that attaching 9R to ligands that bind cell surface receptors quantitatively increases siRNA uptake and importantly, allows functional delivery of complexed siRNA. The mechanism involved accumulation of ligand-9R:siRNA microparticles on the cell membrane, which induced transient membrane inversion at the site of ligand-9R binding and rapid siRNA translocation into the cytoplasm. siRNA release also occurred late after endocytosis when the ligand was attached to the L isoform of 9R, but...
Source: Chemistry and Biology - December 23, 2014 Category: Chemistry Authors: Zeller S, Choi CS, Uchil PD, Ban H, Siefert A, Fahmy TM, Mothes W, Lee S, Kumar P Tags: Chem Biol Source Type: research

Inhibition of HIV replication through siRNA carried by CXCR4-targeted chimeric nanobody.
Abstract Small interfering RNA (siRNA) application in therapy still faces a major challenge with the lack of an efficient and specific delivery system. Current vehicles are often responsible for poor efficacy, safety concerns, and burden costs of siRNA-based therapeutics. Here, we describe a novel strategy for targeted delivery of siRNA molecules to inhibit human immunodeficiency virus (HIV) infection. Specific membrane translocation of siRNA inhibitor was addressed by an engineered nanobody targeting the HIV co-receptor CXCR4 (NbCXCR4) in fusion with a single-chain variable fragment (4M5.3) that carried the FITC-...
Source: Cellular and Molecular Life Sciences : CMLS - October 21, 2019 Category: Cytology Authors: Cunha-Santos C, Perdigao PRL, Martin F, Oliveira JG, Cardoso M, Manuel A, Taveira N, Goncalves J Tags: Cell Mol Life Sci Source Type: research

Trends in the Binding of Cell Penetrating Peptides to siRNA: A Molecular Docking Study.
Authors: Rathnayake PV, Gunathunge BG, Wimalasiri PN, Karunaratne DN, Ranatunga RJ Abstract The use of gene therapeutics, including short interfering RNA (siRNA), is limited by the lack of efficient delivery systems. An appealing approach to deliver gene therapeutics involves noncovalent complexation with cell penetrating peptides (CPPs) which are able to penetrate the cell membranes of mammals. Although a number of CPPs have been discovered, our understanding of their complexation and translocation of siRNA is as yet insufficient. Here, we report on computational studies comparing the binding affinities of CPPs wi...
Source: Journal of Biophysics - March 24, 2017 Category: Physics Tags: J Biophys Source Type: research

In vitro siRNA delivery via diethylenetriamine- and tetraethylenepentamine-modified carboxyl group-terminated Poly(amido)amine generation 4.5 dendrimers
Publication date: January 2020Source: Materials Science and Engineering: C, Volume 106Author(s): Endiries Yibru Hanurry, Wei-Hsin Hsu, Haile Fentahun Darge, Yihenew Simegniew Birhan, Tefera Worku Mekonnen, Abegaz Tizazu Andrgie, Hsiao-Ying Chou, Chih-Chia Cheng, Juin-Yih Lai, Hsieh-Chih TsaiAbstractThe recent discovery of small interfering RNAs (siRNAs) has opened new avenues for designing personalized treatment options for various diseases. However, the therapeutic application of siRNAs has been confronted with many challenges because of short half-life in circulation, poor membrane penetration, difficulty in escaping fro...
Source: Materials Science and Engineering: C - October 18, 2019 Category: Materials Science Source Type: research

Abstract 718: Systemic delivery of therapeutic siRNA by multifunctional mesoporous silica-based nanocarrier inhibits lung cancer growth and metastasis
In this study, we developed a novel siRNA delivery vector based on our magnetic mesoporous silica nanoparticles (M-MSNs) platform. This nanocarrier was constructed by loading siRNAs into the mesopores of M-MSNs, followed by polyethylenimine (PEI) capping, PEGylation and fusogenic peptide KALA modification. The resultant functionalized delivery system exhibited prolonged half-life in bloodstream, enhanced cell membrane translocation and endosomal escapablity, and favorable tissue biocompatibility and biosafety. Systemic application of vascular endothelial growth factor (VEGF) siRNA via this nanocarrier resulted in remarkabl...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Chen, Y., Gu, H., Xia, W. Tags: Experimental and Molecular Therapeutics Source Type: research

Multifunctional magnetite nanoparticles to enable delivery of siRNA for the potential treatment of Alzheimer's.
This study aims to explore the ability of a multifunctional conjugate based on magnetite nanoparticles for the cellular delivery of siRNA against the expression of the BACE1 gene. We immobilized the siRNA strand on PEGylated magnetite nanoparticles and investigated the effects on biocompatibility and efficacy of the conjugation. Similarly, we co-immobilized the translocating protein OmpA on PEGylated nanoparticles to enhance cellular uptake and endosomal escape. BACE1 suppression was statistically significant in HFF-1 cells, without any presence of a cytotoxic effect. The delivery of the nanoconjugate was achieved through ...
Source: Drug Delivery - June 11, 2020 Category: Drugs & Pharmacology Tags: Drug Deliv Source Type: research

Translocation and encapsulation of siRNA inside carbon nanotubes
We report spontaneous translocation of small interfering RNA (siRNA) inside carbon nanotubes (CNTs) of various diameters and chirality using all atom molecular dynamics simulations with explicit solvent. We use umbrella sampling method to calculate the free energy landscape of the siRNA entry and tr ... [J. Chem. Phys. 138, 034901 (2013)] published Tue Jan 15, 2013.
Source: Journal of Chemical Physics - January 16, 2013 Category: Physics Source Type: research

SiRNA Nanotherapeutics - The Panacea of Diseases?
This article will present the major impediments that encumber successful translation of siRNA concept into reality and the ongoing research endeavours to get through those stumbling blocks along with their inadequacies. PMID: 25612905 [PubMed - as supplied by publisher]
Source: Current Gene Therapy - January 22, 2015 Category: Genetics & Stem Cells Authors: Badrealam KF, Zubair S, Owais M Tags: Curr Gene Ther Source Type: research

Tips and Tools to Understand Direct Membrane Translocation of siRNA-Loaded WRAP-Based Nanoparticles
Methods Mol Biol. 2022;2383:475-490. doi: 10.1007/978-1-0716-1752-6_30.ABSTRACTCell-penetrating peptide (CPP)-based approaches are excellent method for delivering cell-impermeable compounds/therapeutics such as proteins, antibodies, antisense oligonucleotides, siRNAs, plasmids, and drugs, as covalently or noncovalently conjugated cargo into cells. Nowadays, it is generally accepted that cellular internalization of these CPP-cargoes or CPP-nanoparticles occur via endocytosis-dependent mechanisms or by direct cell translocation.Here, we describe a subset of biophysical and biological methods which can be used to dissect the ...
Source: Mol Biol Cell - November 12, 2021 Category: Molecular Biology Authors: S ébastien Deshayes Karidia Konate Eric Viv ès Prisca Boisgu érin Source Type: research

GSE39963 Distinct signal transduction pathways downstream of the (P)RR revealed by microarray and ChIP-chip analyses Expt: siRNA
Contributors : Heiko Funke-Kaiser ; Daniela ZaadeSeries Type : Expression profiling by arrayOrganism : Homo sapiensWithin the overall project, we performed a set of microarray and chromatin-immunoprecipitation (ChIP)-chip experiments using siRNA against the (pro)renin receptor ((P)RR), stable overexpression of PLZF, the PLZF translocation inhibitor genistein and the specific V-ATPase inhibitor bafilomycin to dissect transcriptional pathways downstream of the (P)RR.
Source: GEO: Gene Expression Omnibus - August 7, 2015 Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research

Regulation on Toll-like Receptor 4 and Cell Barrier Function by Rab26 siRNA-loaded DNA Nanovector in Pulmonary Microvascular Endothelial Cells
In this study, we thoroughly investigated the role and novel mechanism of Rab26 in permeability and apoptosis of HPMVECs using a self-assembled Rab26 siRNA loaded DNA Y-motif nanoparticle (siRab26-DYM) and Rab26 adenovirus. We found that siRab26-DYM could be efficiently transfected into HPMVECs in a time- and dose-dependent manner. Importantly, the siRab26-DYM nanovector markedly aggravated the LPS-induced apoptosis and hyper-permeability of HPMVECs by promoting the nuclear translocation of Foxo1, and subsequent activation of Toll-like receptor 4 (TLR4) signal pathway. Overexpression of Rab26 by Rab26 adenoviruses partiall...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Hongli Li, Binfeng He, Xueping Liu, Jingtong Li, Qian Liu, Weijie Dong, Zhi Xu, Guisheng Qian, Hua Zuo, Changhua Hu, Hang Qian, Chengde Mao, Guansong Wang Tags: Research Paper Source Type: research

Lipid-based DNA/siRNA transfection agents disrupt neuronal bioenergetics and mitophagy.
Abstract A multitude of natural and artificial compounds have been recognized to modulate autophagy, providing direct or, through associated pathways, indirect entry points to activation and inhibition. While these pharmacological tools are extremely useful in the study of autophagy, their abundance also suggests the potential presence of unidentified autophagic modulators that may interfere with experimental designs if applied unknowingly. Here, we report unanticipated effects on autophagy and bioenergetics in neuronal progenitor cells (NPC) incubated with widely used lipid-based-transfection reagent lipofectamin...
Source: The Biochemical Journal - October 12, 2017 Category: Biochemistry Authors: Napoli E, Liu S, Marsilio I, Zarbalis K, Giulivi C Tags: Biochem J Source Type: research

Self-amplified ROS production from fatty acid oxidation enhanced tumor immunotherapy by atorvastatin/PD-L1 siRNA lipopeptide nanoplexes
Biomaterials. 2022 Nov 3;291:121902. doi: 10.1016/j.biomaterials.2022.121902. Online ahead of print.ABSTRACTDespite the important role of reactive oxygen species (ROS) in battling cancer, ROS production with current approaches has been severely limited by the deficiency of oxy-substrates in tumor microenvironment. Herein, an atorvastatin (Ato)-catalytic self-amplified approach was utilized for sustainable ROS production and enhancing anti-tumor efficacy of PD-L1 silencing. A C18-pArg8-ss-pHis10 lipopeptide based self-assembled nanoplexes was developed to co-encapsulate AMP-activated protein kinase (AMPK) activator of Ato a...
Source: Biomaterials - November 13, 2022 Category: Materials Science Authors: Yan Gao Zilin Song Li Jia Yi Tang Chengcheng Wang Xiuli Zhao Haiyang Hu Dawei Chen Mingxi Qiao Source Type: research