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Total 41092 results found since Jan 2013.

In vivo disassembly of IV administered siRNA matrix nanoparticles at the renal filtration barrier.
In this report, the biodistribution in mice of siRNA loaded dextran nanogels was investigated in detail. Both single photon emission computed tomography (SPECT) imaging and fluorescence single particle tracking (fSPT) indicate that the particles are rapidly cleared from the circulation. PEGylation of the nanogels was not able to increase the half-life in the bloodstream. Carrier disassembly in the systemic circulation and phagocytic clearance are known to facilitate the elimination of siRNA nanoparticles. Additionally, it is demonstrated for dextran nanogels that also the kidneys play an important role in their elimination...
Source: Biomaterials - December 19, 2012 Category: Materials Science Authors: Naeye B, Deschout H, Caveliers V, Descamps B, Braeckmans K, Vanhove C, Demeester J, Lahoutte T, De Smedt SC, Raemdonck K Tags: Biomaterials Source Type: research

Cellular internalization and gene silencing of siRNA polyplexes by cytocleavable cationic polyrotaxanes with tailored rigid backbones.
Abstract To achieve successful delivery of siRNA therapeutics, cytocleavable cationic polyrotaxanes (PRXs) composed of N,N-dimethylaminoethyl (DMAE) group-modified α-cyclodextrins (CDs) that were threaded onto a poly(ethylene glycol) (PEG) axis and capped with a bulky stopper using cytocleavable disulfide linkages (DMAE-PRX) were utilized as an siRNA carrier. DMAE-PRXs with various numbers of threading CDs and modified DMAE groups were synthesized, and the physicochemical properties, cellular internalization, and gene silencing activity of DMAE-PRX/siRNA were investigated to elucidate the relationship between its...
Source: Biomaterials - January 30, 2013 Category: Materials Science Authors: Tamura A, Yui N Tags: Biomaterials Source Type: research

Influence of cationic lipid composition on uptake and intracellular processing of lipid nanoparticle formulations of siRNA
This study reports on the in vivo gene silencing potency of lipid nanoparticle-siRNA systems containing ionizable cationic lipids. It is concluded that the superior potency of DLinKC2-DMA compared with DLinKDMA or DLinDMA can be attributed to their higher uptake thus improved ability to stimulate siRNA release from endosome.Graphical Abstract: Uptake of lipid nanoparticle (LNP) formulations of siRNA into cells. (1) LNP-siRNA associates with cell membrane followed by (2) internalization. As the pH decreases in the endosomes the ionizable cationic lipids associate with endogenous anionic lipids to destabilize the endosomal m...
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - June 14, 2012 Category: Nanotechnology Authors: Paulo J.C. Lin, Yuen Yi C. Tam, Ismail Hafez, Ammen Sandhu, Sam Chen, Marco A. Ciufolini, Ivan R. Nabi, Pieter R. Cullis Tags: QV Pharmacology, Pharmaceutical Technology, Gene Transfection, Lipid NPs Source Type: research

Actively-targeted polyion complex micelles stabilized by cholesterol and disulfide cross-linking for systemic delivery of siRNA to solid tumors.
Abstract For small interfering RNA (siRNA)-based cancer therapies, we report an actively-targeted and stabilized polyion complex micelle designed to improve tumor accumulation and cancer cell uptake of siRNA following systemic administration. Improvement in micelle stability was achieved using two stabilization mechanisms; covalent disulfide cross-linking and non-covalent hydrophobic interactions. The polymer component was designed to provide disulfide cross-linking and cancer cell-targeting cyclic RGD peptide ligands, while cholesterol-modified siRNA (Chol-siRNA) provided additional hydrophobic stabilization to t...
Source: Biomaterials - June 12, 2014 Category: Materials Science Authors: Oe Y, Christie RJ, Naito M, Low SA, Fukushima S, Toh K, Miura Y, Matsumoto Y, Nishiyama N, Miyata K, Kataoka K Tags: Biomaterials Source Type: research

Novel siRNA Delivery System Using a Ternary Polymer Complex with Strong Silencing Effect and No Cytotoxicity.
Abstract We developed a novel small interfering RNA (siRNA) delivery system using a ternary complex with polyethyleneimine (PEI) and γ-polyglutamic acid (γ-PGA), which showed silencing effect and no cytotoxicity. The binary complexes of siRNA with PEI were approximately 73-102 nm in particle size and 45-52 mV in ζ-potential. The silencing effect of siRNA/PEI complexes increased with an increase of PEI, and siRNA/PEI complexes with a charge ratio greater than 16 showed significant luciferase knockdown in a mouse colon carcinoma cell line regularly expressing luciferase (Colon26/Luc cells). However, strong cy...
Source: Biological and Pharmaceutical Bulletin - August 9, 2014 Category: Drugs & Pharmacology Authors: Kodama Y, Shiokawa Y, Nakamura T, Kurosaki T, Aki K, Nakagawa H, Muro T, Kitahara T, Higuchi N, Sasaki H Tags: Biol Pharm Bull Source Type: research

Efficient in vitro gene therapy with PEG siRNA lipid nanocapsules for passive targeting strategy in melanoma.
The objective of this work consists in formulating and optimizing the encapsulation of siRNA into lipid nanocapsules (LNCs) for efficient gene therapy on melanoma cells. SiRNA LNCs were prepared from DOTAP/DOPE lipoplexes, and the siRNA dose and lipid/siRNA charge ratio were assayed to improve the stability and encapsulation yield. Cryo-TEM imaging of the siRNA lipoplexes and LNC morphology revealed a specific organization of the siRNA DOTAP/DOPE lipoplexes as well as specific lipid microstructures. No cytotoxicity of the siRNA LNCs against the melanoma SK-Mel28 cell line was observed at concentrations of up to 500 ng/mL s...
Source: Biotechnology Journal - September 26, 2014 Category: Biotechnology Authors: Resnier P, LeQuinio P, Lautram N, André E, Gaillard C, Bastiat G, Benoit JP, Passirani C Tags: Biotechnol J Source Type: research

Combination of BCL11A siRNA with vincristine increases the apoptosis of SUDHL6 cells
Conclusions The combination of BCL11A siRNA and VCR increases apoptosis in SUDHL6 cells. Our study implies that BCL11A siRNA in combination with VCR may be a useful approach for improving effective treatment for B cell lymphoma.
Source: European Journal of Medical Research - June 24, 2014 Category: Research Source Type: research

TPX2 siRNA regulates growth and invasion of esophageal cancer cells
Conclusion siRNA could effectively inhibit the invasion and metastasis of EC9706 cells, promote the apoptosis of tumor cells and may become a new approach for treatment of esophageal carcinoma.
Source: Biomedicine and Pharmacotherapy - November 1, 2014 Category: Drugs & Pharmacology Source Type: research

In vivo siRNA delivery system for targeting to the liver by poly-l-glutamic acid-coated lipoplex
In this study, we developed anionic polymer-coated liposome/siRNA complexes (lipoplexes) with chondroitin sulfate C (CS), poly-l-glutamic acid (PGA) and poly-aspartic acid (PAA) for siRNA delivery by intravenous injection, and evaluated the biodistribution and gene silencing effect in mice. The sizes of CS-, PGA- and PAA-coated lipoplexes were about 200 nm and their ζ-potentials were negative. CS-, PGA- and PAA-coated lipoplexes did not induce agglutination after mixing with erythrocytes. In terms of biodistribution, siRNAs after intravenous administration of cationic lipoplexes were largely observed in the lungs, but t...
Source: Results in Pharma Sciences - October 12, 2014 Category: Drugs & Pharmacology Source Type: research

Pulmonary Codelivery of Doxorubicin and siRNA by pH‐Sensitive Nanoparticles for Therapy of Metastatic Lung Cancer
In this study, DOX is conjugated onto polyethylenimine (PEI) by using cis‐aconitic anhydride (CA, a pH‐sensitive linker) to obtain PEI‐CA‐DOX conjugates. The PEI‐CA‐DOX/siRNA complex nanoparticles are formed spontaneously via electrostatic interaction between cationic PEI‐CA‐DOX and anionic siRNA. The drug release experiment shows that DOX releases faster at acidic pH than at pH 7.4. Moreover, PEI‐CA‐DOX/Bcl2 siRNA complex nanoparticles show higher cytotoxicity and apoptosis induction in B16F10 cells than those treated with either DOX or Bcl2 siRNA alone. When the codelivery systems are directly sprayed...
Source: Small - July 1, 2015 Category: Nanotechnology Authors: Caina Xu, Ping Wang, Jingpeng Zhang, Huayu Tian, Kinam Park, Xuesi Chen Tags: Full Paper Source Type: research

Cationic polyaspartamide-based nanocomplexes mediate siRNA entry and down-regulation of the pro-inflammatory mediator high mobility group box 1 in airway epithelial cells
In conclusion, we have found optimal conditions for down-regulation of HMGB1 by siRNA delivery mediated by polyaminoacidic polymers in airway epithelial cells in the absence of cytotoxicity. Functional and in-vivo studies are warranted. Graphical abstract
Source: International Journal of Pharmaceutics - July 11, 2015 Category: Drugs & Pharmacology Source Type: research

The intracellular pharmacodynamics of siRNA is responsible for the low gene silencing activity of siRNA-loaded nanoparticles in dendritic cells
Publication date: 15 October 2015 Source:International Journal of Pharmaceutics, Volume 494, Issue 1 Author(s): Takashi Nakamura, Yuki Fujiwara, Shota Warashina, Hideyoshi Harashima The delivery of small interfering RNA (siRNA) to dendritic cells (DCs) is a challenging issue for siRNA-loaded lipid nanoparticles. The cause of this difficulty is unknown. The findings reported herein indicate that the rate-limiting step in gene silencing using siRNA-loaded lipid nanoparticles in DCs, as evidenced by a quantitative analysis of each process in siRNA delivery between mouse bone marrow derived DC (BMDC) and other cell lines...
Source: International Journal of Pharmaceutics - August 26, 2015 Category: Drugs & Pharmacology Source Type: research

Intrathecal injection of phosphodiesterase 4B-specific siRNA attenuates neuropathic pain in rats with L5 spinal nerve ligation.
Authors: Ji Q, Di Y, He X, Liu Q, Liu J, Li W, Zhang L Abstract Phosphodiesterase 4 (PDE4) is an adenosine cyclic 3,5-monophosphate-specific degradative enzyme, which is closely associated with the inflammatory response. Among its four subtypes (A‑D), it remains unclear which one exerts suppressive effects on inflammation and reduces neuropathic pain. The present study aimed to examine the modulation of neuroinflammation by PDE4 subtypes in the spinal cord of a rat model of L5 spinal nerve ligation (SNL)‑induced neuropathic pain. The expression levels of PDE4A‑D were measured in the lumbar spinal cords of na...
Source: Molecular Medicine Reports - December 29, 2015 Category: Molecular Biology Tags: Mol Med Rep Source Type: research

Attenuating Ischemia-Reperfusion Injury in Kidney Transplantation by Perfusing Donor Organs With siRNA Cocktail Solution
Conclusions: In conclusion, this is the first demonstration that perfusing donor organs with an siRNA cocktail solution can induce gene silencing in the kidney and prevent kidneys from extended cold I/R injury in kidney transplantation, highlighting the promise of the clinical application of siRNA-based therapies in the preservation of donor organs.
Source: Transplantation - March 22, 2016 Category: Transplant Surgery Tags: Original Basic Science-General Source Type: research

ADAM17-siRNA inhibits MCF-7 breast cancer through EGFR-PI3K-AKT activation.
Abstract A disintegrin and metalloproteinase-17 (ADAM17) can cut and release a wide variety of epidermal growth factor receptor (EGFR) ligands to promote survival, invasion and proliferation of cancer cell, and therefore, is considered to be a potential therapeutic target for cancer. The main goal of the present study was to observe the effects of ADAM17 small interfering RNA (ADAM17-siRNA) on human MCF-7 breast cancer and investigate its activation pathway. In vitro, MCF-7 cells were divided into ADAM17-siRNA groups, nonsense siRNA groups, AG1478 (selective EGFR blocker) groups, LY294002 [phosphatidylinositol 3-...
Source: International Journal of Oncology - May 23, 2016 Category: Cancer & Oncology Authors: Meng X, Hu B, Hossain MM, Chen G, Sun Y, Zhang X Tags: Int J Oncol Source Type: research