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siRNA Delivery (sirna + delivery)

Distribution by Scientific Domains

Polymers and Materials Science	57%
Chemistry	42%

Selected Abstracts

Biodegradable Dextran Nanogels for RNA Interference: Focusing on Endosomal Escape and Intracellular siRNA Delivery

ADVANCED FUNCTIONAL MATERIALS, Issue 9 2009
Koen Raemdonck
Abstract The successful therapeutic application of small interfering RNA (siRNA) largely relies on the development of safe and effective delivery systems that are able to guide the siRNA therapeutics to the cytoplasm of the target cell. In this report, biodegradable cationic dextran nanogels are engineered by inverse emulsion photopolymerization and their potential as siRNA carriers is evaluated. The nanogels are able to entrap siRNA with a high loading capacity, based on electrostatic interaction. Confocal microscopy and flow cytometry analysis reveal that large amounts of siRNA-loaded nanogels can be internalized by HuH-7 human hepatoma cells without significant cytotoxicity. Following their cellular uptake, it is found that the nanogels are mainly trafficked towards the endolysosomes. The influence of two different strategies to enhance endosomal escape on the extent of gene silencing is investigated. It is found that both the application of photochemical internalization (PCI) and the use of an influenza-derived fusogenic peptide (diINF-7) can significantly improve the silencing efficiency of siRNA-loaded nanogels. Furthermore, it is shown that an efficient gene silencing requires the degradation of the nanogels. As the degradation kinetics of the nanogels can easily be tailored, these particles show potential for intracellular controlled release of short interfering RNA. [source]

PEGylated Calcium Phosphate Nanocomposites as Smart Environment-Sensitive Carriers for siRNA Delivery

ADVANCED MATERIALS, Issue 34 2009
Mingzhen Zhang
A novel inorganic,organic hybrid nanocomposite is formed in situ using a simple and straightforward method. Conjugate of short interfering RNA (siRNA) duplex with poly(ethylene glycol) via a disulfide linkage (PEG,SS,siRNA) is demonstrated to regulate the crystal growth of calcium phosphate (CaP), yielding a monodispersed nanocomposite. The resultant nanocomposite can be utilized as nanocarriers for siRNA delivery. [source]

Selective Inhibition of Human Brain Tumor Cells through Multifunctional Quantum-Dot-Based siRNA Delivery,

ANGEWANDTE CHEMIE, Issue 1 2010
Jongjin Jung
Auf den Punkt gebracht: Quantenpunkte (QDs), die mit thiolmodifizierter small interfering RNA (siRNA) konjugiert sind, wurden mit thiolmodifizierten RGD- und HIV-Tat-Peptiden funktionalisiert. Diese multifunktionellen QDs wurden für den zielgerichteten Transport und die Verfolgung von siRNA-Molekülen zum Knockdown des für EGFRvIII kodierenden Gens genutzt, was zur Herunterregulierung des PI3K-Akt-Signalwegs und zur Apoptose maligner Gehirntumorzellen führte. [source]

PAMAM Dendrimers Mediate siRNA Delivery to Target Hsp27 and Produce Potent Antiproliferative Effects on Prostate Cancer Cells

CHEMMEDCHEM, Issue 8 2009
Xiao-xuan Liu
Abstract RNA interference (RNAi) holds great promise for the treatment of inherited and acquired diseases, provided that safe and efficient delivery systems are available. Herein we report that structurally flexible triethanolamine (TEA) core PAMAM dendrimers are able to deliver an Hsp27 siRNA effectively into prostate cancer (PC-3) cells by forming stable nanoparticles with siRNA, protecting the siRNA nanoparticles from enzymatic degradation, and enhancing cellular uptake of siRNA. The Hsp27 siRNA resulted in potent and specific gene silencing of heat-shock protein,27, an attractive therapeutic target in castrate-resistant prostate cancer. Silencing of the hsp27 gene led to induction of caspase-3/7-dependent apoptosis and inhibition of PC-3 cell growth in,vitro. In addition, the siRNA,dendrimer complexes are non-cytotoxic under the conditions used for siRNA delivery. Altogether, TEA core PAMAM dendrimer-mediated siRNA delivery, in combination with RNAi that specifically targets Hsp27, may constitute a promising approach for combating castrate-resistant prostate cancer, for which there is no efficacious treatment. [source]

Dextran Microgels for Time-Controlled Delivery of siRNA,

ADVANCED FUNCTIONAL MATERIALS, Issue 7 2008
Koen Raemdonck
Abstract To apply siRNA as a therapeutic agent, appropriate attention should be paid to the optimization of the siRNA gene silencing effect, both in terms of magnitude and duration. Intracellular time-controlled siRNA delivery could aid in tailoring the kinetics of siRNA gene knockdown. However, materials with easily tunable siRNA release properties have not been subjected to thorough investigation thus far. This report describes cationic biodegradable dextran microgels which can be loaded with siRNA posterior to gel formation. Even though the siRNAs are incorporated in the hydrogel network based on electrostatic interaction, still a time-controlled release can be achieved by varying the initial network density of the microgels. To demonstrate the biological functionality of the siRNA loaded gels, we studied their cellular internalization and enhanced green fluorescent protein (EGFP) gene silencing potential in HUH7 human hepatoma cells. [source]