Biomaterial Database

Cyclodextrin-containing polymer delivery system for light-directed siRNA gene silencing. 2010

Sigurd Leinaes Bøe, and Ane Sager Longva, and Eivind Hovig

Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo, Norway. sigurdbo@rr-research.no

In this study, we have investigated the possibility of combining a cyclodextrin-containing polymer (CDP) with siRNA molecules to modulate gene expression in a light-directed manner through photochemical internalization (PCI) technology. We utilized S100A4 as a model gene to evaluate the efficacy of gene silencing. After optimization of carrier/cargo ratio and illumination dose, real-time reverse transcriptase-polymerase chain reaction data showed between 80% and 90% silencing in the siRNA samples treated with PCI compared with untreated control. In contrast, only a 0%-10% silencing effect was detected in the siRNA samples without PCI treatment, demonstrating the potency of light-specific delivery of siRNA molecules. Light-directed siRNA delivery was shown in 2 different cell lines with corresponding potency. Further, time-lapse results demonstrated maximum gene silencing only at 5 hours after endosomal release, implying, for example, rapid carrier decondensation when using the CDP. This work represents a first success in using a CDP delivery agent, without endosomolytic properties for siRNA gene silencing in a light-directed manner, opening the opportunity to use CDPs for light-directed siRNA gene silencing in vivo.

UI	MeSH Term	Description	Entries
D008027	Light	That portion of the electromagnetic spectrum in the visible, ultraviolet, and infrared range.	Light, Visible,Photoradiation,Radiation, Visible,Visible Radiation,Photoradiations,Radiations, Visible,Visible Light,Visible Radiations
D008247	Lysosomes	A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes MEMBRANE FUSION. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed).	Autolysosome,Autolysosomes,Lysosome
D009418	S100 Proteins	A family of highly acidic calcium-binding proteins found in large concentration in the brain and believed to be glial in origin. They are also found in other organs in the body. They have in common the EF-hand motif (EF HAND MOTIFS) found on a number of calcium binding proteins. The name of this family derives from the property of being soluble in a 100% saturated ammonium sulfate solution.	Antigen S 100,Nerve Tissue Protein S 100,S100 Protein,S-100 Protein,S100 Protein Family,Protein, S100,S 100 Protein
D011108	Polymers	Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., BIOPOLYMERS; PLASTICS).	Polymer
D011992	Endosomes	Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface.	Receptosomes,Endosome,Receptosome
D002470	Cell Survival	The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.	Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002482	Cellulose	A polysaccharide with glucose units linked as in CELLOBIOSE. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations.	Alphacel,Avicel,Heweten,Polyanhydroglucuronic Acid,Rayophane,Sulfite Cellulose,alpha-Cellulose,Acid, Polyanhydroglucuronic,alpha Cellulose
D003505	Cyclodextrins	A homologous group of cyclic GLUCANS consisting of alpha-1,4 bound glucose units obtained by the action of cyclodextrin glucanotransferase on starch or similar substrates. The enzyme is produced by certain species of Bacillus. Cyclodextrins form inclusion complexes with a wide variety of substances.	Cycloamylose,Cyclodextrin,Cyclodextrin Derivatives,Cyclomaltooligosaccharides,Derivatives, Cyclodextrin
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071999	S100 Calcium-Binding Protein A4	An S100 protein characterized by four helix bundles that form N- and C-terminal EF HAND MOTIFS. It functions as a homodimer and interacts with both intracellular and extracellular signaling proteins. Aberrant S100A4 activity is associated with NEOPLASM METASTASIS; FIBROSIS; and RHEUMATOID ARTHRITIS.	Calvasculin Protein,Fibroblast-Specific Protein 1,Metastasin Protein,Placental Calcium-Binding Protein,S100A4 Protein,Calcium-Binding Protein, Placental,Fibroblast Specific Protein 1,Placental Calcium Binding Protein,S100 Calcium Binding Protein A4