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An immobilized nanoparticle-based platform for efficient gene knockdown of targeted cells in the circulation.(ORIGINAL ARTICLE)(Report)

It is well established that specific interaction between adhesion molecules of endothelial cells and receptors on leukocytes can separate and recruit leukocytes from the bloodstream to sites of inflammation and coagulation. Previously, we showed that P-selectin can be absorbed onto the surface of a... Full description

Journal Title: Gene Therapy Oct, 2009, Vol.16(10), p.1271(12)
Main Author: Huang, Z.
Other Authors: King, M. R.
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0969-7128
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recordid: gale_ofa210591690
title: An immobilized nanoparticle-based platform for efficient gene knockdown of targeted cells in the circulation.(ORIGINAL ARTICLE)(Report)
format: Article
creator:
  • Huang, Z.
  • King, M. R.
subjects:
  • Gene Therapy -- Health Aspects
  • Gene Therapy -- Research
  • Nanoparticles -- Usage
  • Rna Interference -- Research
  • White Blood Cells -- Physiological Aspects
  • White Blood Cells -- Genetic Aspects
  • White Blood Cells -- Research
ispartof: Gene Therapy, Oct, 2009, Vol.16(10), p.1271(12)
description: It is well established that specific interaction between adhesion molecules of endothelial cells and receptors on leukocytes can separate and recruit leukocytes from the bloodstream to sites of inflammation and coagulation. Previously, we showed that P-selectin can be absorbed onto the surface of a blood-compatible microrenathane tube, and the P-selectin-coated surface could successfully capture P-selectin receptor-positive stem cells from physiological shear flow in vitro and from the bloodstream in vivo. In this paper, P-selectin was covalently attached to the surface of nanoscale liposomes to create targeting nanoparticles (NPs). Small interfering RNA (siRNA) was encapsulated by these nanoscale liposomes, and the liposomes were stabilized by PEGylation with DSPE-PEG2000. Experiments showed that these P-selectin-, PEGylated-, nanoscale-liposomes (PS-DSPE-PEG NPs) could be absorbed onto the inner surface of microrenathane tubing. The coated surface could specifically capture targeted cells from physiological shear flow, efficiently deliver encapsulated siRNA into adherent cells and dramatically silence the targeted gene neutrophil elastase. With this device, we create a high localized concentration for siRNA delivery in the circulatory system, providing circulating target cells adequate time to interact with therapeutic materials. SiRNA is efficaciously delivered into specific target cells, thereby providing a powerful tool for highly efficient siRNA transfection and other therapeutic materials delivery in circulation. The method should prove especially useful for diseases derived from disorders of blood cells. doi:10.1038/gt.2009.76; published online 25 June 2009 Keywords: P-selectin; PEGylation; liposomes; target nanoparticles; siRNA delivery device
language: English
source:
identifier: ISSN: 0969-7128
fulltext: fulltext
issn:
  • 0969-7128
  • 09697128
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titleAn immobilized nanoparticle-based platform for efficient gene knockdown of targeted cells in the circulation.(ORIGINAL ARTICLE)(Report)
creatorHuang, Z. ; King, M. R.
ispartofGene Therapy, Oct, 2009, Vol.16(10), p.1271(12)
identifierISSN: 0969-7128
subjectGene Therapy -- Health Aspects ; Gene Therapy -- Research ; Nanoparticles -- Usage ; Rna Interference -- Research ; White Blood Cells -- Physiological Aspects ; White Blood Cells -- Genetic Aspects ; White Blood Cells -- Research
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descriptionIt is well established that specific interaction between adhesion molecules of endothelial cells and receptors on leukocytes can separate and recruit leukocytes from the bloodstream to sites of inflammation and coagulation. Previously, we showed that P-selectin can be absorbed onto the surface of a blood-compatible microrenathane tube, and the P-selectin-coated surface could successfully capture P-selectin receptor-positive stem cells from physiological shear flow in vitro and from the bloodstream in vivo. In this paper, P-selectin was covalently attached to the surface of nanoscale liposomes to create targeting nanoparticles (NPs). Small interfering RNA (siRNA) was encapsulated by these nanoscale liposomes, and the liposomes were stabilized by PEGylation with DSPE-PEG2000. Experiments showed that these P-selectin-, PEGylated-, nanoscale-liposomes (PS-DSPE-PEG NPs) could be absorbed onto the inner surface of microrenathane tubing. The coated surface could specifically capture targeted cells from physiological shear flow, efficiently deliver encapsulated siRNA into adherent cells and dramatically silence the targeted gene neutrophil elastase. With this device, we create a high localized concentration for siRNA delivery in the circulatory system, providing circulating target cells adequate time to interact with therapeutic materials. SiRNA is efficaciously delivered into specific target cells, thereby providing a powerful tool for highly efficient siRNA transfection and other therapeutic materials delivery in circulation. The method should prove especially useful for diseases derived from disorders of blood cells. doi:10.1038/gt.2009.76; published online 25 June 2009 Keywords: P-selectin; PEGylation; liposomes; target nanoparticles; siRNA delivery device
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