Gene expression in synovial membrane cells after intraarticular delivery of plasmid-linked superparamagnetic iron oxide particles - A preliminary study in sheep

Larry D Galuppo, Sarah W. Kamau, Benedikt Steitz, Paul O. Hassa, Monika Hilbe, Lloyd Vaughan, Sabine Koch, Alke Fink-Petri, Margarethe Hofman, Heinrich Hofman, Michael O. Hottiger, Brigitte Von Rechenberg

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

This study evaluated in vivo gene delivery and subsequent gene expression within cells of the synovium in the presence of static and pulsating magnetic field application following intraarticular injection of superparamagnetic iron oxide nanoparticles linked to plasmids containing reporter genes encoding for fluorescent proteins. Plasmids encoding genes for either green fluorescent protein or red fluorescent protein were bound to superparamagnetic nanoparticles coated with polyethyleneimine. Larger (200-250 nm) and smaller (50 nm) nanoparticles were compared to evaluate the effects of size on transfection efficiency as well as any associated intraarticular reaction. Comparisons between groups were evaluated at 24, 72, and 120 h time periods. Inflammatory response was mild to moderate for all injected particles, but was present in the majority of synovial membrane samples evaluated. Larger particles tended to be associated with more inflammation than smaller ones. Nevertheless, intraarticular application of both experimental and control nanoparticles were well tolerated clinically. Gene expression as determined by observation of either green or red intracellular fluorescence was difficult to assess by both epifluorescent light, and confocal microscopy. An insufficient concentration of nanoparticles in relation to joint volume likely resulted in a limited number of samples with positive evidence of iron staining and with suspected positive evidence of cells expressing fluorescent proteins. Our results indicate that intraarticular administration of functionalized superparamagnetic iron oxide nanoparticles resulted in a mild to moderate synovitis and there was in conclusive evidence of gene expression. Further research is warranted to determine the best and most effective reporter assay for assessment of the in vivo gene delivery into the joints. In addition, the best suited concentration and size of nanoparticles, which will optimize gene delivery and expression, while minimizing intraarticular inflammation, needs to be determined.

Original languageEnglish (US)
Pages (from-to)2841-2852
Number of pages12
JournalJournal of Nanoscience and Nanotechnology
Volume6
Issue number9-10
DOIs
StatePublished - Sep 2006
Externally publishedYes

Fingerprint

Synovial Membrane
Cell membranes
Iron oxides
Gene expression
Nanoparticles
Sheep
Plasmids
Gene Expression
Proteins
Gene encoding
Genes
Joints
Inflammation
Polyethyleneimine
Intra-Articular Injections
Synovitis
Confocal microscopy
Magnetic Fields
Green Fluorescent Proteins
ferric oxide

Keywords

  • Gene Delivery
  • Superparamagnetic Nanoparticles
  • Synovial Membrane

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Materials Science (miscellaneous)
  • Engineering (miscellaneous)

Cite this

Gene expression in synovial membrane cells after intraarticular delivery of plasmid-linked superparamagnetic iron oxide particles - A preliminary study in sheep. / Galuppo, Larry D; Kamau, Sarah W.; Steitz, Benedikt; Hassa, Paul O.; Hilbe, Monika; Vaughan, Lloyd; Koch, Sabine; Fink-Petri, Alke; Hofman, Margarethe; Hofman, Heinrich; Hottiger, Michael O.; Von Rechenberg, Brigitte.

In: Journal of Nanoscience and Nanotechnology, Vol. 6, No. 9-10, 09.2006, p. 2841-2852.

Research output: Contribution to journalArticle

Galuppo, LD, Kamau, SW, Steitz, B, Hassa, PO, Hilbe, M, Vaughan, L, Koch, S, Fink-Petri, A, Hofman, M, Hofman, H, Hottiger, MO & Von Rechenberg, B 2006, 'Gene expression in synovial membrane cells after intraarticular delivery of plasmid-linked superparamagnetic iron oxide particles - A preliminary study in sheep', Journal of Nanoscience and Nanotechnology, vol. 6, no. 9-10, pp. 2841-2852. https://doi.org/10.1166/jnn.2006.481
Galuppo, Larry D ; Kamau, Sarah W. ; Steitz, Benedikt ; Hassa, Paul O. ; Hilbe, Monika ; Vaughan, Lloyd ; Koch, Sabine ; Fink-Petri, Alke ; Hofman, Margarethe ; Hofman, Heinrich ; Hottiger, Michael O. ; Von Rechenberg, Brigitte. / Gene expression in synovial membrane cells after intraarticular delivery of plasmid-linked superparamagnetic iron oxide particles - A preliminary study in sheep. In: Journal of Nanoscience and Nanotechnology. 2006 ; Vol. 6, No. 9-10. pp. 2841-2852.
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AU - Hassa, Paul O.

AU - Hilbe, Monika

AU - Vaughan, Lloyd

AU - Koch, Sabine

AU - Fink-Petri, Alke

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AB - This study evaluated in vivo gene delivery and subsequent gene expression within cells of the synovium in the presence of static and pulsating magnetic field application following intraarticular injection of superparamagnetic iron oxide nanoparticles linked to plasmids containing reporter genes encoding for fluorescent proteins. Plasmids encoding genes for either green fluorescent protein or red fluorescent protein were bound to superparamagnetic nanoparticles coated with polyethyleneimine. Larger (200-250 nm) and smaller (50 nm) nanoparticles were compared to evaluate the effects of size on transfection efficiency as well as any associated intraarticular reaction. Comparisons between groups were evaluated at 24, 72, and 120 h time periods. Inflammatory response was mild to moderate for all injected particles, but was present in the majority of synovial membrane samples evaluated. Larger particles tended to be associated with more inflammation than smaller ones. Nevertheless, intraarticular application of both experimental and control nanoparticles were well tolerated clinically. Gene expression as determined by observation of either green or red intracellular fluorescence was difficult to assess by both epifluorescent light, and confocal microscopy. An insufficient concentration of nanoparticles in relation to joint volume likely resulted in a limited number of samples with positive evidence of iron staining and with suspected positive evidence of cells expressing fluorescent proteins. Our results indicate that intraarticular administration of functionalized superparamagnetic iron oxide nanoparticles resulted in a mild to moderate synovitis and there was in conclusive evidence of gene expression. Further research is warranted to determine the best and most effective reporter assay for assessment of the in vivo gene delivery into the joints. In addition, the best suited concentration and size of nanoparticles, which will optimize gene delivery and expression, while minimizing intraarticular inflammation, needs to be determined.

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