Nanosized bioceramic particles could function as efficient gene delivery vehicles with target specificity for the spleen

We have compared the ability of several nanosized bioceramic particles including negatively charged silica (SiO 2 ), neutrally charged hydroxyapatite (HA) and positively charged zirconia (ZrO 2 ) nanoparticles as non-viral vectors for efficient in vivo gene delivery. A mixture of highly monodisperse...

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Veröffentlicht in:	Gene therapy Jg. 14; H. 10; S. 828 - 835
Hauptverfasser:	Tan, K, Cheang, P, Ho, I A W, Lam, P Y P, Hui, K M
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 01.05.2007 Nature Publishing Group
Schlagworte:	Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Applied cell therapy and gene therapy Biocompatible Materials Biological and medical sciences Biological assay Biomedical and Life Sciences Biomedicine Biotechnology Cell Biology Cell Line, Tumor Ceramics in medicine Deoxyribonucleic acid DNA Female Fundamental and applied biological sciences. Psychology Gene Expression Gene Therapy Gene transfer Genetic Therapy - methods Health aspects Health. Pharmaceutical industry Human Genetics Humans Hydroxyapatite Immune response Industrial applications and implications. Economical aspects Injection Interferon-gamma - blood Interleukin 2 Interleukin-2 - blood Liposomes Luciferases - genetics Medical sciences Melanoma, Experimental Membrane Proteins - blood Methods Mice Mice, Inbred BALB C Microscopy, Confocal Microscopy, Electron Nanoparticles Nanotechnology Neoplasms - immunology Neoplasms - metabolism Neoplasms - therapy original-article Protamine sulfate Silicon dioxide Spleen Spleen - metabolism Transfection Transfection - methods Transfusions. Complications. Transfusion reactions. Cell and gene therapy Tumor cells Zirconia γ-Interferon Singapore tumor-specific immune responses nanoplexes spleen nano-bioceramics particles silica non-viral vector Particle Spleen Specificity Immune response Tumor Gene therapy Vector
ISSN:	0969-7128, 1476-5462
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Zusammenfassung:	We have compared the ability of several nanosized bioceramic particles including negatively charged silica (SiO 2 ), neutrally charged hydroxyapatite (HA) and positively charged zirconia (ZrO 2 ) nanoparticles as non-viral vectors for efficient in vivo gene delivery. A mixture of highly monodispersed aqueous suspension of HA or SiO 2 nanoparticles, coated with protamine sulfate (PS), complexed efficiently with plasmid DNA and significantly enhanced transgene expression in vitro . In comparison, ZrO 2 nanoparticles gave poor transfection efficiency under similar conditions tested. It was also determined that, under the same conditions, PS-SiO 2 -DNA, but not PS-HA-DNA-nanoplexes, were able to mediate efficient transgene expression in vitro in the presence of 50% serum. Intraperitoneal injections of PS-SiO 2 -luciferase DNA nanoplexes targeted the highest level of transgene expression in the spleen of recipient mice that lasted for more than 48 h. Injection of PS-SiO 2 -pNGVL-hFLex-MUC-1 nanoplexes was able to mediate the production of Flt-3L in the sera of recipient mice. Simultaneously, the production of Flt-3L was accompanied by the stimulation of IL-2 and interferon- γ (IFN- γ ). Most importantly, the injection of PS-SiO 2 -pNGVL-hFLex-MUC-1 nanoplexes could mount potent anti-tumour specific immune responses that led to the subsequent regression of parental tumor cells containing the muc-1 determinant.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0969-7128 1476-5462
DOI:	10.1038/sj.gt.3302937