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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| Published in: | Gene therapy Vol. 14; no. 10; pp. 828 - 835 |
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| Main Authors: | , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
London
Nature Publishing Group UK
01.05.2007
Nature Publishing Group |
| Subjects: | |
| ISSN: | 0969-7128, 1476-5462 |
| Online Access: | Get full text |
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| Summary: | 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. |
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| Bibliography: | 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 |