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 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-gamma (IFN-gamma). 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.
Tan
K
K
1School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
Cheang
P
P
Ho
I A W
IA
Lam
P Y P
PY
Hui
K M
KM
D000818:Animals; D001672:Biocompatible Materials; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D008081:Liposomes; D008156:Luciferases / Q000235:genetics; D008546:Melanoma, Experimental; D008565:Membrane Proteins / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D053758:Nanoparticles; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D013154:Spleen / Q000378:metabolism*; D014162:Transfection / Q000379:methods*
D001672:Biocompatible Materials; D007376:Interleukin-2; D008081:Liposomes; D008565:Membrane Proteins; C084881:flt3 ligand protein; D007371:Interferon-gamma; D008156:Luciferases