1. ¹School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore
2. ²Division of Cellular & Molecular Research, National Cancer Centre, Singapore

Correspondence: Dr KM Hui, Division of Cellular and Molecular Research, National Cancer Centre, 11 Hospital Drive, 169610 Singapore. E-mail: cmrhkm@nccs.com.sg

Received 28 August 2006; Revised 9 January 2007; Accepted 15 January 2007; Published online 8 March 2007.

Abstract

We have compared the ability of several nanosized bioceramic particles including negatively charged silica (SiO₂), neutrally charged hydroxyapatite (HA) and positively charged zirconia (ZrO₂) nanoparticles as non-viral vectors for efficient in vivo gene delivery. A mixture of highly monodispersed aqueous suspension of HA or SiO₂ nanoparticles, coated with protamine sulfate (PS), complexed efficiently with plasmid DNA and significantly enhanced transgene expression in vitro. In comparison, ZrO₂ nanoparticles gave poor transfection efficiency under similar conditions tested. It was also determined that, under the same conditions, PS-SiO₂-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-SiO₂-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-SiO₂-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- (IFN-). Most importantly, the injection of PS-SiO₂-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.