title: Gene transfer into the lung by nanoparticle dextran-spermine/plasmid DNA complexes.
abstract: A novel cationic polymer, dextran-spermine (D-SPM), has been found to mediate gene expression in a wide variety of cell lines and in vivo through systemic delivery. Here, we extended the observations by determining the optimal conditions for gene expression of D-SPM/plasmid DNA (D-SPM/pDNA) in cell lines and in the lungs of BALB/c mice via instillation delivery. In vitro studies showed that D-SPM could partially protect pDNA from degradation by nuclease and exhibited optimal gene transfer efficiency at D-SPM to pDNA weight-mixing ratio of 12. In the lungs of mice, the levels of gene expression generated by D-SPM/pDNA are highly dependent on the weight-mixing ratio of D-SPM to pDNA, amount of pDNA in the complex, and the assay time postdelivery. Readministration of the complex at day 1 following the first dosing showed no significant effect on the retention and duration of gene expression. The study also showed that there was a clear trend of increasing size of the complexes as the amount of pDNA was increased, where the sizes of the D-SPM/pDNA complexes were within the nanometer range.
authors.affiliation: UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. syahril@medic.upm.edu.my
authors.forename: Syahril
authors.initials: S
authors.lastname: Abdullah
authors.forename: Wai Yeng
authors.initials: WY
authors.lastname: Wendy-Yeo
authors.forename: Hossein
authors.initials: H
authors.lastname: Hosseinkhani
authors.forename: Mohsen
authors.initials: M
authors.lastname: Hosseinkhani
authors.forename: Ehab
authors.initials: E
authors.lastname: Masrawa
authors.forename: Rajesh
authors.initials: R
authors.lastname: Ramasamy
authors.forename: Rozita
authors.initials: R
authors.lastname: Rosli
authors.forename: Sabariah A
authors.initials: SA
authors.lastname: Rahman
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Domb
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004247:DNA; D003850:Deoxyribonuclease I; D003911:Dextrans / Q000737:chemistry*; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D008156:Luciferases; D008168:Lung / Q000378:metabolism*; D046911:Macromolecular Substances; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D010316:Particle Size; D010957:Plasmids / Q000235:genetics*; D013096:Spermine / Q000737:chemistry*
chemical_list: D003911:Dextrans; D046911:Macromolecular Substances; D013096:Spermine; D004247:DNA; D008156:Luciferases; D003850:Deoxyribonuclease I