Safety profile of dextran-spermine gene delivery vector in mouse lungs
| Autor: | Syahrilnizam Abdullah, Hossein Hosseinkhani, Abraham J. Domb, Wendy Wai Yeng Yeo, Rozita Rosli, Sabariah Abdul Rahman |
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| Rok vydání: | 2014 |
| Předmět: |
Biodistribution
Materials science Genetic Vectors Biomedical Engineering Bioengineering Enzyme-Linked Immunosorbent Assay Gene delivery Mice In vivo Chlorocebus aethiops Dextrins medicine Animals General Materials Science Tissue Distribution Lung Mice Inbred BALB C medicine.diagnostic_test fungi General Chemistry Transfection Condensed Matter Physics Molecular biology Bronchoalveolar lavage medicine.anatomical_structure Toxicity COS Cells MCF-7 Cells Nasal administration Female Spermine Bronchoalveolar Lavage Fluid Plasmids |
| Zdroj: | Journal of nanoscience and nanotechnology. 14(5) |
| ISSN: | 1533-4880 |
| Popis: | A nano-sized polymer, dextran-spermine (D-SPM), was shown to have the capacity to deliver gene to the lung of mouse via intranasal route. In this study, assessments on the safety profile of D-SPM were performed to complement the gene expression results. African green monkey kidney fibroblast (COS-7) and human adenocarcinoma breast (MCF-7) cells transfected with D-SPM/pDNA showed massive reduction in the number of viable cells. As for in vivo study, elevated level of neutrophils was observed, despite the minimal level of pro-inflammatory cytokines (TNF-alpha, IL-12, IFN-gamma) detected in the bronchoalveolar lavage fluid (BALF) of mice treated with the D-SPM/pDNA complexes. Histology profile examinations of the lungs showed mild inflammatory responses, with inflamed areas overlap with healthy areas. Although reduction of mice weight was seen at day 1 post administration, the mice did not show any sign of abnormal behavior or physical appearance. Biodistribution study was performed to determine the ability of the D-SPM/pDNA complexes to infiltrate to other non-intended organs. The result showed that the D-SPM/pDNA complexes were only localized at the lung and no gene expression was detected in other organs or blood. In short, these results indicate that the D-SPM/pDNA exhibited mild toxicity in the mouse lungs. |
| Databáze: | OpenAIRE |
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