TY - JOUR
T1 - Safety profile of dextran-spermine gene delivery vector in mouse lungs
AU - Yeo, Wendy Wai Yeng
AU - Hosseinkhani, Hossein
AU - Rahman, Sabariah A.
AU - Rosli, Rozita
AU - Domb, Abraham J.
AU - Abdullah, Syahril
PY - 2014/5
Y1 - 2014/5
N2 - 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-α, IL-12, IFN-γ 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.
AB - 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-α, IL-12, IFN-γ 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.
KW - Dextran-spermine
KW - Mouse lung
KW - Non-viral delivery
KW - Polymer
KW - Safety
UR - http://www.scopus.com/inward/record.url?scp=84897996836&partnerID=8YFLogxK
U2 - 10.1166/jnn.2014.8073
DO - 10.1166/jnn.2014.8073
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C2 - 24734548
AN - SCOPUS:84897996836
SN - 1533-4880
VL - 14
SP - 3328
EP - 3336
JO - Journal of Nanoscience and Nanotechnology
JF - Journal of Nanoscience and Nanotechnology
IS - 5
ER -