Abstract
The purpose of this study is to evaluate in vitro gene transfer activity of polyamidoamine (PAMAM) starburst dendrimer (generation 3, G3) conjugate with α-cyclodextrin (α-CDE conjugate (G3)) bearing mannose (Man-α-CDE conjugate (G3)) with the degree of substitution of the mannose moiety 10 (DSM 10) as a novel non-viral vector in NIH3T3 and HepG2 cells. Man-α-CDE conjugate (G3) was found to have much higher gene transfer activity than dendrimer and α-CDE conjugate in NIH3T3 and HepG2 cells, which are independent of the expression of cell-surface mannose receptors. Gene transfer activity of Man-α-CDE conjugate (G3) was highly serum-resistant compared to that of dendrimer and α-CDE conjugate. No cytotoxicity after transfection of the complex of pDNA with Man-α-CDE conjugate (G3) was observed and the transfection activity was much higher than Lipofectin® in NIH3T3 cells. These results suggest the potential use of Man-α-CDE conjugate (G3) as a non-viral vector.
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Abbreviations
- α-CDE conjugate:
-
dendrimer conjugate with α-cyclodextrin
- DSM:
-
the degree of substitution of the mannose moiety
- FCS:
-
fetal calf serum
- G:
-
generation
- Man-α-CDE conjugate:
-
α-CDE conjugate bearing mannose
- PAMAM:
-
polyamidoamine
- pDNA:
-
plasmid DNA
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Acknowledgements
This work was partially supported by a Grant-in-Aid from Tokyo Biochemical Research Foundation, a Grant-in-Aid from the Research Foundation for Pharmaceutical Sciences, a Grant-in-Aid for Encouragement of Young Scientists from the Ministry of Education, Science and Culture of Japan (12771464) and a Grant-in-Aid for Scientific Research (C) from Japan Society for the Promotion of Science (14572158).
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Chihara, Y., Arima, H., Arizono, M. et al. Serum-resistant Gene Transfer Activity of Mannosylated Dendrimer/α-Cyclodextrin Conjugate (G3). J Incl Phenom Macrocycl Chem 56, 89–93 (2006). https://doi.org/10.1007/s10847-006-9067-4
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DOI: https://doi.org/10.1007/s10847-006-9067-4