Hostname: page-component-586b7cd67f-gb8f7 Total loading time: 0 Render date: 2024-11-29T07:50:33.539Z Has data issue: false hasContentIssue false
  • English
  • Français

The Effects of Charge Separation in Quaternary Ammonium, DABCO-Containing Polymers on In Vitro Toxicity and Gene Delivery

Published online by Cambridge University Press:  01 February 2011

Theresa M. Reineke  and
Mark E. Davis
Theresa M. Reineke
Affiliation:
Division of Chemistry and Chemical Engineering, California Institute of Technology Pasadena, CA 91107, U.S.A.
Mark E. Davis
Affiliation:
Division of Chemistry and Chemical Engineering, California Institute of Technology Pasadena, CA 91107, U.S.A.
Get access

Abstract

Polycation materials have recently emerged as promising systems for the delivery of genetic material. In this study, several DABCO (1, 4-diazabicyclo[2.2.2]octane) polymers are investigated for their ability to bind and deliver plasmid DNA (pDNA) into mammalian cells. The DABCO polymers are synthesized by copolymerization of DABCO with 1, 3-dibromopropane (D3), 1, 4-dibromobutane (D4), 1, 6-dibromohexane (D6), 1, 8-dibromooctane (D8), and 1, 10-dibromodecane (D10) to form a series of quaternary ammonium polymers with increasing charge separation. Gel retardation experiments reveal that each polymer (D3-D10) binds pDNA above a charge ratio of 1.0 (polymer + / pDNA -). The polycations are examined for in vitro transfection efficiency and toxicity in BHK-21 cells. Results of the transfection experiments indicate that the D6 polymer had the highest transfection efficiency. Although all of the polymers are shown to have some toxicity, the D8 and D10 polymers are more toxic to BHK-21 cells; approximately 30% of the cells survive at a charge ratio of 5 +/- as compared to the D3, D4, and D6 polymers where survival rates are about 80%.

Type
Research Article
Information
MRS Online Proceedings Library (OPL) , Volume 724: Symposium N – Biological and Biomimetic Materials Properties to Function , 2002 , N10.2
Copyright
Copyright © Materials Research Society 2002

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Han, S., Mahato, R. I., Sung, Y. K., Kim, S. W., Molecular Therapy 2, 302–317 (2000).Google Scholar
2. Hwang, S. J., Davis, M. E., Curr. Opin. Mol. Ther. 3, 183–191 (2001).Google Scholar
3. Mahato, R. I., Smith, L. C., Rolland, A. P., Adv. Genet. 41, 95–156 (1999).Google Scholar
4. Ferruti, P., Manzoni, S., Richardson, S. C. W., Duncan, R., Pattrick, N. G., Mendichi, R., Casolaro, M., Macromolecules 33, 7793–7800 (2000).Google Scholar
5. Jones, N. A., Hill, I. R. C., Stolnik, S., Bignotti, F., Davis, S. S., Garnett, M. C., Biochim. Biophys. Acta 1517, 1–18 (2000).Google Scholar
6. Hwang, S. J., Bellocq, N. C., Davis, M. E., Bioconjugate Chem. 12, 280–290 (2001).Google Scholar
7. Tang, M. X., Szoka, F. C., Gene Therapy 4, 823–832 (1997).Google Scholar
8. Daniels, R. H., Kerr, G. T., Rollmann, L. D., J. Am. Chem. Soc. 100, 3097–3100 (1978).Google Scholar
9. Takewaki, T., Beck, L. W., Davis, M. E., Micropor. Mesopor. Mat. 33, 197–201 (1999).Google Scholar
10. Gonzalez, H., Hwang, S. J., Davis, M. E., Bioconjugate Chem. 10, 1068–1074 (1999).Google Scholar