TY - JOUR
T1 - The lower-generation polypropylenimine dendrimers are effective gene-transfer agents
AU - Zinselmeyer, B. H.
AU - Mackay, S. P.
AU - Schatzlein, A. G.
AU - Uchegbu, I. F.
N1 - Funding Information:
This work was part funded by a University of Strathclyde and University of Glasgow Synergy award to IFU and AGS and a Sir Henry Wellcome Award for Innovative Research to IFU.
PY - 2002
Y1 - 2002
N2 - Objective. To evaluate polypropylenimine dendrimers (generations 1-5: DAB 4, DAB 8, DAB 16, DAB 32, and DAB 64) as gene delivery systems. Methods. DNA binding was evaluated by measuring the reduced fluorescence of ethidium bromide, and molecular modelling of dendrimer-DNA complexes also was performed. Cell cytotoxicity was evaluated against the A431 cell line using the MTT assay. In vitro transfection was evaluated against the A431 cell line using the β-galactosidase reporter gene and N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulphate (DOTAP) served as a positive control. Results. Molecular modeling and experimental data revealed that DNA binding increased with dendrimer generation. Cell cytotoxicity was largely generation dependent, and cytotoxicity followed the trend DAB 64 > DAB 32 > DAB 16 > DOTAP > DAB 4 > DAB 8, whereas transfection efficacy followed the trend DAB 8 = DOTAP = DAB 16 > DAB 4 > DAB 32 = DAB 64. Conclusion. The generation 2 polypropylenimine dendrimer combines a sufficient level of DNA binding with a low level of cell cytoxicity to give it optimum in vitro gene transfer activity.
AB - Objective. To evaluate polypropylenimine dendrimers (generations 1-5: DAB 4, DAB 8, DAB 16, DAB 32, and DAB 64) as gene delivery systems. Methods. DNA binding was evaluated by measuring the reduced fluorescence of ethidium bromide, and molecular modelling of dendrimer-DNA complexes also was performed. Cell cytotoxicity was evaluated against the A431 cell line using the MTT assay. In vitro transfection was evaluated against the A431 cell line using the β-galactosidase reporter gene and N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulphate (DOTAP) served as a positive control. Results. Molecular modeling and experimental data revealed that DNA binding increased with dendrimer generation. Cell cytotoxicity was largely generation dependent, and cytotoxicity followed the trend DAB 64 > DAB 32 > DAB 16 > DOTAP > DAB 4 > DAB 8, whereas transfection efficacy followed the trend DAB 8 = DOTAP = DAB 16 > DAB 4 > DAB 32 = DAB 64. Conclusion. The generation 2 polypropylenimine dendrimer combines a sufficient level of DNA binding with a low level of cell cytoxicity to give it optimum in vitro gene transfer activity.
KW - Astramol
KW - Cytotoxicity
KW - Gene delivery
KW - Molecular modeling
KW - Polypropylenimine dendrimers
UR - http://www.scopus.com/inward/record.url?scp=0035997509&partnerID=8YFLogxK
U2 - 10.1023/A:1016458104359
DO - 10.1023/A:1016458104359
M3 - Article
C2 - 12180548
AN - SCOPUS:0035997509
SN - 0724-8741
VL - 19
SP - 960
EP - 967
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 7
ER -