Dendritic polyamines: simple access to new materials with defined treelike structures for application in nonviral gene delivery.
Polycationic dendrimers are interesting nonviral vectors for in vitro DNA delivery. We describe a simple approach to the synthesis of dendritic polyamines with different molecular weights and adjustable flexibility (degrees of branching; DB). Both parameters influence the transfection efficiency and the cell toxicity of the polymer. Functionalization of hyperbranched polyethylenimine (PEI) by a two-step procedure generated fully branched pseudodendrimers (analogues of polypropylenimine (PPI) and polyamidoamine (PAMAM) dendrimers). The DNA transfection efficiencies observed for these polymers depended on the cell line investigated. The highest efficiencies were observed for polymers whose unfunctionalized PEI cores had molecular weights in the range M(w)=6000-25 000 g mol(-1). The cytotoxicity of the dendrimers generally rises with increasing core size. The data collected for NIH/3T3 and COS-7 cells indicate a maximum transfection efficiency at around 60 % branching for the PPI analogues, and at a PEI-core molecular weight of M(w)=25 000 g mol(-1). PAMAM functionalization of PEI (M(w)=5000 and 21 000 g mol(-1)) leads to polymers with little or no cytotoxity in the cell lines investigated.
Freiburger Materialforschungszentrum und Institut für Makromolekulare Chemie, Universität Freiburg, Stefan-Meier-Strasse 21, 79104 Freiburg, Germany.
Michael
M
Krämer
Jean-François
JF
Stumbé
Günther
G
Grimm
Brigitte
B
Kaufmann
Ute
U
Krüger
Martin
M
Weber
Rainer
R
Haag
D000818:Animals; D019556:COS Cells; D018014:Gene Transfer Techniques; D051379:Mice; D015394:Molecular Structure; D008970:Molecular Weight; D041681:NIH 3T3 Cells; D011073:Polyamines / Q000737:chemistry*
D011073:Polyamines