Transfection of cultured cells has been reported using complexes betwe
en DNA and spherical cationic polyamidoamine polymers (Starburst dendr
imers) that consist of primary amines on the surface and tertiary amin
es in the interior. The transfection activity of the dendrimers is dra
matically enhanced (> 50-fold) by heat treatment in a variety of solvo
lytic solvents, e.g., water or butanol. Such treatment induces signifi
cant degradation of the dendrimer at the amide linkage, resulting in a
heterodisperse population of compounds with molecular weights ranging
from the very low (<1500 Da) to several tens of kilodaltons. The comp
ound facilitating transfection is the high molecular weight component
of the degraded product and is denoted as a ''fractured'' dendrimer. T
ransfection activity is related both to the initial size of the dendri
mer and its degree of degradation. Fractured dendrimers exhibit an inc
reased apparent volume change as measured by an increase in the reduce
d viscosity upon protonation of the terminal amines as pH is reduced f
rom 10.5 to 7.2 whereas intact dendrimers do not. Dendrimers with defe
ctive branching have been synthesized and also have improved transfect
ion activity compared to that of the intact dendrimers. For a series o
f heat-treated dendrimers we observe a correlation between transfectio
n activity and the degree of flexibility, computed with a random cleav
age simulation of the degradation process. We suggest that the increas
ed transfection after the heating process is principally due to the in
crease in flexibility that enables the fractured dendrimer to be compa
ct when complexed with DNA and swell when released from DNA.