Hepatocyte targeting of 111In-labeled oligo-DNA with avidin or avidin-dendrimer complex

To establish an effective nonviral gene transfer vector to hepatocytes, various oligo-carrier complexes were developed employing dendrimer (G4) and avidin-biotin systems (Av-bt), and their biodistribution were evaluated. In-111-labeled-oligo, without any carriers, showed low uptake in normal organs other than the kidney (21.48% ID/g at 15 min, 18.48% ID/g at 60 min). In contrast, 111In-oligo coupled with avidin through biotin (111In-oligo-bt-Av) showed very high accumulation in the liver (50.95% at 15 min, 47.88% at 60 min). 111In-oligo complexed with G4 showed high uptake in the kidney and spleen, but its hepatic uptake was relatively low (13.12% at 15 min, 10.67% at 60 min). When both G4 and Av-bt systems were employed, 111In-oligo/G4-bt-Av showed extremely high uptake in the lung (182.33% at 15 min, 125.54% at 60 min), probably due to the formation of large molecular weight complex and aggregates which are trapped in the lung, and its hepatic uptake was lower than 111In-oligo-bt-Av. 111In-oligo-bt-Av, which exhibited the highest hepatic uptake in vivo, also showed high and rapid internalization into hepatocytes. The avidin-biotin system seems to have potential as a carrier of oligo-DNA to the liver.