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.
Mamede
Marcelo
M
Department of Nuclear Medicine and Diagnostic Imaging, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Saga
Tsuneo
T
Ishimori
Takayoshi
T
Higashi
Tatsuya
T
Sato
Noriko
N
Kobayashi
Hisataka
H
Brechbiel
Martin W
MW
Konishi
Junji
J
D000818:Animals; D001360:Avidin / Q000737:chemistry*; D002614:Chelating Agents; D004247:DNA / Q000008:administration & dosage* / Q000493:pharmacokinetics; D050091:Dendrimers; D004337:Drug Carriers; D005260:Female; D018014:Gene Transfer Techniques; D022781:Hepatocytes / Q000378:metabolism*; D007205:Indium Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000493:pharmacokinetics; D011073:Polyamines / Q000737:chemistry; D014018:Tissue Distribution
D002614:Chelating Agents; D050091:Dendrimers; D004337:Drug Carriers; D007205:Indium Radioisotopes; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; C104700:PAMAM Starburst; D011073:Polyamines; D001360:Avidin; D004247:DNA