Long circulation of intravenously administered plasmid DNA delivered with dendritic poly(L-lysine) in the blood flow.
We previously showed that dendritic poly(L-lysine) of the 6th generation (KG6) had high transfection ability without significant cytotoxicity in vitro. Here, to evaluate the potential of KG6 as a nonviral gene carrier that works in vivo, we investigated the biodistribution of plasmid DNA delivered with KG6 in mice after intravenous administration, in comparison with DOTAP/Chol liposomes and PEI. Southern blotting analysis revealed that plasmid DNA complexes with KG6 at a C/A ratio of 8.0 circulated in the blood for 3 h after intravenous injection. The amounts of plasmid DNA in the liver gradually decreased. In tumor-bearing mice, plasmid DNA injected with KG6 was observed in the tumor at 60 min after the intravenous injection, while no DNA was present in the tumor using DOTAP/Chol liposomes. The stealth character of DNA complexes with KG6 in the blood would cause an enhanced permeability and retention (EPR) effect in the tumor. KG6 is expected to be a promising candidate that enables functional gene delivery in vivo.
Kawano
Takahito
T
Department of Materials Science, Graduate School of Science and Technology, Nagasaki University, Nagasaki 852-8521, Japan.
Okuda
Tatsuya
T
Aoyagi
Haruhiko
H
Niidome
Takuro
T
D000818:Animals; D001775:Blood Circulation / Q000502:physiology*; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D018014:Gene Transfer Techniques; D007275:Injections, Intravenous; D008546:Melanoma, Experimental; D051379:Mice; D009368:Neoplasm Transplantation / Q000379:methods; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics; D011107:Polylysine / Q000008:administration & dosage* / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors; D014162:Transfection / Q000379:methods
D005229:Fatty Acids, Monounsaturated; D000644:Quaternary Ammonium Compounds; D011107:Polylysine; D004247:DNA; D002784:Cholesterol; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane