Simple PEG modification of DNA aptamer based on copper ion coordination for tumor targeting.
A simple modification of a DNA aptamer with poly(ethylene glycol) (PEG) based on metal coordination was developed. N,N-bis(carboxymethyl)-L-lysine (NTA) of a metal chelate residue was chemically introduced to one terminus of PEG. The NTA-introduced PEG (PEG-NTA) chelated Cu(2+) ions form a Cu(2+)-chelated PEG (PEG-Cu). When PEG-Cu was mixed with a DNA aptamer of anti-tumor activity (AS1411) in aqueous solution, a complex of PEG-Cu and AS1411 based on metal coordination was formed. The complex inhibited in vitro tumor growth in a dose-dependent manner. A body distribution study with tumor-bearing mice revealed that PEG-Cu-AS1411 complexes injected intravenously had a significant longer lifetime in the blood circulation and 1.5-2.0-fold higher accumulation in the tumor tissue than free AS1411. Intravenous injection of complexes suppressed the in vivo growth of tumor mass to a significantly greater extent compared with that of free AS1411. The Cu(2+)-coordinated PEG modification is a simple and promising method to enhance accumulation of the aptamer in the tumor, resulting in the augmented anti-tumor effect.
Takafuji
Yoshimasa
Y
a Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Jo
Jun-ichiro
J
Tabata
Yasuhiko
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002413:Cations, Divalent / Q000737:chemistry; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry; D003300:Copper / Q000737:chemistry*; D004247:DNA; D004305:Dose-Response Relationship, Drug; D005260:Female; D007275:Injections, Intravenous; D008239:Lysine / Q000031:analogs & derivatives / Q000737:chemistry; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011092:Polyethylene Glycols / Q000737:chemistry*; D012996:Solutions; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D014867:Water / Q000737:chemistry
C097388:2-N,N-bis(carboxymethyl)lysine; D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D002413:Cations, Divalent; D002614:Chelating Agents; D012996:Solutions; D014867:Water; D011092:Polyethylene Glycols; D003300:Copper; D004247:DNA; D008239:Lysine