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 Cu²⁺ ions form a Cu²⁺-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 Cu²⁺-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.