Abstract

Upon sonication, the antimicrobial and antineoplastic compound dequalinium^TM forms vesicles (DQAsomes, Weissig et al., 1998). Dequalinium^TM (1,1′-(1,10-decamethylene-bis-[aminoquinaldinium])-chloride) was shown to be a fluorophore with an emission maximum at 366 nm. Addition of DNA results in a characteristic quenching of its intrinsic fluorescence. After density gradient centrifugation a band of dequalinium^TM (DQA) tightly associated with DNA is located between the DNA and DQA bands. DQA/DNA-complexes containing plasmid DNA at a molar ratio of DQA/DNA 6:1 are completely protected against DNase activity. Addition of negatively-charged lipids release intact DNA in the same manner as from cationic lipid/DNA complexes. As regards biological effects, DQAsomes show a differential cytotoxicity for normal and sarcoma cell lines. In vitro incubation with fluorescein-labeled oligodeoxynucleotides (5′-fluorescein-[GATC]₅) showed an increased uptake of the tagged oligodeoxynucleotide if complexed with dequalinium.

We hypothesize that the DQA/DNA complexes are well-suited for ‘DQAsomal gene transfer’ in vitro and in vivo. Noteworthy, they display an intrinsic antitumor activity manifested by differential cytotoxicity for normal and sarcoma cells.