J. Lasch et al., Dequalinium (TM) vesicles form stable complexes with plasmid DNA which areprotected from DNase attack, BIOL CHEM, 380(6), 1999, pp. 647-652
Upon sonication, the antimicrobial and antineoplastic compound dequaliniumT
M forms vesicles (DQAsomes, Weissig et al,, 1998), DequaliniumTM (1,1'-(1,1
0-decamethylene-bis-[aminoquinaldinium])-chloride) was shown to be a fluoro
phore with an emission maximum at 366 nm, Addition of DNA results in a char
acteristic quenching of its intrinsic fluorescence. After density gradient
centrifugation a band of dequaliniumTM (DQA) tightly associated with DNA is
located between the DNA and DQA bands. DQA/DNA-complexes containing plasmi
d DNA at a molar ratio of DQA/DNA 6:1 are completely protected against DNas
e activity. Addition of negatively-charged lipids release intact DNA in the
same manner as from cationic lipid/DNA complexes. As regards biological ef
fects, DQAsomes show a differential cytotoxicity for normal and sarcoma cel
l lines. In vitro incubation with fluorescein-labeled oligodeoxynucleotides
(5'-fiuorescein-[GATC](5)) showed an increased uptake of the tagged oligod
eoxynucleotide if complexed with dequalinium.
We hypothesize that the DQA/DNA complexes are well-suited for 'DQAsomal gen
e transfer' in vitro and in vivo. Noteworthy, they display an intrinsic ant
itumor activity manifested by differential cytotoxicity for normal and sarc
oma cells.