Dequalinium (TM) vesicles form stable complexes with plasmid DNA which areprotected from DNase attack

Citation
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
Citations number
13
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOLOGICAL CHEMISTRY
ISSN journal
14316730 → ACNP
Volume
380
Issue
6
Year of publication
1999
Pages
647 - 652
Database
ISI
SICI code
1431-6730(199906)380:6<647:D(VFSC>2.0.ZU;2-H
Abstract
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.