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Licensed Unlicensed Requires Authentication Published by De Gruyter June 1, 2005

Dequalinium TM Vesicles Form Stable Complexes with Plasmid DNA which Are Protected from DNase Attack

J. Lasch, A. Meye, H. Taubert, R. Koelsch, J. Mansa-ard and V. Weissig
From the journal Biological Chemistry

Abstract

Upon sonication, the antimicrobial and antineoplastic compound dequaliniumTM forms vesicles (DQAsomes, Weissig et al., 1998). DequaliniumTM (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 dequaliniumTM (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.

Published Online: 2005-6-1
Published in Print: 1999-6-1

Copyright © 1999 by Walter de Gruyter GmbH & Co. KG