Anjuman Ara Begum,*1,2 Peter M. Moyleand Istvan Toth1,2,3

 

1School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland, Australia;

2School of Pharmacy, The University of Queensland, Woolloongabba, Queensland, Australia;

3Institute of Molecular Bioscience, The University of Queensland, St Lucia, Queensland, Australia.

 

The development of a safe and efficient gene delivery system is highly important. Several non-viral strategies have been investigated which includes peptides, polymer and liposome. Here a peptide/liposome hybrid system has been developed for target specific delivery of DNA.  A multicomponent peptide system, R9K(GALA)-BBN(6-14) has been synthesized successfully, using bombesin peptide (BBN(6-14), a gastrin releasing peptide receptor ligand for receptor mediated gene delivery ; cationic nona-arginine (R9) to bind and condense oligonucleotides, endosomal disrupting peptide to assist endosomal release. A DOTAP/DOPE containing liposome has been formulated and combined with the peptide system to investigate their effect on DNA delivery and gene expression. This liposome/peptide hybrid system has demonstrated higher eGFP expression compared to their polyplex or lipoplex equivalents. Peptide/DNA polyplexes showed better cellular uptake than liposome/DNA lipoplex formulations, however, on the contrary showed poor transgene expression. This might be due to that, liposome/DNA nanocomplexes promote endosomal release and higher availability of DNA for transgene expression. Besides, while liposome/DNA complexes showed comparatively higher toxic effect (MTT assay) than peptide/DNA complexes, the combined peptide/liposome/DNA showed minimal cytotoxic effect. This Peptide/liposome system has demonstrated synergistic effect on higher cellular uptake and transgene expression, target specificity of the system towards GRPR, lower cytotoxic effect and optimal endosomal release, thus suggesting its potential for target specific DNA delivery system.

 

Biographic Details

Name: Anjuman Ara Begum

Title: Mrs

Affiliation,Country:PhD student, UQ, Australia

Phone: +61470426842

E-mail: anjuman.begum@uq.net.au

Research interests: Drug/Gene delivery, nanomedicine,  molecular biology

Venue

Room: 
AEB 313