(645e) Targeted Co-Delivery of Drug and Gene with Self-Assembled Galactosylated Amphiphilic Oligopeptide Nanostructures for Cancer Treatment
AIChE Annual Meeting
2009
2009 Annual Meeting
Materials Engineering and Sciences Division
Biomaterials for Drug Delivery IV
Friday, November 13, 2009 - 9:50am to 10:10am
Wrong-site delivery of highly potent anticancer therapeutics has been one of the major drawbacks in current chemotherapy. In this study, we focused on delivery of drug and gene with cationic micelles self-assembled from amphiphilic oligopeptides. The delivery system targets the asialoglycoprotein receptor (ASGPR), which is over-expressed in most human liver carcinoma cell lines, by attaching a ligand onto the cationic surface of the micelles via electrostatic adsorption of a negatively-charged glycopeptide sequence containing galactose moiety. The attachment of the ligand onto the micelles was confirmed through dynamic light scattering technique as an increase in the hydrodynamic diameter of the micelle/DNA complexes was observed after the ligand attachment. Doxorubicin and luciferase-encoding plasmid were used as the model drug and gene to prove the concept. The uptake of these molecules by the human liver carcinoma HepG2 (ASGPR +) and human lung adenocarcinoma A549 (ASGPR -) cell lines was further evaluated through flow cytometry, confocals, and gene expression studies. Further, therapeutic p53-encoding plasmid was co-delivered with doxorubicin to achieve synergistic effect in suppressing cancer cell proliferation.