Master of Science
Dr. John Lewis
Prostate cancer is the most common malignancy in North American men and there is no treatment currently available which offers a clear survival advantage to patients with prostate cancer. We studied liposomes formulated with the fusion-associated small transmembrane (FAST) protein, p14. In this study, we hypothesized that therapeutics delivered in molecular targeted fusogenic liposomes will increase intracellular delivery and specificity for prostate cancer. We demonstrated that liposomes formulated with p14-bombesin significantly increased the delivery of fluorescein isothiocyanate (FITC) into human prostate cancer (PC-3) cells compared to either standard liposomes or non-targeted fusogenic liposomes. Delivery of FITC to benign prostate hyperplasia (BPH) cells, which express low levels of the gastrin releasing peptide receptor (GRPR), was similar for targeted and non-targeted formulations. Specificity for GRPR was further established by knocking down GRPR expression with siRNA. Knockdown of the receptor resulted in equivalent intracellular delivery of the FITC with targeted and non-targeted formulations.
Nesbitt, Rae L., "Targeted Intracellular Therapeutic Delivery Using Liposomes Formulated with Multifunctional FAST proteins" (2012). Electronic Thesis and Dissertation Repository. 388.