Pharmaceutical Liposomes Targeted to PC3 Prostate Carcinoma Cells by Fusion Phage Proteins
P.K. Jayanna, T. Wang, D. Bedi, P. Deinnocentes, R.C. Bird, V.P. Torchilin, V.A. Petrenko
Auburn University, US
Keywords: targeted liposomes, phage fusion protein, phage liposomes
Abstract:Peptide phage display offers a convenient high-throughput approach to screen for tumor-selective probes. Earlier research in our laboratory has been successful in isolating phage peptides selective and specific for PC3 prostate cancer cells. Furthermore we have demonstrated the proof of concept data for a technique of inserting the tumor-specific peptides into liposomes exploiting the intrinsic physico-chemical properties of the phage coat protein. Here we describe the production of labeled liposomes targeted to PC3 prostate tumor cells. The targeting was demonstrated using fluorescence microscopy as well as FACS. Furthermore, we describe the modification of commercial DOXIL utilizing the above technique with PC3-specific phage peptides so as to obtain targeted DOXIL. The targeted liposomes were shown to exert a higher cytotoxic effect against PC3 cells compared to the non-targeted DOXIL in vitro indicating a possible therapeutic advantage. The simplicity of the approach to produce targeted liposomes coupled with the ability to rapidly obtain tumor-specific phage fusion proteins via phage display allows one to envisage a combinatorial system for the production of targeted liposomal therapeutics.