Targeting prostate cancer cells with hybrid elastin-like polypeptide/liposome nanoparticles

Abstract

Wei Zhang,1 Yunmei Song,1 Preethi Eldi,1 Xiuli Guo,2 John D Hayball,1,3 Sanjay Garg,1 Hugo Albrecht1 1Centre for Pharmaceutical Innovation and Development, Centre for Drug Discovery and Development, Experimental Therapeutics Laboratory, Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia; 2Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan, China; 3Robinson Research Institute and Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia Abstract: Prostate cancer cells frequently overexpress the gastrin-releasing peptide receptor, and various strategies have been applied in preclinical settings to target this receptor for the specific delivery of anticancer compounds. Recently, elastin-like polypeptide (ELP)-based self-assembling micelles with tethered GRP on the surface have been suggested to actively target prostate cancer cells. Poorly soluble chemotherapeutics such as docetaxel (DTX) can be loaded into the hydrophobic cores of ELP micelles, but only limited drug retention times have been achieved. Herein, we report the generation of hybrid ELP/liposome nanoparticles which self-assembled rapidly in response to temperature change, encapsulated DTX at high concentrations with slow release, displayed the GRP ligand on the surface, and specifically bound to GRP receptor expressing PC-3 cells as demonstrated by flow cytometry. This novel type of drug nanocarrier was successfully used to reduce cell viability of prostate cancer cells in vitro through the specific delivery of DTX. Keywords: ELP-GRP, micelle, liposome, docetaxel, prostate cancer, GRPR, GPCR

Keywords

• ELP-GRP
• micelle
• liposome
• docetaxel
• prostate cancer