In recent years G protein-coupled receptors (GPCRs) have emerged as crucial tumorigenic factors that drive aberrant cancer growth, metastasis and angiogenesis. Consequently, a number of GPCRs are strongly expressed in cancer derived cell lines and tissue samples. Therefore a rational anti-cancer strategy is the design of nano-medicines that specifically target GPCRs to bind and internalise cytotoxic drugs into cancer cells. Herein, we report the genetic engineering of a self-assembling nanoparticle based on elastin-like polypeptide (ELP), which has been fused with gastrin releasing peptide (GRP). These nanoparticles increased intracellular calcium concentrations when added to GRP receptor positive PC-3 prostate cancer cells, demonstrating specific receptor activation. Moreover, GRP-displaying fluorescent labelled nanoparticles showed specific cell-surface interaction with PC-3 prostate cancer cells and increased endocytic uptake. These nanoparticles therefore provide a targeted molecular carrier system for evaluating the delivery of cytotoxic drugs into cancer cells.
International journal of pharmaceutics. 2016 Sep 12 [Epub ahead of print]
Wei Zhang, Sanjay Garg, Preethi Eldi, Fiona Huan-Huan Zhou, Ian R D Johnson, Doug A Brooks, Frankie Lam, Grigori Rychkov, John Hayball, Hugo Albrecht
Centre for Pharmaceutical Innovation and Development, Centre for Drug Discovery and Development, Sansom Institute for Health Research, and School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5001, Australia., SAHMRI, North Terrace, Adelaide, SA 5001, Australia., Centre for Pharmaceutical Innovation and Development, Centre for Drug Discovery and Development, Sansom Institute for Health Research, and School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5001, Australia. Electronic address: .