title: Targeting prostate cancer cells with genetically engineered polypeptide-based micelles displaying gastrin-releasing peptide.
abstract: 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.
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Garg
authors.affiliation: 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.
authors.forename: Preethi
authors.initials: P
authors.lastname: Eldi
authors.affiliation: SAHMRI, North Terrace, Adelaide, SA 5001, Australia.
authors.forename: Fiona Huan-Huan
authors.initials: FH
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Ian R D
authors.initials: IR
authors.lastname: Johnson
authors.affiliation: 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.
authors.forename: Doug A
authors.initials: DA
authors.lastname: Brooks
authors.affiliation: 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.
authors.forename: Frankie
authors.initials: F
authors.lastname: Lam
authors.affiliation: SAHMRI, North Terrace, Adelaide, SA 5001, Australia.
authors.forename: Grigori
authors.initials: G
authors.lastname: Rychkov
authors.affiliation: 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.
authors.forename: John
authors.initials: J
authors.lastname: Hayball
authors.affiliation: 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: hugo.albrecht@unisa.edu.au.
authors.forename: Hugo
authors.initials: H
authors.lastname: Albrecht
mesh_terms: D000817:Anilino Naphthalenesulfonates / Q000737:chemistry; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D004549:Elastin; D004705:Endocytosis; D005456:Fluorescent Dyes / Q000737:chemistry; D019886:Gastrin-Releasing Peptide / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D005818:Genetic Engineering; D006801:Humans; D008297:Male; D008823:Micelles; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D011471:Prostatic Neoplasms / Q000378:metabolism; D018004:Receptors, Bombesin / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000817:Anilino Naphthalenesulfonates; D004337:Drug Carriers; D005456:Fluorescent Dyes; D008823:Micelles; D010455:Peptides; D018004:Receptors, Bombesin; D011993:Recombinant Fusion Proteins; C027132:1-anilino-8-naphthalenesulfonate; D019886:Gastrin-Releasing Peptide; D004549:Elastin
keywords: Elastin-like polypeptide (ELP); G protein-coupled receptors (GPCRs); Gastrin releasing peptide (GRP); Micelle; Prostate cancer