title: Targeting Nanomedicines to Prostate Cancer: Evaluation of Specificity of Ligands to Two Different Receptors In Vivo.
abstract: This manuscript utilised in vivo multispectral imaging to demonstrate the efficacy of two different nanomedicine formulations for targeting prostate cancer.
  
  
  
  Pegylated hyperbranched polymers were labelled with fluorescent markers and targeting ligands against two different prostate cancer markers; prostate specific membrane antigen (PSMA) and the protein kinase, EphrinA2 receptor (EphA2). The PSMA targeted nanomedicine utilised a small molecule glutamate urea inhibitor of the protein, while the EphA2 targeted nanomedicine was conjugated to a single-chain variable fragment based on the antibody 4B3 that has shown high affinity to the receptor.
  
  
  
  Hyperbranched polymers were synthesised bearing the different targeting ligands. In the case of the EphA2-targeting nanomedicine, significant in vitro uptake was observed in PC3 prostate cancer cells that overexpress the receptor, while low uptake was observed in LNCaP cells (that have minimal expression of this receptor). Conversely, the PSMA-targeted nanomedicine showed high uptake in LNCaP cells, with only minor uptake in the PC3 cells. In a dual-tumour xenograft mouse model, the nanomedicines showed high uptake in tumours in which the receptor was overexpressed, with only minimal non-specific accumulation in the low-expression tumours.
  
  
  
  This work highlighted the importance of clearly defining the target of interest in next-generation nanomedicines, and suggests that dual-targeting in such nanomedicines may be a means to achieve greater efficacy.
authors.affiliation: Centre for Advanced Imaging, Australian Institute for Bioengineering and Nanotechnology and the ARC Centre of Excellence in Convergent BioNano Science and Technology, The University of Queensland, Building 57, St Lucia, QLD, 4072, Australia.
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Pearce
authors.affiliation: Centre for Advanced Imaging, Australian Institute for Bioengineering and Nanotechnology and the ARC Centre of Excellence in Convergent BioNano Science and Technology, The University of Queensland, Building 57, St Lucia, QLD, 4072, Australia.
authors.forename: Adrian V
authors.initials: AV
authors.lastname: Fuchs
authors.affiliation: Centre for Advanced Imaging, Australian Institute for Bioengineering and Nanotechnology and the ARC Centre of Excellence in Convergent BioNano Science and Technology, The University of Queensland, Building 57, St Lucia, QLD, 4072, Australia.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Fletcher
authors.affiliation: Centre for Advanced Imaging, Australian Institute for Bioengineering and Nanotechnology and the ARC Centre of Excellence in Convergent BioNano Science and Technology, The University of Queensland, Building 57, St Lucia, QLD, 4072, Australia. k.thurecht@uq.edu.au.
authors.forename: Kristofer J
authors.initials: KJ
authors.lastname: Thurecht
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods* / Q000592:standards; D004353:Drug Evaluation, Preclinical / Q000379:methods; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008297:Male; D050997:Nanomedicine / Q000379:methods* / Q000592:standards; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D036104:Receptor, EphA2 / Q000378:metabolism*
chemical_list: D000954:Antigens, Surface; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D008024:Ligands; D036104:Receptor, EphA2; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II
keywords: antibody; fluorescence imaging; molecular imaging; nanomedicine; nanotherapeutics