Targeting nanomedicines to prostate cancer: evaluation of specificity of ligands to two different receptors in vivo

Research output: Contribution to journalArticlepeer-review

Authors

Colleges, School and Institutes

External organisations

  • The University of Queensland

Abstract

Purpose: This manuscript utilised in vivo multispectral imaging to demonstrate the efficacy of two different nanomedicine formulations for targeting prostate cancer.

Methods: 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.

Results: 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.

Conclusions: 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.

Details

Original languageEnglish
Pages (from-to)2388-2399
Number of pages12
JournalPharmaceutical Research
Volume33
Issue number10
Early online date25 May 2016
Publication statusPublished - Oct 2016

Keywords

  • antibody, fluorescence imaging, molecular imaging, nanomedicine, nanotherapeutics

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