Evaluation of polymeric nanomedicines targeted to PSMA: effect of ligand on targeting efficiency

Research output: Contribution to journalArticlepeer-review

Authors

  • Adrian V. Fuchs
  • Brian W.C. Tse
  • Mei Chun Yeh
  • Nicholas L. Fletcher
  • Steve S. Huang
  • Warren D. Heston
  • Andrew K. Whittaker
  • Pamela J. Russell
  • Kristofer J. Thurecht

Colleges, School and Institutes

External organisations

  • Queensland University of Technology
  • Cleveland Clinic Foundation
  • ARC Centre of Excellence in Convergent Bio-Nano Science and Technology
  • The University of Queensland

Abstract

Targeted nanomedicines offer a strategy for greatly enhancing accumulation of a therapeutic within a specific tissue in animals. In this study, we report on the comparative targeting efficiency toward prostate-specific membrane antigen (PSMA) of a number of different ligands that are covalently attached by the same chemistry to a polymeric nanocarrier. The targeting ligands included a small molecule (glutamate urea), a peptide ligand, and a monoclonal antibody (J591). A hyperbranched polymer (HBP) was utilized as the nanocarrier and contained a fluorophore for tracking/analysis, whereas the pendant functional chain-ends provided a handle for ligand conjugation. Targeting efficiency of each ligand was assessed in vitro using flow cytometry and confocal microscopy to compare degree of binding and internalization of the HBPs by human prostate cancer (PCa) cell lines with different PSMA expression status (PC3-PIP (PSMA+) and PC3-FLU (PSMA-). The peptide ligand was further investigated in vivo, in which BALB/c nude mice bearing subcutaneous PC3-PIP and PC3-FLU PCa tumors were injected intravenously with the HBP-peptide conjugate and assessed by fluorescence imaging. Enhanced accumulation in the tumor tissue of PC3-PIP compared to PC3-FLU highlighted the applicability of this system as a future imaging and therapeutic delivery vehicle.

Details

Original languageEnglish
Pages (from-to)3235-3247
Number of pages13
JournalBiomacromolecules
Volume16
Issue number10
Early online date3 Sep 2015
Publication statusPublished - 12 Oct 2015