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

Fuchs, Adrian V., Tse, Brian W.C., Pearce, Amanda. K., Yeh, Mei-Chun, Fletcher, Nicholas L., Huang, Steve S., Heston, Warren D., Whittaker, Andrew K., Russell, Pamela J. and Thurecht, Kristofer J. (2015) Evaluation of polymeric nanomedicines targeted to PSMA: effect of ligand on targeting efficiency. Biomacromolecules, 16 10: 3235-3247. doi:10.1021/acs.biomac.5b00913


Author Fuchs, Adrian V.
Tse, Brian W.C.
Pearce, Amanda. K.
Yeh, Mei-Chun
Fletcher, Nicholas L.
Huang, Steve S.
Heston, Warren D.
Whittaker, Andrew K.
Russell, Pamela J.
Thurecht, Kristofer J.
Title Evaluation of polymeric nanomedicines targeted to PSMA: effect of ligand on targeting efficiency
Journal name Biomacromolecules   Check publisher's open access policy
ISSN 1525-7797
1526-4602
Publication date 2015-10-12
Year available 2015
Sub-type Article (original research)
DOI 10.1021/acs.biomac.5b00913
Open Access Status Not Open Access
Volume 16
Issue 10
Start page 3235
End page 3247
Total pages 13
Place of publication Washington, DC, United States
Publisher American Chemical Society
Collection year 2016
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
Australian Institute for Bioengineering and Nanotechnology Publications
 
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Created: Mon, 07 Sep 2015, 15:39:49 EST by Adrian Fuchs on behalf of Aust Institute for Bioengineering & Nanotechnology