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., & Thurecht, Kristofer J. (2015) Evaluation of polymeric nanomedicines targeted to PSMA: Effect of ligand on targeting efficiency. Biomacromolecules, 16(10), pp. 3235-3247.

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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.

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6 citations in Web of Science®

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ID Code: 94652
Item Type: Journal Article
Refereed: Yes
Keywords: targeted nanomedicines, prostate cancer, prostate-specific membrane antigen (PSMA), polymeric nanomedicines, ligands, flourophore, flourescence imaging, tracking/analysis, cancer imaging, therapeutic delivery vehicle, hyperbranched polymer
DOI: 10.1021/acs.biomac.5b00913
ISSN: 1526-4602
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Cell Biology (111201)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Diagnosis (111202)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Therapy (excl. Chemotherapy and Radiation Therapy) (111204)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Molecular Targets (111207)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Funding:
Copyright Owner: Copyright 2015 American Chemical Society
Deposited On: 08 Apr 2016 03:15
Last Modified: 25 May 2016 23:02

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