Evaluation of Polymeric Nanomedicines Targeted to PSMA: Effect of Ligand on Targeting Efficiency

Biomacromolecules
Adrian V FuchsKristofer J Thurecht

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 PC...Continue Reading

References

Jul 21, 2001·Journal of Medicinal Chemistry·A P KozikowskiJ T Wroblewski
Dec 12, 2002·Urologic Oncology·Sam S Chang, Warren D W Heston
Oct 7, 2003·Molecular Biology of the Cell·Sigrid A RajasekaranAyyappan K Rajasekaran
Feb 3, 2004·Journal of Cellular Biochemistry·Arundhati Ghosh, Warren D W Heston
Apr 20, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Neil H BanderStanley J Goldsmith
Nov 6, 2009·Journal of the American Chemical Society·Ryan P MurelliDavid A Spiegel
Mar 30, 2010·Journal of the American Chemical Society·Kristofer J ThurechtAndrew K Whittaker
Feb 8, 2011·CA: a Cancer Journal for Clinicians·Ahmedin JemalDavid Forman
Oct 8, 2011·International Journal of Nanomedicine·Xin WuShen Gao
Aug 8, 2012·ACS Nano·Zhihang ChenZaver M Bhujwalla
Feb 19, 2013·Chemical Communications : Chem Comm·Daniel J ColesKristofer J Thurecht
Feb 19, 2014·Journal of Medicinal Chemistry·Sangeeta Ray BanerjeeMartin G Pomper
Sep 23, 2014·Molecular Cancer Therapeutics·Xinning WangJames P Basilion
Nov 20, 2014·Nanomedicine·Brian Wan-Chi TsePamela J Russell
Nov 21, 2014·European Journal of Nuclear Medicine and Molecular Imaging·Ali Afshar-OromiehUwe Haberkorn
Mar 21, 2015·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Matthias EiberMarkus Schwaiger

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Citations

Jun 11, 2016·Advanced Healthcare Materials·Christopher B HowardKristofer J Thurecht
Jun 23, 2016·European Journal of Nuclear Medicine and Molecular Imaging·Stefano BoschiKen Herrmann
Feb 28, 2018·Nanomedicine·Anna Cifuentes-RiusNicolas H Voelcker
Aug 23, 2019·Current Drug Delivery·Pritish Kumar PandaSanjay K Jain
Sep 30, 2017·Advanced Healthcare Materials·Amal J SivaramKristofer J Thurecht
Sep 17, 2020·Macromolecular Rapid Communications·Amal J SivaramKristofer J Thurecht
Aug 4, 2016·Molecular Cancer Therapeutics·Amarnath MukherjeeShawn E Lupold
Dec 18, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Maja SevericWafa T Al-Jamal
Feb 15, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Alireza KavandDelphine Chan-Seng
Apr 12, 2021·Carbohydrate Polymers·Anitha ALisbeth Grøndahl
Sep 20, 2017·ACS Nano·Mattias BjörnmalmFrank Caruso
Jul 23, 2020·Current Pharmaceutical Design·Hooman YariVibhudutta Awasthi
Dec 17, 2019·Molecular Pharmaceutics·Sudath HapuarachchigeDmitri Artemov
Dec 17, 2016·Organic Letters·Mathilde VandammeJean-François Paquin

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