Development and in vivo quantitative magnetic resonance imaging of polymer micelles targeted to the melanocortin 1 receptor

Natalie M. Barkey, Christian Preihs, Heather H. Cornnell, Gary Martinez, Adam Carie, Josef Vagner, Liping Xu, Mark C. Lloyd, Vincent M. Lynch, Victor J. Hruby, Jonathan L. Sessler, Kevin N. Sill, Robert J. Gillies, David L. Morse

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Recent emphasis has focused on the development of rationally designed polymer-based micelle carriers for drug delivery. The current work tests the hypothesis that target specificity can be enhanced by micelles with cancer-specific ligands. In particular, we describe the synthesis and characterization of a new gadolinium texaphyrin (Gd-Tx) complex encapsulated in an IVECT micellar system, stabilized through Fe(III) cross-linking and targeted with multiple copies of a specific ligand for the melanocortin 1 receptor (MC1R), which has been evaluated as a cell-surface marker for melanoma. On the basis of comparative MRI experiments, we have been able to demonstrate that these Gd-Tx micelles are able to target MC1R-expressing xenograft tumors in vitro and in vivo more effectively than various control systems, including untargeted or un-cross-linked Gd-Tx micelles. Taken in concert, the findings reported herein support the conclusion that appropriately designed micelles are able to deliver contrast agent payloads to tumors expressing the MC1R.

Original languageEnglish (US)
Pages (from-to)6330-6338
Number of pages9
JournalJournal of Medicinal Chemistry
Volume56
Issue number16
DOIs
StatePublished - Aug 22 2013

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Barkey, N. M., Preihs, C., Cornnell, H. H., Martinez, G., Carie, A., Vagner, J., Xu, L., Lloyd, M. C., Lynch, V. M., Hruby, V. J., Sessler, J. L., Sill, K. N., Gillies, R. J., & Morse, D. L. (2013). Development and in vivo quantitative magnetic resonance imaging of polymer micelles targeted to the melanocortin 1 receptor. Journal of Medicinal Chemistry, 56(16), 6330-6338. https://doi.org/10.1021/jm4005576