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

J Med Chem. 2013 Aug 22;56(16):6330-8. doi: 10.1021/jm4005576. Epub 2013 Aug 9.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Mice, SCID
  • Micelles*
  • Polymers / chemistry*
  • Receptor, Melanocortin, Type 1 / chemistry*

Substances

  • Micelles
  • Polymers
  • Receptor, Melanocortin, Type 1