Development and in Vivo Quantitative Magnetic Resonance Imaging of Polymer Micelles Targeted to the Melanocortin 1 Receptor

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• 作者：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
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：August 22, 2013
• 年：2013
• 卷：56
• 期：16
• 页码：6330-6338
• 全文大小：416K
• 年卷期：v.56,no.16(August 22, 2013)
• ISSN：1520-4804

文摘

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.