期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 56, 期 16, 页码 6330-6338出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm4005576
关键词
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资金
- Bankhead Coley Melanoma Pre-SPORE Program [02-15066-10-03]
- NIH/NCI [R01 CA 097360, CA 68682]
- Intezyne Inc. [84-16301-01-01]
- NATIONAL CANCER INSTITUTE [R01CA068682, P30CA076292, R01CA097360, R01CA125627] Funding Source: NIH RePORTER
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.
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