title: Development and in vivo quantitative magnetic resonance imaging of polymer micelles targeted to the melanocortin 1 receptor.
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.
authors.affiliation: Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, United States.
authors.forename: Natalie M
authors.initials: NM
authors.lastname: Barkey
authors.forename: Christian
authors.initials: C
authors.lastname: Preihs
authors.forename: Heather H
authors.initials: HH
authors.lastname: Cornnell
authors.forename: Gary
authors.initials: G
authors.lastname: Martinez
authors.forename: Adam
authors.initials: A
authors.lastname: Carie
authors.forename: Josef
authors.initials: J
authors.lastname: Vagner
authors.forename: Liping
authors.initials: L
authors.lastname: Xu
authors.forename: Mark C
authors.initials: MC
authors.lastname: Lloyd
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Lynch
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Hruby
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Sessler
authors.forename: Kevin N
authors.initials: KN
authors.lastname: Sill
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Gillies
authors.forename: David L
authors.initials: DL
authors.lastname: Morse
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D016513:Mice, SCID; D008823:Micelles; D011108:Polymers / Q000737:chemistry*; D044102:Receptor, Melanocortin, Type 1 / Q000737:chemistry*
chemical_list: D008823:Micelles; D011108:Polymers; D044102:Receptor, Melanocortin, Type 1