Gd-DTPA-loaded polymer-metal complex micelles with high relaxivity for MR cancer imaging.

Abstract

Nanodevices for magnetic resonance imaging of cancer were self-assembled to core-shell micellar structures by metal complex formation of K(2)PtCl(6) with diethylenetriaminepentaacetic acid gadolinium (III) dihydrogen (Gd-DTPA), a T(1)-contrast agent, and poly(ethylene glycol)-b-poly{N-[N'-(2-aminoethyl)-2-aminoethyl]aspartamide} (PEG-b-PAsp(DET)) copolymer in aqueous solution. Gd-DTPA-loaded polymeric micelles (Gd-DTPA/m) showed a hydrodynamic diameter of 45 nm and a core size of 22 nm. Confining Gd-DTPA inside the core of the micelles increased the relaxivity of Gd-DTPA more than 13 times (48 mM(-1) s(-1)). In physiological conditions Gd-DTPA/m sustainedly released Gd-DTPA, while the Pt(IV) complexes remain bound to the polymer. Gd-DTPA/m extended the circulation time in plasma and augmented the tumor accumulation of Gd-DTPA leading to successful contrast enhancement of solid tumors. μ-Synchrotron radiation-X-ray fluorescence results confirmed that Gd-DTPA was delivered to the tumor site by the micelles. Our study provides a facile strategy for incorporating contrast agents, dyes and bioactive molecules into nanodevices for developing safe and efficient drug carriers for clinical application.

• Authors: Peng Mi, Horacio Cabral, Daisuke Kokuryo, Mohammad Rafi, Yasuko Terada, Ichio Aoki, Tsuneo Saga, Ishii Takehiko, Nobuhiro Nishiyama, Kazunori Kataoka
• Journal: Biomaterials (Biomaterials) Vol. 34 Issue 2 Pg. 492-500 (Jan 2013) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 23059004 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Contrast Media
• Coordination Complexes
• Drug Carriers
• Micelles
• Proteins
• poly(ethylene glycol)-poly(N'-(N-(2-aminoethyl)-2-aminoethyl)aspartamide) block copolymer
• Polyethylene Glycols
• Gadolinium DTPA

Topics

• Animals
• Cell Line, Tumor
• Contrast Media (administration & dosage, pharmacokinetics)
• Coordination Complexes (chemistry)
• Drug Carriers (chemistry)
• Female
• Gadolinium DTPA (administration & dosage, pharmacokinetics)
• Human Umbilical Vein Endothelial Cells
• Humans
• Magnetic Resonance Imaging
• Mice
• Micelles
• Neoplasms (diagnosis)
• Polyethylene Glycols (chemistry)
• Proteins (chemistry)
• Tissue Distribution