Gd-DTPA-loaded polymer-metal complex micelles with high relaxivity for MR cancer imaging.
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.
Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
Peng
P
Mi
Horacio
H
Cabral
Daisuke
D
Kokuryo
Mohammad
M
Rafi
Yasuko
Y
Terada
Ichio
I
Aoki
Tsuneo
T
Saga
Ishii
I
Takehiko
Nobuhiro
N
Nishiyama
Kazunori
K
Kataoka
D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000008:administration & dosage* / Q000493:pharmacokinetics; D056831:Coordination Complexes / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D019786:Gadolinium DTPA / Q000008:administration & dosage* / Q000493:pharmacokinetics; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008823:Micelles; D009369:Neoplasms / Q000175:diagnosis*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D014018:Tissue Distribution
D003287:Contrast Media; D056831:Coordination Complexes; D004337:Drug Carriers; D008823:Micelles; D011506:Proteins; C571441:poly(ethylene glycol)-poly(N'-(N-(2-aminoethyl)-2-aminoethyl)aspartamide) block copolymer; D011092:Polyethylene Glycols; D019786:Gadolinium DTPA