Journal
JOURNAL OF CONTROLLED RELEASE
Volume 136, Issue 1, Pages 14-20Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2009.01.010
Keywords
Polymeric micelle; MRI contrast agent; Long circulation; Tumor imaging; Poly(ethylene glycol)-b-poly(L-lysine)
Funding
- Program for Promoting the Establishment of Strategic Research Centers
- Special Coordination Funds for Promoting Science and Technology
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Tokyo Ohka Foundation for the Promotion of Science and Technology
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A polymeric micelle drug carrier system was applied to the targeting of an MRI (magnetic resonance imaging) contrast agent. A block copolymer, PEG-b-poly(L-lysine), was used for conjugation of gadolinium ions through chelating moieties, DOTA. The DOTA moieties were successfully conjugated to all primary amine groups of the lysine residues. The obtained block copolymer, PEG-b-poly(L-lysine-DOTA), formed a polymeric micelle. The polymeric micelle structure was maintained even after partial gadolinium chelation (similar to 40%) to the DOTA moieties. The prepared polymeric micelle MRI contrast agent was injected into a mouse tail vein at a dose of 0.05 mmol Gd/kg. The polymeric micelle-based MRI contrast agent exhibited stable blood circulation. A considerable amount (6.1 +/- 0.3% of ID/g of the polymeric micelle) was found to accumulate at solid tumors 24 h after intravenous injection by means of the EPR effect. An MRI analysis revealed that the signal intensity of the tumor was enhanced 2.0-fold by the use of this contrast agent. (C) 2009 Elsevier B.V. All rights reserved.
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