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Abstract:
Gadolinium-based contrast agents for imaging of cellular or subcellular compartments by clinical magnetic resonance imaging (MRI) currently lack a satisfying signal-to-noise ratio and acceptable target specificity. Water-soluble enzyme nanoreactors based on amphiphilic triblock copolymer membranes functionalized with size-selective pore proteins were used to precipitate highly insoluble gadolinium phosphate nanoparticles inside the vesicles. Surface modification with the macrophage scavenger receptor A1 (SRA-1) ligand polyguanylic acid and fluorescence-labeled streptavidin resulted in a novel type of bimodal target-specific contrast agent for MR and fluorescence imaging. Physicochemical analyses showed vesicles with a mean diameter of 46 +/- 9 nm and distinguishable particulate content with high electron density. In MRI, the nanocarrier displayed a T1 relaxivity of 3.5e10 L x s(-1) x mmol(-1) vesicles. Uptake to target cells and intracellular localization was proven both with confocal microscopy and MRI. In conclusion, we introduce a novel receptor-targetable gadolinium nanoparticle-based vesicular contrast agent for bimodal imaging in clinical medicine and show its use in first in vitro and cell culture experiments.