Hybrid Nanomaterials as Multimodal Imaging Contrast Agents
First Claim
1. A contrast agent for magnetic resonance imaging (MRI) comprising a hybrid nanoparticle, said hybrid nanoparticle comprising:
- a polymeric matrix material; and
a plurality of coordination complexes, each coordination complex comprising a functionalized chelating group and a paramagnetic metal ion.
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Abstract
The presently disclosed subject matter provides hybrid nanomaterials for use as magnetic resonance imaging (MRI), optical and/or multimodal contrast imaging agents. The hybrid nanomaterials comprise a polymeric matrix material and a plurality of coordination complexes, each coordination complex comprising a functionalized chelating group and a paramagnetic metal ion. The nanoparticle can further comprise a luminophore. Methods of synthesizing and using the nanoparticles are provided. The nanoparticles can be used to diagnose diseases, including cancer, cardiovascular disease, and diseases related to inflammation.
45 Citations
100 Claims
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1. A contrast agent for magnetic resonance imaging (MRI) comprising a hybrid nanoparticle, said hybrid nanoparticle comprising:
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a polymeric matrix material; and a plurality of coordination complexes, each coordination complex comprising a functionalized chelating group and a paramagnetic metal ion. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56)
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57. A formulation comprising:
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a hybrid nanoparticle, wherein the hybrid nanoparticle comprises a polymeric matrix material and a plurality of coordination complexes, each coordination complex comprising a functionalized chelating group and a paramagnetic metal ion; and a pharmaceutically acceptable carrier. - View Dependent Claims (58, 59)
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60. A method of imaging one of a cell, a tissue, and a subject, the method comprising:
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administering to one of a cell, a tissue, and a subject a contrast agent, said contrast agent comprising a hybrid nanoparticle, said hybrid nanoparticle comprising; a polymeric matrix material; and a plurality of coordination complexes, each coordination complex comprising a functionalized chelating group and a paramagnetic metal ion; and rendering a magnetic resonance image of the one of a cell, a tissue, and a subject. - View Dependent Claims (61, 62)
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63. A method of detecting a disease state in one of a cell, a tissue, and a subject, said method comprising:
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administering to one of a cell, a tissue, and a subject a contrast agent, said contrast agent comprising a hybrid nanoparticle, said hybrid nanoparticle comprising; a polymeric matrix material; and a plurality of coordination complexes, each coordination complex comprising a functionalized chelating group and a paramagnetic metal ion; and rendering a magnetic resonance image of the one of a cell, a tissue and a subject, thereby detecting a disease state in the one of a cell, a tissue and a subject. - View Dependent Claims (64, 65, 66)
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67. A method of synthesizing a hybrid nanoparticle, said hybrid nanoparticle comprising a polymeric matrix material and a plurality of coordination complexes, each of the plurality of coordination complexes comprising a functionalized chelating group and a paramagnetic metal ion, the method comprising:
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(a) providing a first mixture comprising a water-in-oil microemulsion system comprising water, an organic solvent, a surfactant, and a co-surfactant; (b) adding a polymerizable monomer and a plurality of coordination complexes, each of said plurality of coordination complexes comprising a functionalized chelating group and a paramagnetic metal ion, to the first mixture to form a second mixture; (c) mixing said second mixture for a first period of time; (d) adding a polymerization agent to the second mixture to form a third mixture; and (e) mixing the third mixture for a second period of time to form a hybrid nanoparticle. - View Dependent Claims (68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91)
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92. A method of synthesizing a hybrid nanoparticle, said hybrid nanoparticle comprising a polymeric matrix material and a plurality of coordination complexes, each of the plurality of coordination complexes comprising a functionalized chelating group and a paramagnetic metal ion, further wherein one or more of the plurality of coordination complexes is bound to a surface of the hybrid nanoparticle, the method comprising:
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(a) providing a first mixture comprising a water-in-oil microemulsion system comprising water, an organic solvent, a surfactant and a co-surfactant; (b) adding a polymerizable monomer to the first mixture to form a second mixture; (c) mixing said second mixture for a first period of time; (d) adding a polymerization agent to the second mixture to form a third mixture; (e) mixing the third mixture for a second period of time; (f) adding to the third mixture a plurality of coordination complexes, each of the plurality of coordination complexes comprising a functionalized chelating group and a paramagnetic metal ion to form a fourth mixture; and (g) mixing the fourth mixture for a third period of time to form a hybrid nanoparticle having one or more of the plurality of coordination complexes bound to a surface of the hybrid nanoparticle. - View Dependent Claims (93, 94, 95)
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96. A method of synthesizing a layered hybrid nanoparticle, said layered hybrid nanoparticle comprising a polymeric matrix material and a plurality of coordination complexes, each of the plurality of coordination complexes comprising a functionalized chelating group and a paramagnetic metal ion, the method comprising:
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(a) preparing a hybrid nanoparticle in a water-in-oil microemulsion, said hybrid nanoparticle comprising a polymeric matrix material and a plurality of coordination complexes, each of the plurality of coordination complexes comprising a functionalized chelating group and a paramagnetic metal ion; and (b) adsorbing onto the hybrid nanoparticle prepared in step (a) a polymer comprising additional coordination complexes, said additional coordination complexes each comprising a functionalized chelating group and a paramagnetic metal ion to form a layer of polymerized coordination complexes over the surface of the hybrid nanoparticle. - View Dependent Claims (97, 98, 99, 100)
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Specification