Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 19, Issue 43, Pages 14675-14681Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201301601
Keywords
fluorescence; fullerenes; imaging agents; magnetic resonance imaging; radical scavengers
Categories
Funding
- 973 Program [2011CB302100]
- National Natural Science Foundation of China [21121063, 51072200, 31170963]
- NSAF [11076027]
- EU [263147]
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The development of novel nanomaterials for the diagnosis and/or treatment of human diseases has become an important issue. In this work, a multifunctional theranostic agent was designed by covalently binding hydroxyl-and amino-bearing C-60 derivatives (C60O-10(OH)(-16)(NH2)(-6)-(NO2)(-6)center dot 24H(2)O) with gadolinium diethylenetriaminepentaacetic acid (GdDTPA) to yield C60O-10(OH)(-16)(NH2)similar to (6)(NO2)-6 center dot 24H(2)O/(Gd-DTPA)(3) (DF1Gd3). The obtained DF1Gd3 shows more than fourfold contrast improvement over commercial Gd-DTPA along with multiwavelength fluorescent emission for dual-modality diagnosis. An inner-ear magnetic resonance imaging (MRI) study was designed as a model of biological barriers, including the blood/brain barrier (BBB) for DF1Gd3 to investigate its in vivo behavior. This revealed that the fabricated contrast agent dramatically increases the local contrast but can not cross the middle ear/inner ear barrier and endolymph/perilymph barrier in the inner ear, and thus it is also BBB-pro-hibited in normal individuals. In vivo biodistribution studies suggested that 1) DF1Gd3 could circulate in vessels for a relatively long time and is mainly eliminated through liver and kidney, 2) DF1Gd3 may potentially function as a liver-specific MRI contrast agent. Interestingly, DF1Gd3 also shows an excellent quenching effect on hydroxyl radicals, as revealed by the DMPO spin trap/ESR method. The combination of enhanced MRI/FL imaging and local treatment of lesions is unique to DF1Gd3 and potentiates the medical paradigm of detect and treat/prevent in combating human diseases related to reactive oxygen.
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