Multifunctional Nanoprobe for MRI/Optical Dual-Modality Imaging and Radical Scavenging

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 C60 derivatives (C60O∼10(OH)∼16(NH2)∼6(NO2)∼6⋅24 H2O) with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) to yield C60O∼10(OH)∼16(NH2)∼6(NO2)∼6⋅24 H2O/(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-prohibited 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.