Activatable Core–Shell Metallofullerene: An Efficient Nanoplatform for Bimodal Sensing of Glutathione

Abstract

Metallofullerenes have attracted considerable attention as potential novel noninvasive high-relaxivity magnetic resonance contrast agents. However, the applications of metallofullerenes as stimuli-responsive biosensors to monitor biological processes are still scarce. Herein, manganese-fullerenes core–shell nanocomposites are prepared via a facile one-pot approach to achieve GSH-activatable magnetic resonance/fluorescence bimodal imaging functions. The nanocomposites initially have a FRET-induced quenched fluorescence, and water-resisting stimulated low T 1-MRI contrast. Upon exposure to GSH, collapse of the outer MnO2 shell led to reconstruction of the nanoprobes and subsequently resulted in multicolor fluorescence recovery and longitudinal (T 1) relaxivity enhancement (r 1 value up to 29.8 mM–1 s–1 at 0.5 T based on Mn ion). Our work demonstrates feasibility of using fullerenes to fabricate activatable probes for molecular imaging of GSH, which may promote the development of new fullerene-based stimuli-responsive multimodal probes for the detection and regulation of particular biological processes in vivo.

Multifunctional carbon nanomaterials for diagnostic applications in infectious diseases and tumors

“…The non-significantly toxic SL-BGQD ( r 1 = 8.5 mM −1 s −1 ) shows a superior positive contrast than the contrast agent Gd-DTPA ( r 1 = 4.3 mM −1 s −1 ) during imaging and is able to cross the blood-brain barrier to image the neuro vascular system. Peng and coworkers fabricated fullerene quantum dots (FQDs)-MnO 2 nanocomposites responding to GSH levels in tumor cells for glutathione (GSH)-activatable MRI/fluorescence dual-mode imaging [ 144 ]. FQDs not only show an intense PL, but also greatly increase the Mn-based T 1 relaxation rate ( r 1 = 29.8 mM −1 s −1 ).…”

Engineering Intelligent Nanosystems for Enhanced Medical Imaging

“…While many efforts are dedicated to sensing pH and hydrogen peroxide, many more biomedically relevant analytes may be measured, such as levels of ions, [63,[234][235][236][237] reactive oxygen or nitrogen species, [238][239][240][241][242][243][244][245][246] enzymes, [81,[247][248][249][250][251][252][253][254] glutathione, [255][256][257][258][259][260] and other biomarkers. [261][262][263] An example is the ratiometric hypochlorite sensor developed by Zou et al for the detection of arthritis ( Figure 11A).…”

A pH-Activatable MnCO3 Nanoparticle for Improved Magnetic Resonance Imaging of Tumor Malignancy and Metastasis

“…Activatable nanoparticle CAs have been typically designed to further augment the sensitivity and specificity in diagnosis through responding to the abnormal pathological parameters of tumors, such as pH, − redox potential, − and specific enzyme expression. − Among them, manganese-based CAs with remarkable relaxivity and desirable biocompatibility have recently received extensive attention. − For example, manganese oxide (MnO x ) nanomaterials that respond to tumors with subsequent Mn 2+ etching and contrast enhancement have been developed for tumor-specific MRI. − More importantly, the contrast could be further amplified because of the nonspecific binding between the released Mn 2+ and proteins . Although MnO x -based systems have been extensively studied with good results, most MnO x nanomaterials just release Mn 2+ at a relatively low pH (4–6) and sometimes need reductive molecules like glutathione to cooperate, leading to signal activation only in acidic intracellular compartments, such as lysosomes (pH 5–6), rather than tumor microenvironments (pH 6.4–6.8) .…”