A Hexanuclear Gadolinium(III)-Based Nanoprobe for Magnetic Resonance Imaging of Tumor Apoptosis

Magnetic resonance imaging (MRI) is instrumental in the noninvasive evaluation of tumor tissues in patients subjected to chemotherapy, thereby yielding essential diagnostic data crucial for the prognosis of tumors and the formulation of therapeutic strategies. Currently, commercially available MRI contrast agents (CAs) predominantly consist of mononuclear gadolinium(III) complexes. Because there is only one Gd(III) atom per molecule, these CAs often require administration in high doses to achieve the desired contrast quality, which inevitably leads to some adverse events. Herein, we develop a six-nuclei, apoptosis-targeting T-1 CA, Gd-6-ZnDPA nanoprobe, which consists of a hexanuclear gadolinium nanocluster (Gd-6) with an apoptosis-targeting group (ZnDPA). The amplification of Gd(III) by the hexanuclear structure generates its high longitudinal relaxivity (44.67 mM(-1) s(-1), 1T) and low r(1)/r(2) ratio (0.68, 1T). Based on the Solomon-Bloembergen-Morgan (SBM) theory, this notable improvement is primarily ascribed to a long correlation tumbling time (tau(R)). More importantly, the Gd-6-ZnDPA nanoprobe shows excellent tumor apoptosis properties with an enhanced MR signal ratio (similar to 74%) and a long MRI imaging acquisition time window (similar to 48 h) in 4T1 tumor-bearing mice. This study introduces an experimental gadolinium-based CA for the potential imaging of tumor apoptosis in the context of MRI.