Wu Yufan, Zhao Shuo, Xu Ye, Tang Chaojie, Feng Yujie, Zhang Mianmian, Yang Hong, Ma Yunsheng, Li Yuehua, Wang Wu
Department of Diagnostic and Interventional Radiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, P. R. China.
Joint International Research Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, and Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai 200234, P. R. China.
ACS Appl Nano Mater. 2024 Apr 4;7(8):9020-9030. doi: 10.1021/acsanm.4c00511. eCollection 2024 Apr 26.
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 CA, Gd-ZnDPA nanoprobe, which consists of a hexanuclear gadolinium nanocluster (Gd) with an apoptosis-targeting group (ZnDPA). The amplification of Gd(III) by the hexanuclear structure generates its high longitudinal relaxivity (44.67 mM s, 1T) and low / ratio (0.68, 1T). Based on the Solomon-Bloembergen-Morgan (SBM) theory, this notable improvement is primarily ascribed to a long correlation tumbling time (τ). More importantly, the Gd-ZnDPA nanoprobe shows excellent tumor apoptosis properties with an enhanced MR signal ratio (∼74%) and a long MRI imaging acquisition time window (∼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.
磁共振成像（MRI）有助于对接受化疗的患者的肿瘤组织进行无创评估，从而产生对肿瘤预后和治疗策略制定至关重要的基本诊断数据。目前，市售的MRI造影剂（CAs）主要由单核钆（III）配合物组成。由于每个分子中只有一个Gd（III）原子，这些造影剂通常需要高剂量给药才能达到所需的造影质量，这不可避免地会导致一些不良事件。在此，我们开发了一种六核、靶向凋亡的造影剂Gd-ZnDPA纳米探针，它由具有靶向凋亡基团（ZnDPA）的六核钆纳米簇（Gd）组成。六核结构对Gd（III）的放大作用使其具有高纵向弛豫率（44.67 mM-1 s-1，1T）和低r2/r1比值（0.68，1T）。基于所罗门-布洛姆贝根-摩根（SBM）理论，这种显著的改善主要归因于长相关翻滚时间（τc）。更重要的是，Gd-ZnDPA纳米探针在4T1荷瘤小鼠中表现出优异的肿瘤凋亡特性，具有增强的MR信号比值（约74%）和较长的MRI成像采集时间窗（约48小时）。本研究引入了一种基于钆的实验性造影剂，用于在MRI背景下对肿瘤凋亡进行潜在成像。
