Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
Department of Radiology, Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
ACS Appl Mater Interfaces. 2020 Jun 3;12(22):24644-24654. doi: 10.1021/acsami.0c07018. Epub 2020 May 21.
Recently, Mn(II)-based T-weighted magnetic resonance imaging (MRI) contrast agents (CAs) have been explored widely for cancer diagnosis. However, the "always-on" properties and poor excretability of the conventional Mn(II)-based CAs leads to high background signals and unsatisfactory clearance from the body. Here, we report an " three-dimensional to two-dimensional (3D-to-2D) transformation" method to prepare novel excretable 2D manganese-based layered silicates (Mn-LSNs) with extremely high signal-to-noise for tumor-specific MR imaging for the first time. Our observations combined with density functional theory (DFT) calculations reveal that 3D metal (Mn, Fe, Co) oxide nanoparticles are initially formed from the molecular precursor solution and then transform into 2D metal (Mn, Fe, Co)-based layered silicates triggered by the addition of tetraethyl orthosilicate, which provides a time-saving and versatile way to prepare novel 2D silicate nanomaterials. The unique ion-exchangeable capacity and high host layer charge density endow Mn-LSNs with an "ON/OFF" pH/GSH stimuli-activatable T relaxivity with superb high signal-to-noise (640-, 1200-fold for slightly acidic and reductive changes, respectively). Further MR imaging reveals that Mn-LSNs exhibit a continuously rapid T-MRI signal enhancement in tumor tissue and no visible signal enhancement in normal tissue, indicating an excellent tumor-specific imaging. In addition, Mn-LSNs exhibit a rapid excretion from the mouse body in 24 h and invisible organ toxicity, which could help to solve the critical intractable degradation issue of conventional inorganic CAs. Moreover, the tumor microenvironment (pH/GSH/HO) specific degradability of Mn-LSNs could help to improve the penetration depth of particles into the tumor parenchyma. Developing this novel Mn-LSNs contrast agent, together with the already demonstrated capacity of layered silicates for drug and gene delivery, provides opportunities for future cancer theranostics.
最近，基于 Mn(II)的 T 加权磁共振成像 (MRI) 对比剂 (CAs) 已被广泛用于癌症诊断。然而，传统基于 Mn(II)的 CAs 的“常开”特性和较差的排泄能力导致背景信号高，并且难以从体内清除。在这里，我们首次报道了一种“从三维到二维 (3D-to-2D) 转变”的方法来制备新型可排泄的二维锰基层状硅酸盐 (Mn-LSNs)，其具有极高的肿瘤特异性 MRI 信号。我们的观察结果结合密度泛函理论 (DFT) 计算表明，3D 金属 (Mn、Fe、Co) 氧化物纳米颗粒最初是由分子前体溶液形成的，然后在添加正硅酸乙酯的触发下转化为 2D 金属 (Mn、Fe、Co) 基层状硅酸盐，这为制备新型 2D 硅酸盐纳米材料提供了一种节省时间和通用的方法。独特的离子交换能力和高主层电荷密度使 Mn-LSNs 具有“ON/OFF”pH/GSH 刺激激活的 T 弛豫率，具有出色的高信噪比 (分别为轻微酸性和还原变化时的 640 倍和 1200 倍)。进一步的 MRI 成像表明，Mn-LSNs 在肿瘤组织中表现出连续快速的 T-MRI 信号增强，而在正常组织中没有可见的信号增强，表明具有优异的肿瘤特异性成像。此外，Mn-LSNs 在 24 小时内从小鼠体内迅速排出，并且没有可见的器官毒性，这有助于解决传统无机 CAs 难以降解的关键问题。此外，Mn-LSNs 的肿瘤微环境 (pH/GSH/HO) 特异性降解能力有助于提高颗粒进入肿瘤实质的穿透深度。开发这种新型 Mn-LSNs 对比剂，结合层状硅酸盐在药物和基因传递方面的已有能力，为未来的癌症治疗提供了机会。
