Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST , Campus UAB, Bellaterra , 08193 Barcelona , Spain.
Departament de Bioquímica i Biologia Molecular , Universitat Autònoma de Barcelona , 08193 Cerdanyola del Vallès , Spain.
ACS Appl Mater Interfaces. 2018 Nov 14;10(45):38819-38832. doi: 10.1021/acsami.8b15594. Epub 2018 Nov 1.
In the last years, extensive attention has been paid on designing and developing functional imaging contrast agents for providing accurate noninvasive evaluation of pathology in vivo. However, the issue of false-positives or ambiguous imaging and the lack of a robust strategy for simultaneous dual-mode imaging remain to be fully addressed. One effective strategy for improving it is to rationally design magnetic resonance imaging (MRI) contrast agents (CAs) with intrinsic T/ T dual-mode imaging features. In this work, the development and characterization of one-pot synthesized nanostructured coordination polymers (NCPs) which exhibit dual mode T/ T MRI contrast behavior is described. The resulting material comprises the combination of different paramagnetic ions (Fe, Gd, Mn) with selected organic ligands able to induce the polymerization process and nanostructure stabilization. Among them, the Fe-based NCPs showed the best features in terms of colloidal stability, low toxicity, and dual T/ T MRI contrast performance overcoming the main drawbacks of reported CAs. The dual-mode CA capability was evaluated by different means: in vitro phantoms, ex vivo and in vivo MRI, using a preclinical model of murine glioblastoma. Interestingly, the in vivo MRI of Fe-NCPs show T and T high contrast potential, allowing simultaneous recording of positive and negative contrast images in a very short period of time while being safer for the mouse. Moreover, the biodistribution assays reveals the persistence of the nanoparticles in the tumor and subsequent gradual clearance denoting their biodegradability. After a comparative study with commercial CAs, the results suggest these nanoplatforms as promising candidates for the development of dual-mode MRI CAs with clear advantages.
在过去的几年中,人们广泛关注设计和开发功能成像对比剂,以提供对体内病理学的准确无创评估。然而,假阳性或成像模糊的问题以及缺乏同时进行双模式成像的稳健策略仍然需要得到充分解决。一种有效的改进策略是合理设计具有内在 T1/T2 双模式成像特性的磁共振成像(MRI)对比剂(CA)。在这项工作中,描述了一锅合成的纳米结构配位聚合物(NCP)的开发和表征,其表现出双模式 T1/T2 MRI 对比行为。所得材料包括不同顺磁离子(Fe、Gd、Mn)与能够诱导聚合过程和纳米结构稳定的选定有机配体的组合。其中,基于 Fe 的 NCP 在胶体稳定性、低毒性和双 T1/T2 MRI 对比性能方面表现出最佳特性,克服了报道的 CA 的主要缺点。通过不同的方法评估了双模式 CA 的能力:体外体模、离体和体内 MRI,使用小鼠脑胶质瘤的临床前模型。有趣的是,Fe-NCPs 的体内 MRI 显示出 T1 和 T2 高对比潜力,允许在非常短的时间内同时记录正性和负性对比图像,同时对小鼠更安全。此外,生物分布测定揭示了纳米粒子在肿瘤中的持久性和随后的逐渐清除,表明它们具有生物降解性。与商业 CA 进行比较研究后,结果表明这些纳米平台是开发具有明显优势的双模式 MRI CA 的有前途的候选物。