Haedicke Inga E, Li Tan, Zhu Yong Le K, Martinez Francisco, Hamilton Amanda M, Murrell Donna H, Nofiele Joris T, Cheng Hai-Ling M, Scholl Timothy J, Foster Paula J, Zhang Xiao-An
Department of Chemistry , University of Toronto , Toronto , ON M5S 3H6 , Canada . Email:
Department of Physical and Environmental Sciences , University of Toronto Scarborough , 1265 Military Trail , Toronto , ON M1C 1A4 , Canada.
Chem Sci. 2016 Jul 1;7(7):4308-4317. doi: 10.1039/c5sc04252f. Epub 2016 Mar 16.
Magnetic resonance imaging (MRI) is a preferred technique for noninvasively monitoring the fate of implanted cells, such as stem cells and immune cells . Cellular MRI requires contrast agents (CAs) to label the cells of interest. Despite promising progress made in this emerging field, highly sensitive, stable and biocompatible CAs with high cell permeability and specificity remains an unmet challenge. To address this need, a novel Mn-porphyrin, MnAMP was designed and synthesized based on the modification of Mntetra(carboxy-porphyrin) (MnTCP), a small and highly stable non-Gd extracellular CA with good biocompatibility and high relaxivity ( = 7.9 mM s) at clinical field of 3 Tesla (T). Cell permeability was achieved by masking the polar carboxylates of MnTCP with acetoxymethyl-ester (AM) groups, which are susceptible to hydrolysis by intracellular esterases. The enzymatic cleavage of AM groups led to disaggregation of the hydrophobic MnAMP, releasing activated MnTCP with significant increase in relaxivity. Cell uptake of MnAMP is highly efficient as tested on two non-phagocytic human cell lines with no side effects observed on cell viability. MRI of labeled cells exhibited significant contrast enhancement with a short of 161 ms at 3 T, even though a relatively low concentration of MnAMP and short incubation time was applied for cell labeling. Overall, MnAMP is among the most efficient cell labeling agents developed for cellular MRI.
磁共振成像（MRI）是一种用于无创监测植入细胞（如干细胞和免疫细胞）命运的首选技术。细胞MRI需要造影剂（CAs）来标记感兴趣的细胞。尽管在这个新兴领域取得了令人鼓舞的进展，但具有高细胞渗透性和特异性的高灵敏度、稳定且生物相容的CAs仍然是一个未解决的挑战。为了满足这一需求，基于锰四（羧基卟啉）（MnTCP）的修饰设计并合成了一种新型锰卟啉MnAMP，MnTCP是一种小的、高度稳定的非钆细胞外造影剂，在3特斯拉（T）的临床场强下具有良好的生物相容性和高弛豫率（ = 7.9 mM s）。通过用乙酰氧基甲基酯（AM）基团掩盖MnTCP的极性羧酸盐来实现细胞渗透性，AM基团易被细胞内酯酶水解。AM基团的酶促裂解导致疏水性MnAMP解聚，释放出活化的MnTCP，弛豫率显著增加。在两种非吞噬性人类细胞系上测试发现，MnAMP的细胞摄取效率很高，且未观察到对细胞活力有副作用。标记细胞的MRI在3 T时显示出显著的对比度增强，T2* 短至161 ms，尽管用于细胞标记的MnAMP浓度相对较低且孵育时间较短。总体而言，MnAMP是为细胞MRI开发的最有效的细胞标记剂之一。
