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用于优化高 T1 和 T2 加权对比能力与低血凝和细胞毒性之间平衡的纳米颗粒锰-六铼簇配合物的分子和纳米结构优化

Molecular and Nano-Structural Optimization of Nanoparticulate Mn-Hexarhenium Cluster Complexes for Optimal Balance of High T- and T-Weighted Contrast Ability with Low Hemoagglutination and Cytotoxicity.

作者信息

Akhmadeev Bulat Salavatovich, Nizameev Irek R, Kholin Kirill V, Voloshina Alexandra D, Gerasimova Tatyana P, Gubaidullin Aidar T, Kadirov Marsil K, Ismaev Ildus E, Brylev Konstantin A, Zairov Rustem R, Mustafina Asiya R

机构信息

A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, 8 Arbuzov Str., 420088 Kazan, Russia.

Department of Electronic Instrumentation and Quality Management, A.N. Tupolev Kazan Research Technological University, 420015 Kazan, Russia.

出版信息

Pharmaceutics. 2022 Jul 20;14(7):1508. doi: 10.3390/pharmaceutics14071508.

Abstract

The present work introduces rational design of nanoparticulate Mn(II)-based contrast agents through both variation of the μ (inner) ligands within a series of hexarhenium cluster complexes [{Re(μ-Q)}(CN)] (ReQ, Q = S, Se or Te) and interfacial decoration of the nanoparticles (NPs) KMnReQ ( = 1.3 - 1.8) by a series of pluronics (F-68, P-123, F-127). The results highlight an impact of the ligand and pluronic for the optimal colloid behavior of the NPs allowing high colloid stability in ambient conditions and efficient phase separation under the centrifugation. It has been revealed that the KMnReSe NPs and those decorated by F-127 are optimal from the viewpoint of magnetic relaxivities r and r (8.9 and 10.9 mMs, respectively, at 0.47 T) and low hemoagglutination activity. The insignificant leaching of Mn ions from the NPs correlates with their insignificant effect on the cell viability of both M-HeLa and Chang Liver cell lines. The T- and T-weighted contrast ability of F-127-KMnReQ NPs was demonstrated through the measurements of phantoms at whole body 1.5 T scanner.

摘要

本工作通过一系列六铼簇配合物[{Re(μ-Q)}(CN)](ReQ,Q = S、Se或Te)中μ(内)配体的变化以及一系列普朗尼克(F-68、P-123、F-127)对纳米颗粒(NPs)KMnReQ( = 1.3 - 1.8)的界面修饰,介绍了基于纳米颗粒的锰(II)造影剂的合理设计。结果突出了配体和普朗尼克对纳米颗粒最佳胶体行为的影响,使纳米颗粒在环境条件下具有高胶体稳定性,并在离心作用下实现有效相分离。从磁弛豫率r1和r2(在0.47 T时分别为8.9和10.9 mM s)以及低血凝活性的角度来看,已表明KMnReSe纳米颗粒和那些用F-127修饰的纳米颗粒是最佳的。纳米颗粒中锰离子的微量浸出与其对M-HeLa和Chang肝细胞系细胞活力的微小影响相关。通过在全身1.5 T扫描仪上对体模进行测量,证明了F-127-KMnReQ纳米颗粒的T1加权和T2加权造影能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de96/9316779/ffe10cc708ff/pharmaceutics-14-01508-g001.jpg

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