Molecular and Nano-Structural Optimization of Nanoparticulate Mn<sup>2+</sup>-Hexarhenium Cluster Complexes for Optimal Balance of High T<sub>1</sub>- and T<sub>2</sub>-Weighted Contrast Ability with Low Hemoagglutination and Cytotoxicity
Bulat Salavatovich Akhmadeev,
Irek R. Nizameev,
Kirill V. Kholin,
Alexandra D. Voloshina,
Tatyana P. Gerasimova,
Aidar T. Gubaidullin,
Marsil K. Kadirov,
Ildus E. Ismaev,
Konstantin A. Brylev,
Rustem R. Zairov,
Asiya R. Mustafina
Affiliations
Bulat Salavatovich Akhmadeev
A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, 8 Arbuzov Str., 420088 Kazan, Russia
Irek R. Nizameev
A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, 8 Arbuzov Str., 420088 Kazan, Russia
Kirill V. Kholin
A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, 8 Arbuzov Str., 420088 Kazan, Russia
Alexandra D. Voloshina
A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, 8 Arbuzov Str., 420088 Kazan, Russia
Tatyana P. Gerasimova
A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, 8 Arbuzov Str., 420088 Kazan, Russia
Aidar T. Gubaidullin
A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, 8 Arbuzov Str., 420088 Kazan, Russia
Marsil K. Kadirov
A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, 8 Arbuzov Str., 420088 Kazan, Russia
Ildus E. Ismaev
Department of Electronic Instrumentation and Quality Management, A.N. Tupolev Kazan Research Technological University, 420015 Kazan, Russia
Konstantin A. Brylev
Nikolaev Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, 3 Acad. Lavrentiev Ave., 630090 Novosibirsk, Russia
Rustem R. Zairov
A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, 8 Arbuzov Str., 420088 Kazan, Russia
Asiya R. Mustafina
A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, 8 Arbuzov Str., 420088 Kazan, Russia
The present work introduces rational design of nanoparticulate Mn(II)-based contrast agents through both variation of the μ3 (inner) ligands within a series of hexarhenium cluster complexes [{Re6(μ3-Q)8}(CN)6]4− (Re6Q8, Q = S2−, Se2− or Te2−) and interfacial decoration of the nanoparticles (NPs) K4−2xMnxRe6Q8 (x = 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 K4−2xMnxRe6Se8 NPs and those decorated by F-127 are optimal from the viewpoint of magnetic relaxivities r1 and r2 (8.9 and 10.9 mM−1s−1, respectively, at 0.47 T) and low hemoagglutination activity. The insignificant leaching of Mn2+ ions from the NPs correlates with their insignificant effect on the cell viability of both M-HeLa and Chang Liver cell lines. The T1- and T2-weighted contrast ability of F-127–K4−2xMnxRe6Q8 NPs was demonstrated through the measurements of phantoms at whole body 1.5 T scanner.