Molecular and Nano-Structural Optimization of Nanoparticulate Mn2+-Hexarhenium Cluster Complexes for Optimal Balance of High T1- and T2-Weighted Contrast Ability with Low Hemoagglutination and Cytotoxicity

• Published in: Pharmaceutics Vol. 14; no. 7; p. 1508
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 20-07-2022; MDPI
• Subjects: Aqueous solutions; Blood; Copolymers; Cytotoxicity; hexarhenium clusters; Ligands; manganese based contrast agents; MRI; nanoparticles; Physiology; Japan
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics14071508

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.