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Prolonged cytostatic effect of nanosized NH2-UiO-66 doped with doxorubicin

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Abstract

Nanosized (d ∼70 nm) particles of metal-organic framework (MOF) based on zirconium and 2-aminoterephthalic acid, NH2-UiO-66, were prepared by a simple one-pot method. Due to the small particle size, the presence of amino groups, low toxicity, and high sorption capacity caused by large pore size, the obtained MOF is a perfect platform for the preparation of combined cytostatic agents with prolonged action. Nano-MOF is highly stable in distilled water, which allows for the sorption of a cytostatic drug without crystal destruction. The MOF gradually loses crystallinity in phosphate-buffered saline (pH 7.4), resulting in a gradual release of the drug under near-physiological conditions. Sorption studies have shown that approximately 50% of the drug is adsorbed after 48 h of storage of NH2-UiO-66 in a doxorubicin solution. To demonstrate the prolonged cytostatic effect, cytotoxicity was studied for different incubation times (8, 24, and 48 h) against two cell cultures, MRC-5 (fibroblasts, healthy cells) and Hep-2 (human laryngeal cancer cells). Doxorubicin-doped nano-MOF shows the highest toxicity, which increases with increasing incubation time, thus confirming prolonged cytostatic effect.

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Authors and Affiliations

  1. Nikolaev Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, 3 prosp. Akad. Lavrentieva, 630090, Novosibirsk, Russian Federation

    A. V. Konkova, D. I. Konovalov, T. N. Pozmogova, A. A. Ivanov, Yu. A. Vorotnikov & M. A. Shestopalov

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  1. A. V. Konkova
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  2. D. I. Konovalov
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  3. T. N. Pozmogova
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  4. A. A. Ivanov
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  5. Yu. A. Vorotnikov
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  6. M. A. Shestopalov
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Correspondence to Yu. A. Vorotnikov or M. A. Shestopalov.

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Mikhail Aleksandrovich Shestopalov, born in 1984, Doctor of Chemical Sciences, Head of the Laboratory of Bioactive Inorganic Compounds of the Nikolaev Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, Candidate for Professor of RAS at the election of 2022. M. A. Shestopalov specializes in cluster chemistry (mainly octahedral Mo, W, and Re cluster complexes) and cluster-containing materials and their potential applications in various fields, including biomedical applications such as photodynamic therapy and luminescent imaging. M. A. Shestopalov is the author of 94 scientific papers and seven patents. He supervised research and defense of two PhD Theses. He is a winner of the Prize of Novosibirsk Mayor’s Office in Science and Innovations in the category “The best young researcher in science organizations” (2019) and the Name Prize of the Government of the Novosibirsk Region in the category “The best research supervisor” (2020). He is an expert of the Russian Science Foundation (since 2020) and a RAS expert (since December, 2021).

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, Vol. 72, No. 2, pp. 574–581, February, 2023.

The authors are grateful to the Center for the Collective Use of Microscopic Analysis of Biological Objects, Siberian Branch of the Russian Academy of Sciences (http://www.bionet.nsc.ru/microscopy/), for the provided research equipment.

No human or animal subjects were used in this research.

The authors declare no competing interests.

This study was financially supported by the Russian Science Foundation (Project No. 20-73-00147) and the Ministry of Science and Higher Education of the Russian Federation (Project No. 121031700321-3).

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Konkova, A.V., Konovalov, D.I., Pozmogova, T.N. et al. Prolonged cytostatic effect of nanosized NH2-UiO-66 doped with doxorubicin. Russ Chem Bull 72, 574–581 (2023). https://doi.org/10.1007/s11172-023-3821-3

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