Manganese Oxide Nanoparticles Inhibit the Growth of Subcutaneous U-87MG Glioblastoma Xenografts in Immunodeficient Mouse
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Cell Technologies in Biology and Medicine, No. 3, November, 2020
Manganese Oxide Nanoparticles Inhibit the Growth of Subcutaneous U-87MG Glioblastoma Xenografts in Immunodeficient Mouse I. A. Razumov1,3, S. Yu. Troitskii2, O. I. Solov’eva1,3, N. D. Boldyrev1,3, and E. L. Zavjalov1,3
Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 3, pp. 191-196, September, 2020 Original article submitted May 20, 2020 Our previous study demonstrated that manganese oxide nanoparticles (MnO NP) selectively destroyed U-87MG and U251 human glioblastoma cells in vitro. MnO NP were synthesized and studied by electron microscopy. Their antitumor properties were studied in vivo on the model of immunodeficient SCID mice with subcutaneous xenografts of U-87MG human glioblastoma. The mice were injected subcutaneously with MnO NP in doses of 0.96 and 1.92 mg/kg (calculated for Mn) 3 days a week over 3 weeks. In was shown that MnO NP in these doses significantly suppressed the growth of U-87MG glioblastoma xenografts: on day 21 from the start of the treatment, the tumor growth inhibition index was 61.1 and 99.22%, respectively. These results indicate the necessity of the further studies of MnO NP as a potential oncolytic agent for the therapy of human glioblastomas. Key Words: nanoparticles; manganese oxide; glioblastoma; xenotransplantation; U-87MG
Gliomas are most common primary brain tumors. The most malignant among them are glioblastomas, their active proliferation is fatal in most cases. Despite some progress in treating gliomas achieved in recent decades, the median survival after diagnosing of glioblastoma remains ~15 months [3]. There is no downward trend but an ever increase in the morbidity after malignant cerebral glioma. Nanomaterials are now used as diagnostic tools, delivery agents, and therapeutic anti-tumor agent [11,15,19]. Nanoparticles (NP) of metal oxides are of particular interest. It is shown that nanoparticles of some metal oxides can kill tumor cells without producing cytotoxic effect on healthy cells in the same 1 Federal Research Center Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences, Novosibirsk, Russia; 2Federal Research Center G. K. Boreskov Institute of Catalysis, Siberian Division of the Russian Academy of Sciences, Novosibirsk, Russia; 3Novosibirsk National Research State University, Novosibirsk, Russia. Address for correspondence: [email protected]. I. A. Razumov
doses [6,8,12,18]. For example, nanoparticles of cobalt, iron, titanium, zinc, cerium, and copper oxides have direct cytotoxic effect on tumor cells in vitro; NP of cerium, titanium, and copper suppress tumor growth of laboratory animals. The antitumor activity is demonstrated by metal oxide NP alone and their combinations with the other types of treatment such as photocatalytic therapy, hyperthermia, and synergistic treatment (irradiation) and oncolytic preparations [5,14,20]. Moreover, modification of NP can improve their selectivity to tumor cells in vitro and in vivo and reduce th
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