Preliminary Study of the Anticancer Applications of Mesoporous Materials Functionalized with the Natural Product Betulinic Acid

Authors

  • Sergio Sánchez-Muñoz,

    1. Departamento de Química Inorgánica y Analítica, E.S.C.E.T. Universidad Rey Juan Carlos, 28933 Móstoles, Madrid (Spain)
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  • Dr. Santiago Gómez-Ruiz,

    Corresponding author
    1. Departamento de Química Inorgánica y Analítica, E.S.C.E.T. Universidad Rey Juan Carlos, 28933 Móstoles, Madrid (Spain)
    • Departamento de Química Inorgánica y Analítica, E.S.C.E.T. Universidad Rey Juan Carlos, 28933 Móstoles, Madrid (Spain)
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  • Dr. Damián Pérez-Quintanilla,

    Corresponding author
    1. Departamento de Química Inorgánica y Analítica, E.S.C.E.T. Universidad Rey Juan Carlos, 28933 Móstoles, Madrid (Spain)
    • Departamento de Química Inorgánica y Analítica, E.S.C.E.T. Universidad Rey Juan Carlos, 28933 Móstoles, Madrid (Spain)
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  • Dr. Sonia Morante-Zarcero,

    1. Departamento de Química Inorgánica y Analítica, E.S.C.E.T. Universidad Rey Juan Carlos, 28933 Móstoles, Madrid (Spain)
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  • Dr. Isabel Sierra,

    1. Departamento de Química Inorgánica y Analítica, E.S.C.E.T. Universidad Rey Juan Carlos, 28933 Móstoles, Madrid (Spain)
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  • Dr. Sanjiv Prashar,

    1. Departamento de Química Inorgánica y Analítica, E.S.C.E.T. Universidad Rey Juan Carlos, 28933 Móstoles, Madrid (Spain)
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  • Dr. Reinhard Paschke,

    1. Biozentrum der Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22, 06120 Halle (Germany)
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  • Dr. Goran N. Kaluđerović

    Corresponding author
    1. Biozentrum der Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22, 06120 Halle (Germany)
    • Biozentrum der Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22, 06120 Halle (Germany)
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Abstract

Dehydrated MCM-41 (S 1) was functionalized under nitrogen with 3-chloropropyltriethoxysilane (CPTS) and 3-aminopropyltriethoxysilane (APTS) by grafting in toluene at 80 °C over 48 h to give the corresponding materials S 2 and S 3, respectively. Subsequently, S 2 and S 3 were suspended in methanol and reacted in a nitrogen atmosphere with betulinic acid (BA) for 48 h at 65 °C (in the presence of the triethylamine of S 2) to give the BA-functionalized materials S 4 and S 5. All materials studied were characterized by powder X-ray diffraction, X-ray fluorescence, nitrogen gas sorption, multinuclear MAS NMR spectroscopy, thermogravimetry, UV spectroscopy, IR, SEM, and TEM. To study the release of BA, S 4 and S 5 were suspended in solutions simulating various body pH conditions (pH 7.4, 5.5, and 3.0). Results of the quantification of BA release by HPLC for S 4 show a pH-dependent and very slow BA release following a logarithmic tendency, while S 5 behaves differently, also pH-dependent but, in this case, fast release of BA which requires only days for total release of the therapeutic compound. In addition, the cytotoxic activity of all synthesized materials against various cancer cell lines was studied. The results show the absence of an antiproliferative effect on the surfaces without BA S 1S 3, while an antiproliferative effect was observed with S 4 and S 5 and was attributed to the release of BA in the medium.

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