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Design and evaluation of folate-appended methyl-β-cyclodextrin as a new antitumor agent

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Abstract

Methyl-β-cyclodextrin (M-β-CyD) is widely used as a raft disrupting agent through extraction of cholesterol from lipid rafts which are highly expressed in cell membranes of tumor cells, but it does not have tumor cell-selective action. Meanwhile, the widespread use of folic acid (FA) as a tumor-targeting ligand has been known, because folate receptor (FR) overexpresses in various kinds of epithelial tumor cells. In the present study, in order to obtain more tumor cell-selectivity and antitumor activity of M-β-CyD, we designed folate-appended M-β-CyD (FA-M-β-CyD), and evaluated its physicochemical properties and antitumor activity. The 1H-NMR study demonstrated that FA-M-β-CyD having average degree of substitution of FA (DSF) of 1.0 was prepared. In addition, FA-M-β-CyD (DSF 1.0) was found to be amorphous in a solid state and surface-active. Importantly, FA-M-β-CyD (DSF 1.0) had potent cytotoxicity, compared to M-β-CyD in KB cells, but not in A549 cells. These results suggest that FA-M-β-CyD (DSF 1.0) has the potential as a novel antitumor agent.

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Acknowledgments

This work was partially supported by a Grant-in-Aid from Young Scientists (B) from the Ministry of Education, Science and Culture of Japan (22790040).

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Authors and Affiliations

  1. Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto, 862-0973, Japan

    Risako Onodera, Keiichi Motoyama & Hidetoshi Arima

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  1. Risako Onodera
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  2. Keiichi Motoyama
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  3. Hidetoshi Arima
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Correspondence to Hidetoshi Arima.

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Onodera, R., Motoyama, K. & Arima, H. Design and evaluation of folate-appended methyl-β-cyclodextrin as a new antitumor agent. J Incl Phenom Macrocycl Chem 70, 321–326 (2011). https://doi.org/10.1007/s10847-010-9843-z

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  • DOI: https://doi.org/10.1007/s10847-010-9843-z

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