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Host–guest inclusion systems of nedaplatin with cucurbit[7]uril for improved in vitro antitumour activity

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Abstract

Encapsulation of platinum-based anticancer drugs inside cucurbit[n]urils provides a steric hindrance to drug degradation. This study describes an alternative strategy for the enhancement of in vitro antitumor activity of nedaplatin (NDP) by encapsulating it in the cavity of cucurbit[7]uril (CB[7]). The complexation stoichiometry, binding affinity and geometry were studied via reliable spectroscopic and physicochemical techniques. The stoichiometry of the inclusion complex was 1:1 and the stability constant (KS) value was found to be (2.89 ± 0.26) × 106 M−1 at 293 K, which suggested a favorable inclusion complexation system has been formed. In vitro cytotoxicity of the free NDP and complexed NDP (NDP@CB[7]) was examined by MTT assay using three human cancer cell lines: A549, HCT116, MCF-7. Interestingly, more cytotoxicity on MCF-7 was observed for NDP@CB[7] as compared with free drugs. In addition, NDP@CB[7] showed significantly improved cytotoxicity against A549 and HCT116 cells with up to almost threefold and twofold higher cytotoxicity than that of free NDP, indicating that the encapsulation of NDP in CB[7] can enhance the cytotoxicity of NDP in tested cancer cell lines. The formed species are shown to be stabilized in solution and the host–guest complexation between NDP and CB[7] may allow this strategy to be effective for potential use in drug delivery.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (NNSFC) (Nos. 21961017, 21642001, 21662021) and Yunnan Applied Basic Research Projects (Nos. 2018FA047 and 2018FB018), which are gratefully acknowledged.

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Authors and Affiliations

  1. Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, Yunnan, People’s Republic of China

    Chunyan Jia, Yunshuang Zhong, Xinzhong Zhang, Xiali Liao, Yamin Li, Bo Yang & Chuanzhu Gao

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  1. Chunyan Jia
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  2. Yunshuang Zhong
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Correspondence to Chuanzhu Gao.

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Jia, C., Zhong, Y., Zhang, X. et al. Host–guest inclusion systems of nedaplatin with cucurbit[7]uril for improved in vitro antitumour activity. J Incl Phenom Macrocycl Chem 97, 99–107 (2020). https://doi.org/10.1007/s10847-020-00988-x

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