Mechanism and structure of the interaction of water-soluble pillar[5] arene and ibrutinib that enhances the anticancer activity of ibrutinib

摘要

Direct host-guest encapsulation of anticancer drugs by pillararenes is an effective approach to overcome their several disadvantages. In the present work, the potential application of water-soluble pillar[5]arene (WP5) on enhancing the bioactivity of ibrutinib (IBR) was evaluated. Nuclear magnetic resonance (NMR), ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, and fluorescence spectroscopy results showed that IBR could form a medium-strength complex with WP5 in solution (K = (2.13 +/- 0.10) x 10(4) M-1). Under this binding affinity, IBR could be slowly and steadily released from the complex. Studies on proton NMR and molecular modeling confirmed that the piperidine moiety of IBR entered the electron-rich cavity of WP5. CH-pi and hydrophobic interactions played major roles in IBR -WP5 binding. These amphiphilic complexes assembled into vesicles with an average diameter of 307.6 nm in aqueous solution. Some IBR were encapsulated in the vesicles. Such vesicles had a good stability (zeta-potential = -41.2 mV). Therefore, WP5 could effectively enhance the anticancer efficiency of IBR on CT26 cells although it had no special functions. (C) 2020 Elsevier B.V. All rights reserved.