Supramolecular alleviation of cardiotoxicity of a small-molecule kinase inhibitor

Xue Yang (1) , Qiaoxian Huang , David Bardelang (2) , Chunming Wang (3) , Simon M. Y. Lee (1) , Ruibing Wang (4)

1 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China
2 ICR - Institut de Chimie Radicalaire
3 STL - Savoirs, Textes, Langage (STL) - UMR 8163
4 Institute of Chinese Medical Sciences - State Key Laboratory of Quality Research in Chinese Medicine Taipa, Macau SAR,

Small-molecule kinase inhibitors (SMKIs) have been widely used in the treatment of a variety of cancers due to their clinically demonstrated efficacy. However, the use of some SMKIs, such as sorafenib (SO), has been plagued by their cardiotoxicity that has been frequently observed in treated patients. Herein we report that the encapsulation of SO by a synthetic receptor cucurbit[7]uril (CB[7]) alleviated the inherent cardiotoxicity of SO, as demonstrated in an in vivo zebrafish model. Moreover, the anti-cancer activity of SO was well preserved, upon its encapsulation by CB[7], as demonstrated by both in vitro and in vivo cancer/angiogenesis models. This discovery may provide new insights into a novel supramolecular formulation of SMKIs for the management of their side-effects.

Keywords: angiogenesis; bioavailability; cancer; complexation; drug; encapsulation; Hepatotoxicity; sorafenib; synthetic receptor; zebrafish

Domains: Chemical Sciences

Xue Yang, Qiaoxian Huang, David Bardelang, Chunming Wang, Simon M. Y. Lee, et al.. Supramolecular alleviation of cardiotoxicity of a small-molecule kinase inhibitor. Organic & Biomolecular Chemistry, 2017, 15 (38), pp.8046--8053. ⟨10.1039/c7ob01505d⟩. ⟨hal-01774176⟩