Self-assembling nanoparticles based on acetate derivatives of calix[4]resorcinol and octenidine dihydrochloride for tuning selectivity in cancer cells

Abstract

The search for highly active and highly selective antitumor agents with minimal side effects remains an urgent task, since commercial anticancer drugs have a low selectivity index. Reducing the impact on normal tissues while maintaining a high anticancer potential should be a key parameter in the development of a dosage form. In recent years, a high anticancer activity of octenidine has been reported on various cell lines. However, being a cationic surfactant, octenidine has a high toxicity, which can be reduced by incorporating it into biocompatible nanoparticles. In this work, biomimetic vesicular systems based on amphiphilic calix[4]resorcinols functionalized along the upper rim with acetate groups and octenidine dihydrochloride were obtained. The morphology of the obtained aggregates was confirmed by transmission electron microscopy and dynamic light scattering data. Calixarene–octenidine nanoparticles showed high cytotoxic activity (IC50 =0.4 µM) toward the human duodenal adenocarcinoma HuTu 80 cell line, as well as high selectivity (Selectivity Index > 20), which makes it possible to consider calixarene–octenidine nanoparticles as promising drug candidates.