Experimental and theoretical investigation of phytochemical euphol incorporated in ZIF-8 as a drug delivery system for cancer treatment

Cancer is one of the main causes of human death around the world. Nature can be a powerful source of bioactives with strong anticancer activity. Euphol, a triterpene alcohol extracted from the sap of E. tirucalli possesses antitumoral activity and could be a viable alternative for cancer treatment. However, drug delivery strategies could be required to minimize its toxicity and improve its stability. Metal-organic frameworks (MOFs) stand out among systems used as platforms for drug delivery. In this work, we report the extraction and isolation of euphol from nature, its adsorption in nanosized ZIF-8 (zeolitic imidazolate framework) with high-load, and we study the efficacy of this system against cancer cells. The ZIF-8 loaded with euphol is characterized by X-ray diffraction, infrared spectroscopy and scanning electron microscopy. To gain insights into the incorporation mechanism, host-guest interactions have been investigated through molecular docking simulations, suggesting that the interaction occurs at the surface, being driven mainly by euphol's hydroxyl binding to the Zn2+ cations on the framework as well as 7C -7C staking interactions. Finally, in vitro investigations reveal that ZIF-8 considerably enhances the effectivity of euphol against cancer cell lines, while displaying selectivity for targeting cancer cells instead of healthy cells. This is the first report of the incorporation of euphol in a drug delivery system. The findings from this study can guide the development of novel biomaterials for cancer treatment.

Automated summary

This study reports the extraction and isolation of euphol from nature, its adsorption in nanosized ZIF-8, and the efficacy of this system against cancer cells. Experimental and simulation results show that ZIF-8 can enhance the effectiveness of euphol against cancer cells and selectively target cancer cells.