Cytotoxicity and slow release of the anti-cancer drugdoxorubicin from ZIF-8

Abstract

Metal–organic frameworks are emerging as a powerful platform for the delivery and controlled release of several drug molecules. Herein, we report the incorporation of the anti-cancer drug doxorubicin into the zeolitic imidazolate framework (ZIF-8) with high-load and progressive release. Adsorption measurements show that doxorubicin is incorporated into ZIF-8 with a load of 0.049 g doxorubicin g⁻¹ dehydrated ZIF-8. Doxorubicin is released in a highly controlled and progressive fashion with 66% of the drug released after 30 days. We also characterize the antitumoral potential and cytotoxicity of the doxorubicin-ZIF-8 (DOXO-ZIF-8) complex towards the mucoepidermoid carcinoma of human lung (NCI-H292), human colorectal adenocarcinoma (HT-29), and human promyelocytic leukemia (HL-60) cell lines. It is shown that the complex doxorubicin-ZIF-8 exhibits lower cytotoxicity than pure doxorubicin for the tested cells, possibly due to the slower release of the incorporated drug. Furthermore, host–guest interactions have been addressed from a microscopic perspective through molecular docking simulations. In conjunction with our experimental characterization, the calculations suggest that doxorubicin binds preferentially to the surface rather than into the pores of ZIF-8, whose entry diameter is at least half the size of the shortest axis of the drug. These findings are also consistent with high-resolution X-ray crystallography and NMR spectroscopy studies of ZIF-8 which shows that this framework is very rigid under constant pressure in contrast to previous experimental and theoretical studies of ZIF-8 under gas pressure.