A new approach for the ultra-high loading of curcumin onto a nano-sized ZIF-68 as an effective drug delivery system with good biocompatibility and efficient anti-cancer therapy

Abstract

Recently, metal–organic frameworks have become well-known as promising drug carrier systems for anticancer treatment. However, their performances are inadequate for real-life situations due to the uncontrolled drug release rate and lack of strong interactions between the backbone and guest molecules. To overcome these challenges, a nano-sized zeolite imidazole framework-68 was successfully prepared, denoted as ZIF-68, through the solvothermal technique, and demonstrated an extraordinary potential for curcumin (Cur) uptake. As a consequence, the maximum adsorption capacity and drug loading content of Cur over ZIF-68 reached 720.1 mg g⁻¹ and 42.0%, respectively, which are much greater than those previously reported for drug carriers. These results best fit the Langmuir isothermal and pseudo-second-order models, indicating that the chemical interaction is dominant throughout the loading process. Furthermore, the Cur uptake mechanism is elucidated by the formation of robust attractions involving electrostatic interactions, π–π stacking, and hydrogen bonding between the drug molecules and the framework. This led to controlled drug release rates in human physiological medium (pH 7.4) and the tumor microenvironment (pH 5.0), thereby avoiding the “burst effect” at the initial stage. Remarkably, ZIF-68, after Cur loading (Cur@ZIF-68), was tested for cytotoxicity against HDF normal cells and MCF-7 cancer cells. As a result, Cur@ZIF-68 shows good biocompatibility with HDF cells and high cytotoxicity against MCF-7 cells at 25 µg mL⁻¹. These studies demonstrate that ZIF-68 is a promising candidate for an effective drug delivery system in anticancer therapy and support future research directions in designing porous materials capable of efficient drug carrying to support subsequent in vivo experiments.