Synergistic Effects of Anticancer Drug Delivered via Nanoporous Zeolitic Imidazolate Frameworks: Implications for Tumor Therapy

Due to the resistance and toxicity of existing anticancer agents, it forces people to continuously develop antitumor drugs that can overcome these side effects. Herein, we designed and synthesized a trifluoromethyl-containing triazole derivative compound TBHPC (tert-butyl (2-(3-(2-hydroxy-4-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-5-yl)phenyl) carbonate). It displays abundant physical properties, such as high thermostability and an obvious pH response. As drug delivery is considered a practical technology, it has been applied for the delivery of the required cargo for tumor therapy. Thus, the nanoporous zeolitic imidazolate framework-8 (ZIF-8), featuring a large specific surface area and porosity, was used to convey TBHPC for a synergistic antitumor effect. Because of the high loading rate of ZIF-8 (10.6 wt %) and the synergistic effect of different components in restrained malignant cells, nearly 60% of H22 cells treated with ZIF-8/TBHPC at a concentration of 5 μg/mL were killed after 24 h of incubation, which exceeded the capacity of pure TBHPC. Moreover, pathological sections showed that ZIF-8/TBHPC showed low biotoxicity to normal tissue in the mice. Furthermore, the intratumoral application of ZIF-8/TBHPC greatly inhibited tumor growth in H22 tumor-bearing mice. Therefore, this ZIF-8/TBHPC system can be regarded as an alternative tactic to fight malignant tumors.