Low Cytotoxic Metal-Organic Frameworks as Temperature-Responsive Drug Carriers

Two zinc-based porous metal-organic frameworks, ZJU-64 and ZJU-64-CH₃ , sharing the same crystal structure, have been synthesized from zinc ions, the biomolecular linker adenine, and carboxylate-based ligands, resulting in 3D frameworks with 1D channels (approximately 1.6 nm×1.9 nm). The materials ZJU-64 and ZJU-64-CH₃ exhibit low toxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay, microscopy images, and cell-cycle analysis; this indicates their potential applications for human health care. The anticancer drug methotrexate (MTX) is successfully loaded into MOFs by a simple impregnation method and the drug payloads reach approximately 13.45 and 10.63 wt % for ZJU-64 and ZJU-64-CH₃ , respectively. The sustainable drug-release behavior of MTX from MTX-loaded ZJU-64 and ZJU-64-CH₃ is detected for several days. The temperature-responsive deliveries of ZJU-64 and ZJU-64-CH₃ reveal that hyperthermia can control the drug release and open up a new treatment which combines drug therapy and thermal therapy to kill more cancer cells with fewer side effects; this reveals the practical value of ZJU-64 and ZJU-64-CH₃ as "smart" drug carriers with more therapeutic efficacy.