Biocompatible Fe-Based Micropore Metal-Organic Frameworks as Sustained-Release Anticancer Drug Carriers

摘要

Sustained-release preparation is a hot spot in antitumor drug research, where the first task is to select suitable drug carriers. Research has revealed that carboxylic acid iron metal–organic frameworks (MOFs), constructed from iron (Fe) ions and terephthalic acid, are nontoxic and biocompatible. Due to the breathing effect, the skeleton of this mesoporous material is flexible and can reversibly adapt its pore size through drug adsorption. Therefore, we chose one kind of Fe-MOF, MIL-53(Fe), as a carrier for the anticancer drug oridonin (Ori). In this work, we report the design and synthesis of MIL-53(Fe) and explore its ability as a transport vehicle to deliver Ori. MIL-53(Fe) is characterized by scanning electron microscopy and X-ray powder diffraction. A loading capacity of 56.25 wt % was measured by high performance liquid chromatography. This carrier was safe and nontoxic (cell viability > 95.27%), depending on the results of 3-(4,5-dimethylthiazol-2-yl)--2,5-diphenyltetrazolium bromide assays, lactate dehydrogenase assays, and Annexin V-fluoresce isothiocyanate/propidium iodide double-staining assays. After loading the drug, the structure of the MIL-53(Fe) was not destroyed, and Ori was amorphous in MIL-53(Fe). Based on an analysis of the Ori release profile, results suggest that it lasts for more than seven days in vitro. The cumulative release rate of Ori at the seventh day was about 82.23% and 91.75% in phosphate buffer saline solution at 37 °C under pH 7.2 and pH 5.5, respectively. HepG2 cells were chosen to study the cytotoxicity of Ori@MIL-53(Fe), and the results show that the anticancer ratio of Ori@MIL-53(Fe) system reaches 90.62%. Thus, MIL-53 can be used as a carrier for anticancer drugs and Ori@MIL-53(Fe) is a promising sustained-release drug delivery system for the cancer therapy.