A molecular dynamic simulation study of anticancer agents and UiO-66 as a carrier in drug delivery systems

Targeted drug delivery systems are effective ways to reduce side effects and enhance the therapeutic efficacy of drugs. Metal-organic frameworks are a new class of porous materials that have been recently used as high-performance nanocarriers in medical applications, such as drug storage and delivery due to high internal surface area, high porosity, low toxicity, high payloads, controlled drug release, their exceptional biocompatibility, and biodegradability. In this study, the loading of anti-cancer drugs Temozolomide, Alendronate, and 5-Fluorouracil inside UiO-66 nanocarrier cavities at the atomic level and different concentrations of the drug were investigated using the molecular dynamics simulation method. Drug interaction energies with UiO-66, two-dimensional density map, and drug mobility in all systems were investigated. It was found that all drugs in higher concentration systems have higher loads than less concentrated systems. Among the drugs used, Temozolomide was located closer to the center of UiO-66 which indicated more negative interaction energy. Therefore, Temozolomide has a more thermodynamic tendency to load inside the UiO-66 cavities than the other studied drugs. Two-dimensional density study showed that all drugs were mainly loaded on metal centers. Temozolomide and Alendronate were loaded on inner centers, although 5-Fluorouracil showed a higher tendency to load on surface metal centers. From studying the mobility of drugs, Temozolomide was less mobile than the other two drugs due to its stronger interaction with UiO-66.