Boroushaki Tahereh, Dekamin Mohammad G, Hashemianzadeh Seyyed Majid, Naimi-Jamal Mohammad Reza, Ganjali Koli Mokhtar
Pharmaceutical and Heterocyclic Compounds Research Laboratory, Department of Chemistry, Iran University of Science and Technology, Tehran, 16846-13114, Iran.
Pharmaceutical and Heterocyclic Compounds Research Laboratory, Department of Chemistry, Iran University of Science and Technology, Tehran, 16846-13114, Iran.
J Mol Graph Model. 2022 Jun;113:108147. doi: 10.1016/j.jmgm.2022.108147. Epub 2022 Feb 18.
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.
靶向给药系统是减少副作用并提高药物治疗效果的有效方法。金属有机框架是一类新型多孔材料，由于其具有高比表面积、高孔隙率、低毒性、高载药量、可控药物释放、优异的生物相容性和生物降解性，最近已被用作医学应用中的高性能纳米载体，如药物储存和递送。在本研究中，使用分子动力学模拟方法研究了抗癌药物替莫唑胺、阿仑膦酸盐和5-氟尿嘧啶在UiO-66纳米载体腔内的原子水平负载情况以及不同药物浓度。研究了所有系统中药物与UiO-66的相互作用能、二维密度图和药物迁移率。结果发现，高浓度系统中的所有药物负载量均高于低浓度系统。在所使用的药物中，替莫唑胺更靠近UiO-66的中心，这表明其相互作用能更负。因此，与其他研究药物相比，替莫唑胺在UiO-66腔内负载具有更强的热力学倾向。二维密度研究表明，所有药物主要负载在金属中心上。替莫唑胺和阿仑膦酸盐负载在内中心，而5-氟尿嘧啶显示出更高的负载在表面金属中心的倾向。通过研究药物的迁移率，发现替莫唑胺由于与UiO-66的相互作用更强，其迁移率低于其他两种药物。
