Mashayekh Elham, Ghiasi Zahra Nouri Khajeh, Bhia Iman, Khorrami Zohreh Arefi, Malekahmadi Omid, Bhia Mohammed, Malekmohammadi Samira, Ertas Yavuz Nuri
Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 14115, Iran.
Department of Chemical Engineering, Islamic Azad University, Shahrood Branch, Shahrood 36155163, Iran.
ACS Omega. 2024 Apr 22;9(17):19627-19636. doi: 10.1021/acsomega.4c01437. eCollection 2024 Apr 30.
Metal-organic frameworks (MOFs) are utilized as nanocarriers to enhance the efficiency of chemotherapy drugs, including cisplatin, which exhibit limitations such as side effects and resistance mechanisms. To evaluate the role of MOFs, we employed a molecular dynamics simulation, which, unlike other experiments, is cost-effective, less dangerous, and provides accurate results. Furthermore, we conducted molecular docking simulations to understand the interaction between cisplatin and MOF, as well as their internal interactions and how they bind to each other. Cisplatin and MOF molecules were parametrized using the Avogadro software and x2top command in GROMACS 5.1.2 and optimized by CP2K software; the Charmm-GUI site parametrized the cell cancer membrane. Three molecular dynamics simulations were conducted in four stages at various pHs, followed by simulated umbrella sampling. The simulations analyzed the pH responsiveness, total energy, Gibbs free energy, gyration radius, radial distribution function (RDF), solvent accessible surface area, and nanoparticles' toxicity. Results demonstrated that a neutral pH level (7.4) has greater adsorption and interaction compared to acidic pH values (6.4 and 5.4) because it displays the highest total energy (-17.1 kJ/mol), the highest RDF value (6.66), and the shortest distance (0.51 nm). Furthermore, the combination of cisplatin and MOFs displayed increased penetration compared to that of their individual forms. This study highlights the suitability of MOFs as nanocarriers and identifies the optimal pH values for desirable outcomes. Thus, it provides future studies with appropriate data to conduct their experiments in assessing MOFs.
金属有机框架（MOFs）被用作纳米载体，以提高包括顺铂在内的化疗药物的疗效，这些化疗药物存在副作用和耐药机制等局限性。为了评估MOFs的作用，我们采用了分子动力学模拟，与其他实验不同，该模拟具有成本效益、危险性较低且能提供准确结果的特点。此外，我们进行了分子对接模拟，以了解顺铂与MOF之间的相互作用，以及它们的内部相互作用和彼此的结合方式。使用Avogadro软件和GROMACS 5.1.2中的x2top命令对顺铂和MOF分子进行参数化，并通过CP2K软件进行优化；Charmm-GUI网站对细胞癌膜进行参数化。在不同pH值下分四个阶段进行了三次分子动力学模拟，随后进行了模拟伞形采样。模拟分析了pH响应性、总能量、吉布斯自由能、回转半径、径向分布函数（RDF）、溶剂可及表面积和纳米颗粒的毒性。结果表明，与酸性pH值（6.4和5.4）相比，中性pH值（7.4）具有更强的吸附和相互作用，因为它显示出最高的总能量（-17.1 kJ/mol）、最高的RDF值（6.66）和最短的距离（0.51 nm）。此外，与单独形式相比，顺铂和MOFs的组合显示出更高的渗透性。本研究突出了MOFs作为纳米载体的适用性，并确定了实现理想结果的最佳pH值。因此，它为未来的研究提供了适当的数据，以便在评估MOFs时进行实验。
