Department of Chemistry, Shiraz University, Shiraz 71946-84795, Iran.
Department of Physics, Farhangian University, Tarbiat Moallem, Ave Niayesh Junction Farahzadi Blvd, Tehran 1939614464, Iran.
J Phys Chem B. 2021 Jun 3;125(21):5549-5558. doi: 10.1021/acs.jpcb.1c02648. Epub 2021 May 20.
Titanium dioxide (TiO) nanotubes are attractive materials for drug-delivery systems because of their biocompatibility, chemical stability, and simple preparation. In this study, we loaded TiO nanotubes with anticancer drug doxorubicin (DOX) experimentally and in all-atom molecular dynamics (MD) simulations. The release of doxorubicin from the nanotubes was studied by high-performance liquid chromatography (HPLC) and confocal Raman spectroscopy, and drug-release profiles were evaluated under various conditions. The polyethylene glycol (PEG) coating and capping of the nanotubes led to a marked increase in the water contact angles from about 16 to 33° in keeping with reduced wettability. The capping retarded the release rate without decreasing the overall release amount. The MD simulations further show that the DOX molecule diffusion coefficients () are in the order of 10 m/s. The DOX molecules show a plethora of short- and long-range H-bonding interactions with TiO nanotube walls and water. Calculated radial distribution functions (RDFs) and combined radial/angular distribution functions (CDFs) allowed gauging the strength of these hydrogen bonds. The strength does not fully correlate with the values of DOX atoms which we assign to the confinement of DOX and water in the tubes. The lifetimes of hydrogen bonds between the DOX atoms and water molecules are shorter than that of the DOXTiO interactions, and DOXDOX aggregation does not play an important role. These results suggest TiO nanotubes as promising candidates for controllable drug-delivery systems for DOX or similar antiproliferative molecules.
二氧化钛（TiO）纳米管由于其生物相容性、化学稳定性和简单的制备方法，成为药物输送系统的有吸引力的材料。在这项研究中，我们通过实验和全原子分子动力学（MD）模拟将抗癌药物阿霉素（DOX）负载到 TiO 纳米管中。通过高效液相色谱（HPLC）和共聚焦拉曼光谱研究了阿霉素从纳米管中的释放情况，并在各种条件下评估了药物释放曲线。PEG 涂层和纳米管的封端导致水接触角从约 16°增加到 33°，从而降低了润湿性。封端虽然没有降低整体释放量，但减缓了释放速度。MD 模拟进一步表明，DOX 分子的扩散系数（）在 10 m/s 的量级。DOX 分子与 TiO 纳米管壁和水之间表现出大量的短程和远程氢键相互作用。计算的径向分布函数（RDF）和组合径向/角度分布函数（CDF）允许衡量这些氢键的强度。强度与 DOX 原子的 值不完全相关，我们将其归因于 DOX 和水在管内的限制。DOX 原子与水分子之间氢键的寿命短于 DOXTiO 相互作用的寿命，并且 DOX-DOX 聚集没有发挥重要作用。这些结果表明 TiO 纳米管是用于 DOX 或类似抗增殖分子的可控药物输送系统的有前途的候选材料。
