Mahdavi Mina, Fattahi Ali, Tajkhorshid Emad, Nouranian Sasan
Department of Chemical Engineering, The University of Mississippi, University, MS 38677, United States.
School for Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ 85287, United States.
ACS Appl Bio Mater. 2020 Mar 16;3(3):1354-1363. doi: 10.1021/acsabm.9b00956. Epub 2020 Feb 12.
Molecular dynamics (MD) simulations were performed to investigate the loading and dynamics of doxorubicin (DOX) anticancer drug on graphene oxide (GO) and poly(ethylene glycol) (PEG) decorated GO (PEGGO) nanocarriers in an aqueous environment at human body temperature (310 K) and physiological pH level of 7.4. Mechanisms of DOX adsorption on PEGGO as a function of PEG chain length were revealed. While the total DOX-nanocarrier interaction energy was the same for the DOX/GO (control), DOX/Sh-PEGGO (short PEG chains consisting of 15 repeat units), and DOX/L-PEGGO (long PEG chains consisting of 30 repeat units) within the margin of error, the PEG-DOX interactions increased with an increase in the PEG chain length. At the same time, the PEG-DOX solvent-accessible contact area almost doubled going from the short to long PEG chains. PEGylation of the GO effectively causes an increase in the average water density around the nanocarrier, which can act as a barrier, leading to the DOX migration to the solvated PEG-free part of the GO surface. This effect is more pronounced for shorter PEG chains. The DOX-DOX solvent-accessible contact area is smaller in the DOX/GO system, which means the drug molecules are less aggregated in this system. However, the level of DOX aggregation is slightly higher for the PEGGO systems. The computational results in this work shed light on the fact that increasing the PEG chain length benefits DOX loading on the nanocarrier, revealing an observation that is difficult to acertain through experiments. Moreover, a detailed picture is provided for the DOX adsorption and retention in PEGGO drug delivery systems, which would enable the researchers to improve the drug's circulation time, as well as its delivery and targeting efficiency.
进行了分子动力学（MD）模拟，以研究阿霉素（DOX）抗癌药物在人体温度（310 K）和生理pH值7.4的水性环境中，在氧化石墨烯（GO）和聚乙二醇（PEG）修饰的GO（PEGGO）纳米载体上的负载和动力学。揭示了DOX在PEGGO上的吸附机制与PEG链长度的关系。虽然在误差范围内，DOX/GO（对照）、DOX/Sh-PEGGO（由15个重复单元组成的短PEG链）和DOX/L-PEGGO（由30个重复单元组成的长PEG链）的总DOX-纳米载体相互作用能相同，但PEG-DOX相互作用随着PEG链长度的增加而增加。同时，从短PEG链到长PEG链，PEG-DOX溶剂可及接触面积几乎翻倍。GO的聚乙二醇化有效地导致纳米载体周围平均水密度增加，这可以起到屏障作用，导致DOX迁移到GO表面无溶剂化PEG的部分。这种效应在较短的PEG链中更为明显。在DOX/GO系统中，DOX-DOX溶剂可及接触面积较小，这意味着该系统中药物分子的聚集较少。然而，PEGGO系统中DOX的聚集程度略高。这项工作的计算结果揭示了增加PEG链长度有利于DOX在纳米载体上的负载这一事实，这是通过实验难以确定的观察结果。此外，还提供了DOX在PEGGO药物递送系统中的吸附和保留的详细情况，这将使研究人员能够改善药物的循环时间及其递送和靶向效率。
