Computational Biology and Chemistry Group (CBCG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
Department of Chemical Engineering, Amirkabir University of Technology (Tehran Polytechnic), 424 Hafez Avenue, Tehran, Iran.
Sci Rep. 2021 Nov 2;11(1):21538. doi: 10.1038/s41598-021-00817-2.
Here, molecular dynamics (MD) simulations were employed to explore the self-assembly of polymers and docetaxel (DTX) as an anticancer drug in the presence of nitrogen, phosphorous, and boron-nitrogen incorporated graphene and fullerene. The electrostatic potential and the Gibbs free energy of the self-assembled materials were used to optimize the atomic doping percentage of the N- and P-doped formulations at 10% and 50%, respectively. Poly lactic-glycolic acid (PLGA)- polyethylene glycol (PEG)-based polymeric nanoparticles were assembled in the presence of nanocarbons in the common (corresponding to the bulk environment) and interface of organic/aqueous solutions (corresponding to the microfluidic environment). Assessment of the modeling results (e.g., size, hydrophobicity, and energy) indicated that among the nanocarbons, the N-doped graphene nanosheet in the interface method created more stable polymeric nanoparticles (PNPs). Energy analysis demonstrated that doping with nanocarbons increased the electrostatic interaction energy in the self-assembly process. On the other hand, the fullerene-based nanocarbons promoted van der Waals intramolecular interactions in the PNPs. Next, the selected N-doped graphene nanosheet was utilized to prepare nanoparticles and explore the physicochemical properties of the nanosheets in the permeation of the resultant nanoparticles through cell-based lipid bilayer membranes. In agreement with the previous results, the N-graphene assisted PNP in the interface method and was translocated into and through the cell membrane with more stable interactions. In summary, the present MD simulation results demonstrated the success of 2D graphene dopants in the nucleation and growth of PLGA-based nanoparticles for improving anticancer drug delivery to cells, establishing new promising materials and a way to assess their performance that should be further studied.
在这里，采用分子动力学（MD）模拟方法研究了聚合物和多西紫杉醇（DTX）在氮、磷和硼氮共掺杂石墨烯和富勒烯的存在下自组装为药物载体的情况。使用静电势和自组装材料的吉布斯自由能优化了 N 和 P 掺杂配方的原子掺杂百分比，分别为 10%和 50%。在纳米碳的存在下，组装了聚乳酸-聚乙二醇（PLGA）-聚乙二醇（PEG）基聚合物纳米粒，存在于有机/水溶液的界面（对应于微流控环境）。对模型结果（如大小、疏水性和能量）的评估表明，在纳米碳中，界面法中的 N 掺杂石墨烯纳米片形成了更稳定的聚合物纳米粒（PNP）。能量分析表明，纳米碳的掺杂增加了自组装过程中的静电相互作用能。另一方面，富勒烯基纳米碳促进了 PNP 中的范德华分子内相互作用。接下来，选择了 N 掺杂石墨烯纳米片来制备纳米粒，并研究了纳米片在通过基于细胞的脂质双层膜的纳米粒渗透过程中的物理化学性质。与之前的结果一致，N-掺杂石墨烯辅助界面法中的 PNP，并通过细胞膜进行转运，具有更稳定的相互作用。总之，本 MD 模拟结果表明，二维石墨烯掺杂剂在基于 PLGA 的纳米粒的成核和生长中取得了成功，可改善抗癌药物向细胞的传递，为新的有前途的材料的建立和其性能的评估提供了一种方法，值得进一步研究。
