Zeng Songwei, Ji Yu, Shen Yue, Zhu Ruiyao, Wang Xiaogang, Chen Liang, Chen Junlang
School of Information and Industry, Zhejiang A&F University Lin'an 311300 China
Department of Optical Engineering, Zhejiang A&F University Lin'an 311300 China.
RSC Adv. 2020 Feb 28;10(15):8744-8750. doi: 10.1039/d0ra00261e. eCollection 2020 Feb 27.
Graphene has been regarded as one of the most hopeful candidates for transporting drugs to target cells because of its huge surface area and high cellular uptake. In this work, we performed molecular dynamics simulations to investigate the potential application of graphene as a substrate to carry and deliver drug molecules. Bortezomib (BOR) was selected as a model drug, as its atomic structure and polarity are suitable to be adsorbed on pristine graphene (PG) and graphene oxide (GO). First, BOR molecules are loaded on graphene surface to form graphene-BOR complexes, then these complexes readily enter the lipid bilayer and finally BOR releases from graphene surface into the membrane. The entry of graphene-BOR complexes into the membrane is mainly driven by the hydrophobic interactions between lipid tails and the basal plane of nanosheets, while the electrostatic interaction between the polar groups of BOR and lipid headgroups contributes to the release of BOR from graphene into the membrane. Different from PG, BOR molecules are hard to remove from GO surface after the complex enters the lipid bilayer. The electrostatic attraction from the oxygen-containing groups enhances the binding of BOR on GO. Potential of mean force calculations confirm that BOR on GO has lower free energy than it adsorbed on PG surface. The results indicate that the adsorption intensity and release rate of graphene nanosheets can be tuned by oxidation and electrification, and graphene served as substrate to transport and release particular drug molecules is feasible.
由于石墨烯具有巨大的表面积和高细胞摄取率，它被认为是将药物输送到靶细胞的最有希望的候选者之一。在这项工作中，我们进行了分子动力学模拟，以研究石墨烯作为携带和递送药物分子的基质的潜在应用。硼替佐米（BOR）被选为模型药物，因为其原子结构和极性适合吸附在原始石墨烯（PG）和氧化石墨烯（GO）上。首先，将BOR分子负载在石墨烯表面形成石墨烯 - BOR复合物，然后这些复合物很容易进入脂质双层，最后BOR从石墨烯表面释放到膜中。石墨烯 - BOR复合物进入膜主要是由脂质尾部与纳米片基面之间的疏水相互作用驱动的，而BOR的极性基团与脂质头部基团之间的静电相互作用有助于BOR从石墨烯释放到膜中。与PG不同，复合物进入脂质双层后，BOR分子很难从GO表面去除。含氧基团的静电吸引力增强了BOR在GO上的结合。平均力势计算证实，GO上的BOR比吸附在PG表面上具有更低的自由能。结果表明，石墨烯纳米片的吸附强度和释放速率可以通过氧化和带电来调节，并且石墨烯作为输送和释放特定药物分子的基质是可行的。
