Department of Chemistry and Forensic Science, Albany State University, Albany, GA 31705, USA.
Phys Chem Chem Phys. 2018 Apr 4;20(14):9389-9400. doi: 10.1039/C8CP00124C.
Two widely used anticancer drugs, doxorubicin (DOX) and paclitaxel (PTX), possess distinct physical properties and chemotherapy specificity. In order to investigate their interaction mechanism with single-walled carbon nanotubes (SWCNTs), co-loading and releasing from the SWCNTs, all-atom molecular dynamics (MD) simulations were firstly carried out for different SWCNT systems, followed by binding free energy calculation with MM-PBSA. The results indicate that the co-loading of DOX and PTX onto the pristine SWCNT is exothermic and spontaneous. The DOX molecules predominantly interact with the SWCNT via π-π stacking through the conjugated aromatic rings, while the separated aromatic rings of PTX also primarily interact with the SWCNT through π-π stacking yet supplemented by an X-π (X = C-H, N-H and C[double bond, length as m-dash]O) interaction. Moreover, the strongest binding of DOX and PTX with the pristine SWCNT shows similar strength (ΔG: -32.0 vs. -33.8 kcal mol-1). For the chitosan functionalized SWCNT (f-SWCNT), the DOX and PTX molecules still prefer binding to the sidewall of the CNT rather than binding with the polymer, and the non-covalent functionalization of the SWCNT with chitosan decreases the binding of DOX and PTX with the sidewall of the f-SWCNT as compared with the DOX/PTX-SWCNT system (ΔG: -24.0 and -21.9 kcal mol-1). The protonation of chitosan and drug molecules further weakens the interaction between DOX/PTX and the f-SWCNT, and shows a consequent displacement of the drug molecules, triggering the release of the drugs. The variation of binding strength of the three systems (DOX/PTX-SWCNT, DOX/PTX-f-SWCNT, and DOXH+/PTXH+-f-SWCNT) was also discussed in terms of the histogram or frequency of the distance from the drugs to the SWCNT. In addition, the encapsulation of two DOX molecules by the f-SWCNT is considerably stronger than the binding of the other six drug molecules to the sidewall, indicating that the encapsulation of anticancer drugs may also play a very important role and should be considered in the drug delivery.
两种广泛使用的抗癌药物，阿霉素（DOX）和紫杉醇（PTX），具有不同的物理性质和化疗特异性。为了研究它们与单壁碳纳米管（SWCNT）的相互作用机制，包括从 SWCNT 上的共加载和释放，首先对不同的 SWCNT 系统进行了全原子分子动力学（MD）模拟，然后通过 MM-PBSA 计算结合自由能。结果表明，DOX 和 PTX 共加载到原始 SWCNT 上是放热和自发的。DOX 分子主要通过共轭芳环的π-π堆积与 SWCNT 相互作用，而 PTX 的分离芳环也主要通过π-π堆积与 SWCNT 相互作用，但辅以 X-π（X = C-H、N-H 和 C[双键，长度为 m-dash]O）相互作用。此外，DOX 和 PTX 与原始 SWCNT 的最强结合表现出相似的强度（ΔG：-32.0 与-33.8 kcal mol-1）。对于壳聚糖功能化的 SWCNT（f-SWCNT），DOX 和 PTX 分子仍然更喜欢与 CNT 的侧壁结合，而不是与聚合物结合，并且 SWCNT 与壳聚糖的非共价功能化与 DOX/PTX-SWCNT 系统相比降低了 DOX 和 PTX 与 f-SWCNT 侧壁的结合（ΔG：-24.0 和-21.9 kcal mol-1）。壳聚糖和药物分子的质子化进一步削弱了 DOX/PTX 与 f-SWCNT 的相互作用，并导致药物分子的位移，触发药物的释放。还讨论了三个系统（DOX/PTX-SWCNT、DOX/PTX-f-SWCNT 和 DOXH+/PTXH+-f-SWCNT）的结合强度变化，包括药物与 SWCNT 的距离直方图或频率。此外，f-SWCNT 中两个 DOX 分子的封装强度明显强于其他六个药物分子与侧壁的结合，表明抗癌药物的封装也可能发挥非常重要的作用，在药物输送中应予以考虑。
