Molecular simulation on doxorubicin encapsulation and transport by chitosan-boron nitride nanotubes

doi:10.11949/0438-1157.20191226

Abstract

Abstract:

There is a potential application prospect of chitosan BNNTs composite carrier in the field of drug transport. It is important to understand the mechanism of the encapsulation and transport of drugs by chitosan-BNNTs from atomic level. Herein, molecular dynamics (MD) simulation was employed to investigate the process of encapsulation and transmembrane delivery of doxorubicin (DOX) by chitosan-BNNTs. The anticancer drug DOX was used as a drug model. The free energy results indicate that DOX and chitosan can spontaneously enter the tube. It is also found that DOX can be adsorbed by the non-protonated chitosan and enter the tube in a suitable conformation. The interaction energy results show that phospholipid molecules can embed into BNNT (14,14) tubes, and extrude chitosan and DOX in the tube. This study can provide ideas for experiments to improve drug encapsulation efficiency and increase drug concentration on cancer cells.

Key words: chitosan, cell membrane, nanotube, drug

摘要：

壳聚糖-BNNTs复合载体在药物输运领域存在潜在的应用前景。通过分子动力学方法，以抗癌药物阿霉素DOX为药物模型，研究利用壳聚糖-BNNTs复合载体材料封装及跨膜输运抗癌药物的过程。结果表明，非质子化壳聚糖能吸附且调整DOX以合适的构象进入管中。细胞膜磷脂分子能自发嵌入到BNNT (14,14)管中，将管中壳聚糖挤出并使DOX在管中快速上升。该研究可以为实验提高药物封装效率，并提高癌细胞表面药物浓度提供设计思路。

关键词: 壳聚糖, 细胞膜, 纳米管, 药物

CLC Number:

O 641.3

Jiachen LI, Bin YU, Qi WANG, Li ZHANG. Molecular simulation on doxorubicin encapsulation and transport by chitosan-boron nitride nanotubes[J]. CIESC Journal, 2020, 71(1): 354-360.

李嘉辰, 俞斌, 王琦, 张丽. 分子模拟研究壳聚糖-氮化硼纳米管封装及输运阿霉素[J]. 化工学报, 2020, 71(1): 354-360.

Figures/Tables 7

Fig.1 Initial structure of chitosan with 10 units was generated by replacing glucose unit —OH group into —NH2 and —NH3+ groups, respectively

Fig.2 Initial structure of encapsulation(a) and transmembrane transport(b) of DOX by chitosan-BNNT (14,14)

Fig.3 (a) Center of mass (COM) distance between CS_A10/DOX and BNNT (14,14) versus simulation time; (b) snapshot of system at 0 and 30 ns

Fig.4 Potential of mean force (PMF) of —NH2 and DOX passing through BNNT (14,14) [The reaction coordinate is along the central axis of BNNTs. 0 nm is the middle location of the tube and the dotted lines represent the end location of BNNT (14,14)]

Fig.5 (a) Ⅰ: Density map of water molecules in BNNT (14,14) in xy plane; DOX with different orientations in xy plane, Ⅱ: vertical; Ⅲ: horizontal; (b) external force on DOX versus simulation time [the pull rate is 0.01 nm/ps and the dotted lines represent the end location of BNNT (14,14)]

Fig.6 Snapshot of transmembrane transport of DOX by chitosan-BNNT (14,14)

Fig.7 (a) COM distance between POPC/CS_B10/DOX and BNNT (14,14) versus simulation time; (b) interaction energy between CS_B10/DOX/PO and BNNT (14,14); (c) snapshot in BNNT (14,14) (the dotted line is the center of POPC)

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