Su Guanyue, Yu Hongchi, Hong Jinyong, Wang Xiaoli, Feng Tang, Wu Jiang, Yin Hongmei, Shen Yang, Liu Xiaoheng
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
ACS Biomater Sci Eng. 2019 Apr 8;5(4):1804-1821. doi: 10.1021/acsbiomaterials.8b01648. Epub 2019 Mar 28.
Gold nanoparticles (Au NPs) have received much attention because of their distinct physicochemical properties. The surface terminal functional groups of Au NPs can facilitate easy conjugation with biological molecules for targeting cancer cells and controlling drugs/genes release. However, little is known regarding molecular mechanisms involved in their regulation of cancer cell migration and invasion. In the present study, Au NPs were successfully conjugated with functional groups (CH, NH, OH and COOH) by self-assembled monolayer (SAM) technique. The endocytosis of SAM-Au NPs mediating HepG2 cell migration and invasion in integrin-induced cascaded events were examined. Our results showed that the combination of integrins-Caveolin-1 together contributed to the internalization of SAM-Au NPs. The CH-Au NPs showed fast cell motility than COOH- and OH- groups by upregulating PI3K expression, but reducing FAK phosphorylation level. Additionally, CH-Au NPs showed the strongest activated GTP-bound Rac1 and RhoA. Taken together, these results concluded that internalization of SAM-Au NPs inhibited cancer cell migration via FAK/PI3K and downstream Rho-GTPase signaling pathway in a time-dependent manner. This work provides a further understanding of SAM-Au NPs regulating cancer cell migration, which might be helpful to functionalize the Au NP surface in drug delivery system.
金纳米颗粒（Au NPs）因其独特的物理化学性质而备受关注。Au NPs的表面末端官能团能够促进与生物分子的轻松结合，从而靶向癌细胞并控制药物/基因释放。然而，关于其调控癌细胞迁移和侵袭的分子机制却知之甚少。在本研究中，通过自组装单分子层（SAM）技术成功地将Au NPs与官能团（CH、NH、OH和COOH）进行了共轭。研究了SAM-Au NPs在整合素诱导的级联事件中介导HepG2细胞迁移和侵袭的内吞作用。我们的结果表明，整合素与小窝蛋白-1共同作用促进了SAM-Au NPs的内化。CH-Au NPs通过上调PI3K表达，但降低FAK磷酸化水平，显示出比COOH-和OH-基团更快的细胞运动性。此外，CH-Au NPs显示出最强的激活的GTP结合的Rac1和RhoA。综上所述，这些结果表明，SAM-Au NPs的内化通过FAK/PI3K和下游Rho-GTPase信号通路以时间依赖性方式抑制癌细胞迁移。这项工作进一步加深了对SAM-Au NPs调控癌细胞迁移的理解，这可能有助于在药物递送系统中对Au NP表面进行功能化。
