Dual Pathway for Promotion of Stem Cell Neural Differentiation Mediated by Gold Nanocomposites
Sixuan Zhang1, Yingjie Hang1, Jingxian Wu1, Zengchao Tang2, Xin Li3, Shenghan Zhang1, Lei Wang1,*（王蕾）, John L. Brash4, and Hong Chen1,*（陈红）
1State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, P. R. China
2Jiangsu Biosurf Biotech Company, Ltd., Suzhou 215123, P. R. China
3Suzhou Seemine-Nebula Biotech Company, Ltd., Suzhou 215123, P. R. China
4 School of Biomedical Engineering and Department of Chemical Engineering, McMaster University, Hamilton, Ontario L8S4L7, Canada
ACS Appl. Mater. Interfaces 2020, 12, 22066--22073
The neural differentiation of embryonic stem cells (ESCs) is of great value in the treatment of neurodegenerative diseases. On the basis of the two related signaling pathways that direct the neural differentiation of ESCs, we used gold nanoparticles (GNP) as a means of combining chemical and physical cues to trigger the neurogenic differentiation of stem cells. Neural differentiation-related functional units (glyco and sulfonate units on glycosaminoglycans, GAG) were anchored on the GNP surface and were then transferred to the cell membrane surface via GNP-membrane interactions. The functional units were able to activate the GAG-related signaling pathway, in turn promoting differentiation and maturation of stem cells into neuronal lineages. In addition, using the photothermal effect of GNP, the differentiation-inducing factor retinoic acid (RA), could be actively delivered into cells via laser irradiation. The RA-related intracellular signaling pathway was thereby further triggered, resulting in strong promotion of neurogenesis with a 300-fold increase in mature neural marker expression. The gold nanocomposites developed in this work provide the basis for a new strategy directing ESCs differentiation into nerve cells with high efficiency and high purity by acting on two related signaling pathways.