Electrochemical Control of Neuroblastoma Differentiation Based on Nanostructured Biohybrid Material

Abstract

Because of its high applicability to regenerative medicine and stem-cell therapy, accurate control of the neural differentiation has attracted lots of attention in the neurobiological field. For this reason, the introduction of nanoparticles or nanopatterned electrode for the induction of accurate neural differentiation has been reported by various researchers. However, these materials still have limitations such as cytotoxicity effects caused by nanoparticles and low specificity and efficiency of differentiation. Therefore, it is essential to develop a new method of inducing neural differentiation with high biocompatibility and specificity to solve the above-mentioned shortcomings. In this study, for the first time, the nanostructured biohybrid material composed of recombinant azurin (Azu), DNA, and gold nanoparticle (AuNP) for the neural differentiation with high biocompatibility and specificity was developed. Due to the introduction of biomaterials such as Azu and DNA, the nanostructured biohybrid material showed high biocompatibility. Furthermore, electrically controllable complex with the differentiation inducible agent allowed by introduced AuNP connected to the nanostructured biohybrid material without the chemical linker. The result showed that the neural differentiation was successfully conducted by the release of the differentiation inducible agent from an electrically controllable complex with electrochemical control. Moreover, it was possible to spatiotemporal control of the neural differentiation over a long period by adjusting the time and location of applying electrical stimulation. In conclusion, the developed nanostructured biohybrid material can be applied as a novel platform that can effectively differentiate stem cells into the desired type of differentiated cells for regenerative medicine and stem cell therapy.