Triggered ROS cyclic responsive silicon nanowire arrays for gene transfection of stem cells

The central challenge in gene delivery systems lies in achieving efficient intracellular delivery of plasmids and sustained release. In this study, a cyclic reactive oxygen species (ROS)-responsive gene delivery platform based on silicon nanowire arrays (SN) was developed. The high-density positive charged polyethylenimine (PEI) polymers were covalently grafted onto the SN surface, allowing for electrostatic adsorption of both plasmid DNA and trans-cinnamaldehyde precursor (TAC). When cells are co-cultured on this material, the needle-like nanostructures of SN would penetrate the cell membrane through physical effect, efficiently delivering the loaded plasmids into stem cells. The release mechanism of this system was based on an ROS-triggered cascade response, TAC oxidized by ROS to generate cinnamaldehyde, and then induced mitochondrial oxidative stress to promote cascade production of more ROS. This triggered the dissociation of SN-grafted PEI from the nanowires, enabling sustained plasmid release. In vitro release assays showed that the treatment of 1 mM H 2 O 2 (exogenous ROS stimulant) for only 10 min induced 79 % plasmid release from SN surfaces. For cells that are difficult to be transfected, such as mouse embryonic stem cells (mESC) and mesenchymal stem cells (MSC), this platform exhibited excellent transfection efficiencies of 94 % and 74 %, respectively, while maintaining good cytocompatibility. This study developed an SN-based ROS-responsive gene delivery platform, achieving efficient plasmid delivery and sustained release via synergistic physical penetration and biochemical-responsiveness. It provides a solution with important application value for gene transfection in hard-to-transfect stem cells and demonstrates promising translational potential in the fields of gene therapy and regenerative medicine.