Single-Layered MoS2-PEI-PEG Nanocomposite-Mediated Gene Delivery Controlled by Photo and Redox Stimuli

Stimuli-responsive gene delivery systems maximize therapeutic efficacy by controlling the cytosolic conveyance and rate of effective gene release. We present herein a hybrid nanocomposite composed of a 2D nanomaterial, MoS2, modified by attaching two polymers (polyethylenimine (PEI) and polyethylenglycol (PEG)) via disulfide bonds. This MoS2-PEI-PEG nanocomposite interacts with DNA by electrostatic interaction, and accordingly forms a nanosized complex with high stability. Photothermal conversion of MoS2 nanosheet is employed in order to induce photothermally triggered endosomal escape upon the near infrared light irradiation. After endosomal escape, polymers are detached from the MoS2 nanosheet by the intracellular reducing agent, glutathione (GSH), resulting in effective gene release from the nanocomposite. This sequential process initiated by external and internal stimuli remarkably enhances gene delivery efficiency by effective endosomal escape and gene release without severe cytotoxicity. Our rationally designed MoS2 nanocomposite provides a spatiotemporally controllable platform to deliver genetic material into cells.