Graphene oxide (GO) has been extensively explored in nanomedicine for its excellent physiochemical, electrical, and optical properties. Here, polyethylene glycol (PEG) and polyethylenimine (PEI) are covalently conjugated to GO via amide bonds, obtaining a physiologically stable dual-polymer-functionalized nano-GO conjugate (NGO-PEG-PEI) with ultra-small size. Compared with free PEI and the GO-PEI conjugate without PEGylation, NGO-PEG-PEI shows superior gene transfection efficiency without serum interference, as well as reduced cytotoxicity. Utilizing the NIR optical absorbance of NGO, the cellular uptake of NGO-PEG-PEI is shown to be enhanced under a low power NIR laser irradiation, owing to the mild photothermal heating that increases the cell membrane permeability without significantly damaging cells. As the results, remarkably enhanced plasmid DNA transfection efficiencies induced by the NIR laser are achieved using NGO-PEG-PEI as the light-responsive gene carrier. More importantly, it is shown that our NGO-PEG-PEI is able to deliver small interfering RNA (siRNA) into cells under the control of NIR light, resulting in obvious down-regulation of the target gene, Polo-like kinase 1 (Plk1), in the presence of laser irradiation. This study is the first to use photothermally enhanced intracellular trafficking of nanocarriers for light-controllable gene delivery. This work also encourages further explorations of functionalized nano-GO as a photocontrollable nanovector for combined photothermal and gene therapies.
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