Implantable microelectrode arrays have attracted considerable interest due to their high temporal and spatial resolution recording of neuronal activity in tissues. We herein presented an implantable multichannel neural probe with multiple real-time monitoring of neural-chemical and neural-electrical signals by a nonenzymatic neural-chemical interface, which was designed by creating the newly developed reduced graphene oxide-gold oxide (rGO/Au2O3) nanocomposite electrode. The modified electrode on the neural probe was prepared by a facile one-step cyclic voltammetry (CV) electrochemical method with simultaneous occurrence of gold oxidation and GOs reduction to induce the intimate attachment by electrostatic interaction using chloride ions (Cl(-)). The rGO/Au2O3-modified electrode at a low deposition scan rate of 10 mVs(-1) displayed significantly improved electrocatalytic activity due to large active areas and well-dispersive attached rGO sheets. The in vitro amperometric response to H2O2 demonstrated a fast response of less than 5 s and a very low detection limit of 0.63 μM. In in vivo hyperacute stroke model, the concentration of H2O2 was measured as 100.48 ± 4.52 μM for rGO/Au2O3 electrode within 1 h photothrombotic stroke, which was much higher than that (71.92 μM ± 2.52 μM) for noncoated electrode via in vitro calibration. Simultaneously, the somatosensory-evoked potentials (SSEPs) test provided reliable and precise validation for detecting functional changes of neuronal activities. This newly developed implantable probe with localized rGO/Au2O3 nanocomposite electrode can serve as a rapid and reliable sensing platform for practical H2O2 detection in the brain or for other neural-chemical molecules in vivo.
Delivery efficiency with gene transfection is a pivotal point in achieving maximized therapeutic efficacy and has been an important challenge with central nervous system (CNS) diseases. In this study, neurotensin (NT, a neuro-specific peptide)-conjugated polyethylenimine (PEI)-modified reduced graphene oxide (rGO) nanoparticles with precisely controlled two-stage near-infrared (NIR)-laser photothermal treatment to enhance the ability to target neurons and achieve high gene transfection in neurons. First-stage NIR laser irradiation on the cells with nanoparticles attached on the surface can increase the permeability of the cell membrane, resulting in an apparent increase in cellular uptake compared to untreated cells. In addition, second-stage NIR laser irradiation on the cells with nanoparticles inside can further induce endo/lysosomal cavitation, which not only helps nanoparticles escape from endo/lysosomes but also prevents plasmid DNA (pDNA) from being digested by DNase I. At least double pDNA amount can be released from rGO-PEI-NT/pDNA under NIR laser trigger release compared to natural release. Moreover, in vitro differentiated PC-12 cell and in vivo mice (C57BL/6) brain transfection experiments have demonstrated the highest transfection efficiency occurring when NT modification is combined with external multi-stage stimuli-responsive NIR laser treatment. The combination of neuro-specific targeting peptide and external NIR-laser-triggered aid provides a nanoplatform for gene therapy in CNS diseases.
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