Electromagnetic Stimulation on Magnetic Plasmonic Nanoparticles to Regulate Cellular Activities

Abstract

Neurodegenerative disorder imposes a significant challenge in neuroscience due to the lack of effective treatment to reverse the progress. Here we introduce an approach of using multifunctional superparamagnetic iron oxide (SPIO)-gold (Au) core-shell nanoparticles (NPs) to regulate cellular activities and promote neuronal differentiation and neurite growth under the stimulation of electromagnetic fields. SPIO-Au NPs were firstly synthesized by a synergistic seed growth method with tunable thicknesses, uniform quasispherical nanostructures and excellent plasmonic properties. The high stabilities of SPIOAu NPs in deionized water and cell culture medium were then confirmed by UV-Vis absorption spectra and zeta potential measurements. The outstanding plasmonic properties were further characterized by using a novel thermocouple (TC)-tip-exposing technique to measure the temperature profile of NPs with laser irradiation in a simple and accurate way. The near unity photothermal conversion efficiency (≈1) of NPs (26 nm) was demonstrated by embedding the finite element modeling with experimentally measured parameters. Then the SPIO-Au NPs were functionalized with nerve growth factor (NGF) with high stability for the magnetic fields (MFs) stimulation. The enhanced cell uptake of NPs by the bounded NGF and their high cell viability were observed in PC-12 neuron cells. The NGF-SPIO-Au NPs also showed the promotional effect on neuronal differentiation, neurite growth and orientation by the stimulation of dynamic MFs, which performed better than their static counterparts. In the end, the effect of NGF-SPIO-Au NPs on promoting the neuronal differentiation in response to light emitting diode (LED) stimulation was explored. LEDs (1.9 mW/cm2 ) exhibited no obvious cellular toxicity and no significant reduction of proliferation for up to 1 h of exposure. The promotional effect of LEDs and NGF-SPIOAu NPs on neuronal differentiation and neurite growth was proved through morphology studies. The stimulation of LEDs on NGF-SPIO-Au NPs with strong photothermal effect also triggered an increase of calcium level and the upregulation of the neuronal differentiation specific marker b3 tubulin and the cell adhesive molecule integrin b1 through the activation of plasmonic NGF-SPIO-Au NPs. To conclude, the capacities of multifunctional SPIO-Au NPs on regulating the cellular activities and promoting the neuronal differentiation suggest the strong potential of this nanomedicine for neuroregeneration.