This article reports nerve growth factor functionalized superparamagnetic iron oxide?gold core-shell nanoparticles (NGF-SPIO-Au NPs), an engineered nanomedicine for non-invasive neuron regeneration when irradiated by a low-intensity light-emitting diode (LED). NGF-SPIO-Au NPs of 20 ?g/ml, were tested on PC-12 neuron-like cells, irradiated by LEDs (525 nm, 1.09, 1.44, and 1.90 mW/cm2). A remarkable Ca<
sup>
2+<
/sup>
influx was detected in differentiated PC-12 cells treated with NPs, irradiated by LED of 1.90 and 1.44 mW/cm<
sup>
2<
/sup>
with great cell viability (>
84%) and proliferations. The strong heat generated through their plasmonic surface upon LED irradiation on NGF-SPIO-Au NPs was observed. For cells treated with LED (1.90 mW/cm<
sup>
2<
/sup>
) and NGF-SPIO-Au NPs, a dramatic enhancement of neuronal differentiation (83%) and neurite outgrowth (51%) was found, and the upregulation of both the neural differentiation specific marker (?3-tubulin) and the cell adhesive molecule (integrin ?1) was observed by the reverse transcription-polymerase chain reaction and western blot analysis.