Carbon Dot-Engineered Graphene Oxide-Silver Nanoparticle Nanocomposites Orchestrate Conductivity-Redox Coupling for Neuronal Regeneration.

Oxidative stress-induced disruption of neuronal signaling remains a central barrier in the treatment of neurological disorders, where excessive reactive oxygen species (ROS) compromise ion channel function, synaptic transmission, and neuronal differentiation. Although conductive nanomaterials such as graphene oxide-silver nanoparticles (GO-AgNPs) have shown promise in promoting neurite outgrowth and neuronal maturation, their application is limited by structural instability and burst silver ion (Ag+) release under oxidative conditions. Here, we introduce a carbon dot (CD)-enabled strategy to stabilize conductive GO-Ag nanocomposites via green, in situ integration of folic acid-derived nitrogen-doped CDs. This design transforms conventional GO-AgNPs into a redox-active, self-regulating conductive platform, GO-CD-AgNPs (GC-AgNPs), that simultaneously enhances electrical stability and mitigates oxidative damage. GC-AgNPs exhibit sustained electrical conductivity under oxidative stress and markedly enhanced radical scavenging capacity. In SH-SY5Y cells, GC-AgNPs significantly reduce cytotoxicity by preventing superoxide overproduction and intracellular Ca2+ overload. Under oxidative stress, these nanocomposites promote neuronal maturation, as evidenced by increased expression of MAP2 and NF-H. In addition, GC-AgNPs suppress pro-inflammatory cytokine secretion in HMC3 microglia, demonstrating concurrent immunomodulatory effects. Collectively, by resolving the intrinsic coupling between conductivity and oxidative stability, this work establishes a design framework for redox-adaptive conductive biomaterials. This strategy provides a promising approach for designing electroactive biomaterials capable of maintaining neural network integrity in challenging pathological microenvironments.