Electroconductive Carbon Dot/CNT-Reinforced Nanocomposite Hydrogels for Sequential Dual-Cargo Delivery with Neuronal-Cell Compatibility

We report a conductive semi-interpenetrating polymer network (semi-IPN) hydrogel reinforced with fluorescent carbon quantum dots (CDs) hydrothermally synthesized from branched polyethyleneimine and sodium alginate, together with oxidized carbon nanotubes (ox-CNTs), engineered for sequential dual-cargo delivery with pH-responsive release behavior. The hybrid matrix integrates PEDOT:PSS with a poly(acrylamide-co-2-aminoethylmethacrylate hydrochloride) network to form a robust soft material capable of sequentially releasing a neurotrophic protein and a small-molecule therapeutic. UV-visible deconvolution analysis suggested an apparent delayed release profile for glial cell line-derived neurotrophic factor (GDNF) compared with vitamin B12, which may be associated with matrix-cargo interactions within the hydrogel network. The hydrogel exhibits stable swelling behavior, mechanical integrity under physiological conditions, and tunable electrical percolation as a function of ox-CNT loading. Nanofiller incorporation through CDs enhances interfacial interactions, while ox-CNTs establish conductive pathways within the polymer network, enabling control over drug-matrix interactions and release kinetics. In vitro evaluation using MTT assays, DCFH-DA intracellular reactive oxygen species (ROS) analysis, and immunostaining of the neuronal-associated markers βIII-tubulin and MAP2 demonstrated compatibility with HT22 cells, maintenance of neuronal-associated marker expression, and reduced intracellular ROS levels under oxidative-stress conditions. Complementary molecular dynamics simulations provide qualitative molecular-level insight into the intermolecular interactions and conformational changes contributing to hybrid network stabilization. These findings demonstrate the multifunctional performance of the conductive hydrogel and support its further evaluation in advanced neuronal and in vivo models for potential applications in neural tissue engineering, soft bioelectronics, and controlled therapeutic delivery.