Graphene Oxide Quantum Dots-Loaded Extracellular Vesicles with Inflamed Pulp-Homing Targeting Enhance Pulp Repair in Pulpitis by Upregulating Glycolysis

Preservation of vital dental pulp under inflammatory conditions remains a persistent clinical challenge in endodontics. Successful inflamed dental pulp repair in pulpitis can extend affected tooth retention, but it also imposes greater demands on the anti-inflammatory and pro-differentiation effects of therapeutic agents. This study constructed a novel drug delivery system via loading graphene oxide quantum dots (GOQDs) into extracellular vesicles (EVs) derived from inflamed dental pulp stem cells (iDPSCs) by electroporation. Upon encapsulation by iDPSC-derived EVs, these engineered EVs loaded with GOQDs (GOEs) exhibited a homologous targeting effect, as evidenced by a 2.57-fold higher internalization efficiency in iDPSCs. At 10 μg/mL, GOEs exhibited excellent biocompatibility and a proliferative effect in iDPSCs. Furthermore, GOEs regulated energy metabolism in inflamed stem cells by modulating metabolic phenotype switching via enhancing glycolysis and restoring mitochondrial function. By activating the AMPK/mTOR pathway, GOEs can coordinate the glycolysis level and NF-κB inflammatory signaling in iDPSCs, reshape the inflammatory microenvironment, and improve inflamed dental pulp repair efficacy in vitro and in vivo. This study offered a promising energy-regulating nanomaterial for clinical inflamed dental pulp repair in pulpitis, providing a valuable alternative to enhance endodontic regenerative efficacy.