This study investigates the use of chondrocyte-targeted exosome-mediated delivery of Nrf2 to alleviate cartilaginous endplate (CEP) degeneration and intervertebral disc degeneration (IVDD). The researchers engineered exosomes (CAP-Nrf2-Exos) with a chondrocyte-affinity peptide (CAP) on their surface and loaded them with the antioxidant transcription factor Nrf2. These exosomes were shown to efficiently deliver Nrf2 to CEP cells, activating the endogenous antioxidant defense system and inhibiting Drp1-mediated mitochondrial fission, which is a key factor in CEP degeneration and apoptosis. The study demonstrated that CAP-Nrf2-Exos significantly reduced LPS-induced CEP cell apoptosis and improved the repair of CEP degeneration in a rat model of IVDD compared to natural exosomes. The results suggest that exosome-mediated chondrocyte-targeted delivery of Nrf2 is a promising strategy for treating CEP degeneration and IVDD. The study highlights the potential of engineered exosomes in targeting specific cells and delivering therapeutic agents to treat degenerative diseases. The findings indicate that the combination of surface modification and cargo loading can enhance the therapeutic effects of exosomes, making them a valuable tool in the treatment of intervertebral disc degeneration.This study investigates the use of chondrocyte-targeted exosome-mediated delivery of Nrf2 to alleviate cartilaginous endplate (CEP) degeneration and intervertebral disc degeneration (IVDD). The researchers engineered exosomes (CAP-Nrf2-Exos) with a chondrocyte-affinity peptide (CAP) on their surface and loaded them with the antioxidant transcription factor Nrf2. These exosomes were shown to efficiently deliver Nrf2 to CEP cells, activating the endogenous antioxidant defense system and inhibiting Drp1-mediated mitochondrial fission, which is a key factor in CEP degeneration and apoptosis. The study demonstrated that CAP-Nrf2-Exos significantly reduced LPS-induced CEP cell apoptosis and improved the repair of CEP degeneration in a rat model of IVDD compared to natural exosomes. The results suggest that exosome-mediated chondrocyte-targeted delivery of Nrf2 is a promising strategy for treating CEP degeneration and IVDD. The study highlights the potential of engineered exosomes in targeting specific cells and delivering therapeutic agents to treat degenerative diseases. The findings indicate that the combination of surface modification and cargo loading can enhance the therapeutic effects of exosomes, making them a valuable tool in the treatment of intervertebral disc degeneration.