Abstract

Oxidative stress, mitochondrial dysfunction, and autophagy imbalance form a vicious cycle driving intervertebral disc degeneration (IVDD). However, comprehensive therapeutic strategies remain limited. To address this, we engineered a biomimetic nanoparticle (NPCM@CeO 2 -RAPA) by encapsulating cerium oxide (CeO 2 ) and rapamycin (RAPA) within a nucleus pulposus cell membrane (NPCM) shell. This biomimetic encapsulation enabled precise targeting of nucleus pulposus cells through membrane fusion. In vitro studies demonstrated that while CeO 2 alone alleviated oxidative stress and partially restored mitochondrial function, and RAPA individually modulated autophagy, the combined treatment NPCM@CeO 2 -RAPA exhibited superior therapeutic effects. In vivo, the composite nanoparticle significantly suppressed catabolic activity and attenuated IVDD progression in a puncture-induced rat IVDD model. These findings highlight NPCM@(CeO 2 -RAPA) as a precise and synergistic nanotherapeutic with strong translational potential for IVDD management.