Itaconate-loaded metal–organic framework (MOF) nanomedicine for the sustained treatment of intervertebral disk degeneration

Intervertebral disk degeneration (IVDD) is a major cause of spinal pathology and pain and can lead to disability in adults in severe cases. The medication against disk degeneration is limited due to the lack of therapeutic drugs and ineffective delivery of molecular drugs to target microenvironment. Itaconate is a tricarboxylic acid cycle secondary metabolite with inflammatory and oxidative stress modulating functions, which could alleviate disk degeneration. However, the lack of in vivo stability limits the potential application of itaconate against disk degeneration. In this study, we prepared metal–organic framework (MOF) nanocarrier drug loaded with itaconate that can respond to the acidic environment during disk degeneration. The results showed that the acidic microenvironment could induce sustained drug release from MOF@itaconate. In vitro cellular evaluation showed that MOF@itaconate has good cytocompatibility and significantly attenuates the inflammatory injury of nucleus pulposus cells. The nanocarrier activates the nuclear factor erythroid 2-related factor 2 (Nrf 2) anti-oxidative pathway and promotes the expression of nucleus pulposus extracellular matrix components. For the treatment of intervertebral disk degeneration on animal models, the MOF@itaconate nanocarrier was further coated with hyaluronic acid (HA) to boost the therapeutic effect. The administration of MOF@itaconate@HA in a rat disk degeneration model effectively delayed the degenerative process, suggesting that this technology may provide an effective controlled-release strategy for the treatment of IVDD.