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Engineered Senescence-Targeting Apoptotic Extracellular Vesicles-Laden Injectable Hydrogel Microspheres Mitigating Nucleus Pulposus Cell Ferroptosis against Intervertebral Disc Degeneration

ABSTRACT: As the rapid growth of aging population, intervertebral disc degeneration (IVDD) becomes a prevalent degenerative disorder in clinical practice. Ferroptosis-induced senescence in nucleus pulposus cells (NPCs) represents a primary pathological mechanism underlying IVDD. Strategies for reducing ferroptosis to delay NPC senescence hold prospects for therapeutic advances. According to previously reported proteomic profiles of ApoEVs, we noticed that most key ferroptosis-regulating proteins were identified in the ApoEVs proteome, including a marked upregulation of GPX4. In this study, we developed injectable hydrogel microspheres integrating with senescent NPC-targeting apoptotic extracellular vesicles (ApoEVs) as GPX4 delivery vehicle and anti-inflammatory diclofenac sodium (DFS) for IVDD treatment. The effect of ApoEVs on reducing NPC ferroptosis and reversing NPC senescence-related metabolic dysfunction and damage was reinforced through modification of reactive oxygen species responsive and senescent NPC-targeting peptide. In vivo experiments and single cell RNA sequencing analysis elucidated that the senescence-targeted system significantly inhibited ferroptosis and inflammatory pathways, and preventedthe transformation of inflammatory NPC phenotypes, thereby offering opportunitiesfor rescuing senescent NPCs from ferroptosis and mitigating IVDD progression.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE312472 | GEO | 2026/05/01

REPOSITORIES: GEO

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