Enhancing Bone Regeneration through CDC20‐Loaded ZIF‐8 Nanoparticles Wrapped in Erythrocyte Membranes with Targeting Aptamer

Abstract In the context of bone regeneration, nanoparticles harboring osteogenic factors have emerged as pivotal agents for modulating the differentiation fate of stem cells. However, persistent challenges surrounding biocompatibility, loading efficiency, and precise targeting ability warrant innovative solution. In this study, a novel nanoparticle platform founded upon the zeolitic imidazolate framework‐8 (ZIF‐8) is introduced. This new design, CDC20@ZIF‐8@eM‐Apt, involves the envelopment of ZIF‐8 within an erythrocyte membrane (eM) cloak, and is coupled with a targeting aptamer. ZIF‐8, distinguished by its porosity, biocompatibility, and robust cargo transport capabilities, constitutes the core framework. Cell division cycle protein 20 homolog (CDC20) is illuminated as a new target in bone regeneration. The eM plays a dual role in maintaining nanoparticle stability and facilitating fusion with target cell membranes, while the aptamer orchestrates the specific recruitment of bone marrow mesenchymal stem cells (BMSCs) within bone defect sites. Significantly, CDC20@ZIF‐8@eM‐Apt amplifies osteogenic differentiation of BMSCs via the inhibition of NF‐κB p65, and concurrently catalyzes bone regeneration in two bone defect models. Consequently, CDC20@ZIF‐8@eM‐Apt introduces a pioneering strategy for tackling bone defects and associated maladies, opening novel avenues in therapeutic intervention.