A Se Nanoparticle/MgFe‐LDH Composite Nanosheet as a Multifunctional Platform for Osteosarcoma Eradication, Antibacterial and Bone Reconstruction

Abstract Despite advances in treating osteosarcoma, postoperative tumor recurrence, periprosthetic infection, and critical bone defects remain critical concerns. Herein, the growth of selenium nanoparticles (SeNPs) onto MgFe‐LDH nanosheets (LDH) is reported to develop a multifunctional nanocomposite (LDH/Se) and further modification of the nanocomposite on a bioactive glass scaffold (BGS) to obtain a versatile platform (BGS@LDH/Se) for comprehensive postoperative osteosarcoma management. The uniform dispersion of negatively charged SeNPs on the LDH surface restrains toxicity‐inducing aggregation and inactivation, thus enhancing superoxide dismutase (SOD) activation and superoxide anion radical (·O 2 − )‐H 2 O 2 conversion. Meanwhile, Fe 3+ within the LDH nanosheets can be reduced to Fe 2+ by depleting glutathione (GSH) in the tumor microenvironments (TME), which can catalyze H 2 O 2 into highly toxic reactive oxygen species. More importantly, incorporating SeNPs significantly promotes the anti‐bacterial and osteogenic properties of BGS@LDH/Se. Thus, the developed BGS@LDH/Se platform can simultaneously inhibit tumor recurrence and periprosthetic infection as well as promote bone regeneration, thus holding great potential for postoperative “one‐stop‐shop” management of patients who need osteosarcoma resection and scaffold implantation.