Macrophage-biomimetic porous Se@SiO(2) nanocomposites for dual modal immunotherapy against inflammatory osteolysis

BACKGROUND: Inflammatory osteolysis, a major complication of total joint replacement surgery, can cause prosthesis failure and necessitate revision surgery. Macrophages are key effector immune cells in inflammatory responses, but excessive M1-polarization of dysfunctional macrophages leads to the secretion of proinflammatory cytokines and severe loss of bone tissue. Here, we report the development of macrophage-biomimetic porous SiO(2)-coated ultrasmall Se particles (porous Se@SiO(2) nanospheres) to manage inflammatory osteolysis. RESULTS: Macrophage membrane-coated porous Se@SiO(2) nanospheres(M-Se@SiO(2)) attenuated lipopolysaccharide (LPS)-induced inflammatory osteolysis via a dual-immunomodulatory effect. As macrophage membrane decoys, these nanoparticles reduced endotoxin levels and neutralized proinflammatory cytokines. Moreover, the release of Se could induce macrophage polarization toward the anti-inflammatory M2-phenotype. These effects were mediated via the inhibition of p65, p38, and extracellular signal-regulated kinase (ERK) signaling. Additionally, the immune environment created by M-Se@SiO(2) reduced the inhibition of osteogenic differentiation caused by proinflammation cytokines, as confirmed through in vitro and in vivo experiments. CONCLUSION: Our findings suggest that M-Se@SiO(2) have an immunomodulatory role in LPS-induced inflammation and bone remodeling, which demonstrates that M-Se@SiO(2) are a promising engineered nanoplatform for the treatment of osteolysis occurring after arthroplasty. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-01128-4.