Macrophages loaded with dendrimer-entrapped gold nanoparticles as a theranostic platform for CT imaging-guided combinational therapy of orthotopic osteosarcoma

•The novel engineered macrophages as a theranostic platform are developed.•Au DENPs can polarize macrophages into the M1-like phenotype.•The engineered macrophages can enhance CT imaging of the orthotopic osteosarcoma.•Au DENPs@Macs can be used as an effective theranostic platform for osteosarcoma. Immune cell therapy has recently emerged as a promising treatment modality for malignant tumors. Specifically, nanoparticle-mediated cell-immunotherapy has attracted considerable attention due to the combined contributions of the biological regulation of nanoparticles and the intrinsic nature of immune cells. Herein, engineered macrophages with dendrimer-entrapped gold nanoparticles (Au DENPs@Macs) were designed as a theranostic cell platform, for the first time, for CT imaging-guided cell immunotherapy and chemotherapy of osteosarcoma. In this study, Au DENPs were synthesized and used to activate macrophages into the anti-tumorigenic M1-like phenotype, characterized by the increased expression of CD86, the inducible type of nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF-α). After loading Au DENPs, the engineered macrophages showed cytostatic/pro-apoptotic effects against cancer cells and achieved CT imaging performance in vitro and in vivo. The combination of cell therapy and chemotherapy demonstrated a cooperative impact in enhancing cancer treatment. Our findings reveal that Au DENPs@Macs can be used as a theranostic platform for osteosarcoma, which may present a brand‐new strategy for immune cell-combined chemotherapy of other cancer types.