Fe3O4 nanoparticles suppress osteosarcoma via macrophage reprogramming and the MIP-1?-CCL3 axis

Background: Fe3O4 nanoparticles possess bone-targeting properties. This study investigated the anti-osteosarcoma mechanism of Fe3O4 nanoparticles by focusing on the tumor microenvironment, specifically examining their impact on macrophage activation. Objectives: To investigate their mechanism against osteosarcoma, focusing on the tumor microenvironment and specifically examining their impact on macrophage activation. Methods: The nanomaterials were characterized by electron microscopy and their release profiles were assessed both in-vitro and in-vivo. The antitumor activity of iron oxide nanoparticles (IONPs) was evaluated in osteosarcoma cell lines and mouse models by measuring tumor volume and size. Cytokine and inflammatory factor changes were analyzed using PCR-array and further validated by RT-PCR and Western blot. Results: All particles were within the size range of 11-17 nm with a normal distribution. Treatment with iron oxide nanoparticles significantly inhibited tumor cell proliferation, extended mouse survival and rescued macrophage activation in the tumor microenvironment. This mechanism is likely attributed to the reprogramming of macrophage activation and the activation of the MIP-1?/CCL3 signaling pathway. Conclusion: Fe3O4 nanoparticles effectively inhibit osteosarcoma progression by reprogramming macrophages and activating the MIP-1?/CCL3 signaling pathway, providing a new direction for developing nanotechnology-based immunotherapy strategies for osteosarcoma.