Engineering magnetosomes for ferroptosis/immunomodulation synergism in cancer

Abstract

As traditional anticancer treatments fail to significantly improve the prognoses, exploration of therapeutic modalities is urgently needed. Herein, a biomimetic magnetosome is constructed to favor the ferroptosis/immunomodulation synergism in cancer. This magnetosome is composed of an Fe3O4 magnetic nanocluster (NC) as the core and pre-engineered leukocyte membranes as the cloak, wherein TGF-β inhibitor (Ti) can be loaded inside the membrane and PD-1 antibody (Pa) can be anchored on the membrane surface. After intravenous injection, the membrane camouflage results in long circulation, and the NC core with magnetization and superparamagnetism enables magnetic targeting with magnetic resonance imaging (MRI) guidance. Once inside the tumor, Pa and Ti cooperate to create an immunogenic microenvironment, which increases the amount of H2O2 in polarized M1 macrophages and thus promotes the Fenton reaction with Fe ions released from NCs. The generated hydroxyl radicals (•OH) subsequently induce lethal ferroptosis to tumor cells, and the exposed tumor antigen, in turn, improves the microenvironment immunogenicity. The synergism of immunomodulation and ferroptosis in such a cyclical manner therefore leads to potent therapeutic effects with few abnormalities, which supports the engineered magnetosomes as a promising combination modality for anticancer therapy.