Tumor-associated macrophages (TAMs) that infiltrate in most tumor tissues are closely correlated with proliferation and metastasis of tumor cells. Immunomodulation of TAMs from pro-tumorigenic M2 phenotype to anti-tumorigenic M1 phenotype is crucial for oncotherapy. Herein, an iron nanotrap was utilized to remodel TAMs for tumor growth inhibition. In the formulation, the ultrasmall nanotrap could capture and targetedly transport endogenous iron into TAMs even inside the tumor. Upon exposing to the lysosomal acidic conditions and intracellular H2O2, iron was released from the nanotrap and produced the generation of oxidative stress, which could reprogram TAMs. The activated M1 macrophages could induce immune responses and suppress tumor growth ultimately. Meanwhile, this metal-free nanotrap with degradability by H2O2 possessed favorable biocompatibility. Our work would present potential opportunities of utilizing endogenous substances for secure treatment of various diseases.
Keywords: endogenous iron; immunotherapy; nanotrap; repolarization; tumor-associated macrophages.