Iron Oxyhydroxide Nanorods Coated with Poly(acrylic acid) to Reprogram Tumor-Associated Macrophages for Antitumor Immunotherapy

Tumor-associated macrophages (TAMs) are vital in regulating the immunosuppressive tumor microenvironment (TME). Reprogramming TAMs from M2 to M1 phenotype can remodel TME from causing immunosuppression to immunostimulation. The establishment of a property–activity relationship between the size of iron-based nanomaterials and TAM polarization is beneficial for the design of efficient antitumor immunoreagents. In the present study, various iron oxyhydroxide (FeOOH) nanorods (NRs) with similar aspect ratios but different sizes were prepared and coated with poly(acrylic acid) (PAA) to form PFeOOH NRs. A size-dependent reprogramming ability was revealed in PFeOOH NRs, which was ascribed to their iron dissolution and cell uptake. Furthermore, PFeOOH NRs were loaded with doxorubicin (DOX) to DPFeOOH NRs for the exploration of antitumor immune response stimulation through TAM reprogramming and immunogenic cell death (ICD). The results indicated the enhanced antitumor performance of DPFeOOH NRs compared with PFeOOH NRs and DOX. This study reveals the underlying mechanism of PFeOOH NRs in TAM reprogramming and exhibits the potent immunotherapeutic effect of DPFeOOH NRs.