Orchestrated Yolk-Shell Nanohybrids Regulate Macrophage Polarization and Dendritic Cell Maturation for Oncotherapy with Augmented Antitumor Immunity.

The protumoral and immunosuppressive tumor microenvironments greatly limit the antitumor immune responses of nanoparticles for cancer immunotherapy. Here, the intrinsic immunomodulatory effects of orchestrated nanoparticles and their ability to simultaneously trigger tumor antigen release, thereby reversing immunosuppression and achieving potent antitumor immunity and augmented cancer therapy, are explored. By optimizing both the composition and morphology, a facile strategy is proposed to construct yolk-shell nanohybrids (Fe3 O4 @C/MnO2 -PGEA, FCMP). The intrinsic immunomodulatory effects of FCMP are utilized to reprogram macrophages to M1 phenotype and induce the maturation of dendritic cells. In addition, the chemical, magnetic, and optical properties of FCMP contribute to amplified immunogenic cell death induced by multiaugmented chemodynamic therapy (CDT) and synergistic tumor treatment. Taking advantage of the unique yolk-shell structure, accurate T1 -T2 dual-mode magnetic resonance imaging can be realized and CDT can be maximized through sufficient exposure of both the Fe3 O4 core and MnO2 shell. Potent antitumor effects are found to substantially inhibit the growth of both primary and distant tumors. Furthermore, the strategy can be extended to the synthesis of other yolk-shell nanohybrids with tailored properties. This work establishes a novel strategy for the fabrication of multifunctional nanoplatforms with yolk-shell structure for effective cancer therapy with immunomodulation-enhanced antitumor immunity.