The progress of antitumor immunotherapy is usually limited by tumorassociated
macrophages (TAMs) that account for the highest proportion of
immunosuppressive cells in the tumor microenvironment, and the TAMs can
also be reversed by modulating the M2-like phenotype. Herein, a biomimetic
polymer magnetic nanocarrier is developed with selectively targeting and
polarizing TAMs for potentiating immunotherapy of breast cancer. This nanocarrier
PLGA-ION-R837 @ M (PIR @ M) is achieved, first, by the fabrication of
magnetic polymer nanoparticles (NPs) encapsulating Fe3O4 NPs and Toll-like
receptor 7 (TLR7) agonist imiquimod (R837) and, second, by the coating of
the lipopolysaccharide (LPS)- treated macrophage membranes on the surface
of the NPs for targeting TAMs. The intracellular uptake of the PIR @ M can
greatly polarize TAMs from M2 to antitumor M1 phenotype with the synergy
of Fe3O4 NPs and R837. The relevant mechanism of the polarization is deeply
studied through analyzing the mRNA expression of the signaling pathways.
Different from previous reports, the polarization is ascribed to the fact that
Fe3O4 NPs mainly activate the IRF5 signaling pathway via iron ions instead of
the reactive oxygen species-induced NF-κB signaling pathway. The anticancer
effect can be effectively enhanced through potentiating immunotherapy by
the polarization of the TAMs in the combination of Fe3O4 NPs and R837.


Lingqiao Liu,Yi Wang,Xing Guo,Jingya Zhao,Shaobing Zhou.