A Biomimetic Polymer Magnetic Nanocarrier Polarizing Tumor‐Associated Macrophages for Potentiating Immunotherapy

Abstract

The progress of antitumor immunotherapy is usually limited by tumor‐associated 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.

Applications of Magnetite Nanoparticles in Cancer Immunotherapies: Present Hallmarks and Future Perspectives

“…In vivo, experimental tumors were restricted in their growth by treatment with ferumoxytol and showed an increased number of M1-like infiltrating macrophages in comparison to the untreated tumors (52). Other studies also exploited MNPs for inducing M1 polarization of TAMs, as recently shown with polymeric NPs coated with a membrane of LPS treated macrophage, and encapsulating Fe 3 O 4 NPs and the imiquimod (Toll-like receptor 7 agonist, a strong macrophage activator), which were able to polarize TAMs towards M1 and achieve a concomitant restriction of experimental tumor growth (53). The membrane was prepared by the LPS stimulated macrophages to specifically target TAMs without direct M1 polarization effects that can be verified from the macrophage polarization results of PLGA-ION (PI) and membrane-coated PLGA-ION (PI@M) NPs.…”

A Redox‐Responsive Nanovaccine Combined with A2A Receptor Antagonist for Cancer Immunotherapy

“…The cytocompatibility was assessed by the qualitative analysis of calcein‐pyridine iodide and the quantitative analysis of the Alamar Blue assay. [ 20 ] Green and red fluorescence represented live cells and dead cells, respectively. As shown in Figure S9a,b, Supporting Information, regardless of 4T1 cells or human umbilical vein endothelial cells (HUVECs), it was observed under the Zeiss fluorescence microscope (FM) that the green fluorescence in RPsP with the concentrations from 25 to 400 µg mL −1 was not significantly different from the control group and the red fluorescence was not obvious, suggesting that the micelles almost had no toxicity to 4T1 cells and HUVECs.…”

Nanoparticles to Target and Treat Macrophages: The Ockham’s Concept?

“…Iron oxide NPs coated with biomimetic membranes from LPS-treated macrophages have also been designed and tested for TAM re-education in a murine model of breast cancer [115]. These NPs were decorated with a TLR7 agonist to boost the activation of NF-κB [115]. Other authors have also suggested the use of TLR7 and TLR8 agonists to induce the activation of NF-κB to enhance immunotherapy efficacy and to increase TNF-α and IL-6 secretion [129].…”

“…The transcription factor NF-κB successfully activated TAM to induce M1 polarization [ 114 ]. Iron oxide NPs coated with biomimetic membranes from LPS-treated macrophages have also been designed and tested for TAM re-education in a murine model of breast cancer [ 115 ]. These NPs were decorated with a TLR7 agonist to boost the activation of NF-κB [ 115 ].…”