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2.3.2 Toll-like receptor agonists TLR agonists (including TLR7 agonists, TLR-7/8 agonists, and TLR9 agonists) can also polarize M2-like TAMs to M1-like TAMs in addition to iron-based nanoparticles, but their application in vivo is limited by the fact that TLRs are easily cleared by nucleases in circulation and can also trigger inflammatory responses through non-specific stimulation (20), while the TLR loaded inside the nanoparticle not only protects the TLR from the effects of nucleases in the blood, reduces the systemic side effects caused by TLR agonists, but also enables them to target TAMs to exert their effects, such as the nanoparticles Poly(L-lactic-co-glycolic acid) (PLGA)- ION-R837@M (PIR@M) formed by the magnetic polymer nanoparticles encapsulated with Fe 3 O 4 NPs and the TLR7 agonist imiquimod (R837) coated with lipopolysaccharide (LPS)-treated macrophage membranes can target TAMs, in which PIR@M can polarize TAMs from M2 to an anti-tumor M1 phenotype by the synergistic effect of Fe 3 O 4 NPs and R837 thereby attenuating immunosuppressive TME and activating the anti-tumor immune response (39)

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The study reported that the CoEQ was used on an item-by-item basis in previous pharmaceutical weight loss trials