M1/M2 re-polarization of kaempferol biomimetic NPs in anti-inflammatory therapy of atherosclerosis

Atherosclerosis (AS), a leading cause of death worldwide, involves chronic macrophage inflammation from its initiation to the emergence of complications. Targeting plaque inflammation by re-polarizing pro-inflammatory M1 to anti-inflammatory M2 could therefore provide a promising strategy to treat AS, but currently available anti-inflammatory drugs limit clinical outcomes. In this study, we found that kaempferol (KPF) is capable of potential anti-inflammation as a novel drug candidate, which has been scarcely reported. Building upon these findings, we fabricated a macrophage-biomimetic KPF delivery platform, abbreviated as KPF@MM-NPs to potentiate therapeutic payloads, wherein the designed ROS-responsive Dextran-g-PBMEO NPs with π-π stacking were coated with macrophage membrane (MM) for effective target and accumulation in atherosclerotic lesions. Therapy of KPF@MM-NPs afforded significant decrease in proliferating macrophage inflammation while went with the reduction of key pro-inflammatory cytokines and re-polarization M1 to M2 phenotype, inducing excellent anti-AS responses in ApoE−/− mice after i.p. delivery. The mechanism of KPF@MM-NPs was further investigated and found it related to block the ROS/NF-κB signaling pathways. Together with as well demonstrated biosafety profiles, this proof-of-concept opens an instructive door for the study of KPF-mediated nanodrugs in treatment of AS based on biomimetic NPs. A macrophage-biomimetic KPF delivery platform, KPF@MM-NPs where ROS-responsive Dextran-g-PBMEO NPs were coated with MM to home towards the sites of plaque inflammation for chronic AS therapy was fabricated for the first time. KPF@MM-NPs suppressed the inflammatory macrophages proliferation via inhibition ROS/NF-κB pathways and re-polarization M1 to M2 phenotype, thereby inducing excellent anti-AS responses in ApoE−/− mice after i.p. delivery. [Display omitted] •Kaempferol (KPF) was developed as a novel anti-inflammatory drug for AS treatment.•A macrophage-clocked Dextran-g-PBMEO NPs was fabricated for KPF delivery in vivo.•The proposed NPs exhibited excellent anti-AS effect in ApoE−/− mice model.•M1 to M2 polarization via NF-κB pathway was associated with anti-AS of KPF NPs.