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 pi-pi 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-kappa B signaling pathways. Together with as well demon-strated biosafety profiles, this proof-of-concept opens an instructive door for the study of KPF-mediated nano -drugs in treatment of AS based on biomimetic NPs.

Automated summary

Atherosclerosis is a major cause of death globally. Targeting plaque inflammation by repolarizing macrophages from pro-inflammatory to anti-inflammatory state could be a promising strategy. This study discovered the potential of kaempferol as an anti-inflammatory drug and developed a macrophage biomimetic kaempferol delivery platform for effective treatment.