The Mechanism Of Ginseng-derived Nanoparticles(GDNPs) Reprogram Macrophages Through Toll-like Receptor 4

Objective:With the rapid development of modern immunology and the advancement of basic research in traditional Chinese medicine,the regulatory effect of traditional Chinese medicine on the immune system has attracted more and more attention from researchers.More and more results show that some Chinese medicines can regulate the activity of the innate immune system,while other Chinese medicines target adaptive immune cell subgroups.The mechanism is still unclear.Therefore,the research on the immune mechanism of traditional Chinese medicine is a key issue in the research of traditional Chinese medicine.In recent years,vesicle-like nanoparticles have been extracted from a variety of edible plants.Whether plant-derived extracellular vesicles can mediate inter-species communication with mammalian cells is unclear,and its impact on the body is unclear.Methods:We extracted vesicle-like nanoparticles(Ginseng-derived nanoparticles,GDNPs)from fresh ginseng,and carried out structural characterization and composition analysis.Using GDNPs as immune enhancers to change M2 polarized macrophages,we analyzed in vitro the relevant surface markers,genes and cytokines of macrophages treated with GDNPs.B16F10 melanoma mice were treated with GDNPs in vivo to evaluate the tumor growth.Flow cytometry(FACS)and IF were used to evaluate the TAM population.IF and Western Blot were used to further study the mechanism of GDNPs.Results:The vesicle-like nanoparticles can be separated from fresh ginseng,and they have a typical cup-shaped,double-layer membrane structure.GDNPs significantly promoted the polarization of M2 to M1 phenotype,produced total reactive oxygen species,and led to increased apoptosis of mouse melanoma cells.The M1 polarization induced by GDNPs depends on signal transduction mediated by Toll-like receptor(TLR)-4 and myeloid differentiation antigen 88(MyD88).In addition,GDNPs are rich in lipid components-ceramide,which can be recognized and taken up by TLR4 on lipid rafts on the surface of macrophages,thereby activating related signal pathways.Of macrophages.We found that GDNPs treatment significantly inhibited the growth of melanoma in tumor-bearing mice,and an increase in M1 macrophages was detected in the tumor tissue.Conclusions:GDNPs can change the polarization of M2 both in vivo and in vitro,which contributes to the anti-tumor response.The polarization of macrophages induced by GDNPs mainly depends on TLR4 and MyD88 signals.As immunomodulators,GDNPs participate in the immune response of mammals,which may represent a new class of tumor immunotherapy nanomedicine,and provide a new theoretical basis and experimental basis for studying how traditional Chinese medicine regulates the body’s immune system.