Abstract
BackgroundIt is unclear whether plant-derived extracellular vesicles (EVs) can mediate interspecies communication with mammalian cells. Tumor-associated macrophages (TAMs) display a continuum of different polarization states between tumoricidal M1 phenotype and tumor-supportive M2 phenotypes, with a lower M1/M2 ratio correlating with tumor growth, angiogenesis and invasion. We investigated whether EVs from ginseng can alter M2-like polarization both in vitro and in vivo to promote cancer immunotherapy.MethodsA novel EVs-liked ginseng-derived nanoparticles (GDNPs) were isolated and characterized from Panax ginseng C. A. Mey. Using GDNPs as an immunopotentiator for altering M2 polarized macrophages, we analyzed associated surface markers, genes and cytokines of macrophages treated with GDNPs. Mice bearing B16F10 melanoma were treated with GDNPs therapy. Tumor growth were assessed, and TAM populations were evaluated by FACS and IF.ResultsGDNPs significantly promoted the polarization of M2 to M1 phenotype and produce total reactive oxygen species, resulting in increasing apoptosis of mouse melanoma cells. GDNP-induced M1 polarization was found to depend upon Toll-like receptor (TLR)-4 and myeloid differentiation antigen 88 (MyD88)-mediated signaling. Moreover, ceramide lipids and proteins of GDNPs may play an important role in macrophage polarization via TLR4 activation. We found that GDNPs treatment significantly suppressed melanoma growth in tumor-bearing mice with increased presence of M1 macrophages detected in the tumor tissue.ConclusionsGDNPs can alter M2 polarization both in vitro and in vivo, which contributes to an antitumor response. The polarization of macrophages induced by GDNPs is largely dependent on TLR4 and MyD88 signalling. GDNPs as an immunomodulator participate in mammalian immune response and may represent a new class of nano-drugs in cancer immunotherapy.
Highlights
It is unclear whether plant-derived extracellular vesicles (EVs) can mediate interspecies communication with mammalian cells
We show that Ginseng-derived nanoparticle (GDNP) induce M1-like macrophage polarization via Toll-like receptor (TLR)-4/myeloid differentiation antigen 88 (MyD88) signalling pathway and enhance production of total reactive oxygen species (ROS) to induce apoptosis of mouse melanoma cells
Extracts from ginseng roots are enriched for nanoparticles, suggesting that ginseng could produce a large amount of GDNPs
Summary
It is unclear whether plant-derived extracellular vesicles (EVs) can mediate interspecies communication with mammalian cells. We investigated whether EVs from ginseng can alter M2-like polarization both in vitro and in vivo to promote cancer immunotherapy. Recent studies have indicated that these plant-derived nanoparticle-like EVs may be involved in plant cell–cell communication as a means to regulate plant innate immunity [11]. Some plant-derived EVs may mediate cross-species RNA interference causing fungal gene silencing [12]. It has never been reported previously whether ginseng release nanoparticle-like EVs, let alone the physiological function of plant-derived EVs in mammalian cells
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
