Ginseng-derived nanoparticles alter macrophage polarization to inhibit melanoma growth
Meng Cao1, Huaijiang Yan1, Xuan Han1
1Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Background:
It 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.
Methods:
A 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.
Results:
GDNPs 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.
Conclusions:
GDNPs 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.
Insights
Ginseng-derived nanoparticles (GDNPs) reprogram tumor-associated macrophages (TAMs) from M2 to M1, enhancing anti-cancer immunity. This plant-derived nanoparticle therapy suppressed melanoma growth and shows potential as a novel cancer immunotherapy.
Area of Science:
- Plant-derived extracellular vesicles (EVs) and their role in interspecies communication.
- Immunology and cancer immunotherapy.
- Nanomedicine and drug delivery systems.
Background:
- Tumor-associated macrophages (TAMs) exist on a spectrum from M1 (tumoricidal) to M2 (tumor-supportive) phenotypes.
- A lower M1/M2 ratio in TAMs correlates with increased tumor growth, angiogenesis, and invasion.
- The potential of plant-derived EVs to modulate mammalian cell communication and immune responses remains largely unexplored.
Purpose of the Study:
- To investigate if extracellular vesicles (EVs) derived from ginseng can modulate M2-like macrophage polarization.
- To assess the potential of ginseng-derived nanoparticles (GDNPs) to promote cancer immunotherapy.
- To evaluate the in vitro and in vivo effects of GDNPs on melanoma progression and TAM polarization.
Main Methods:
- Isolation and characterization of novel EVs-like ginseng-derived nanoparticles (GDNPs) from Panax ginseng.
- Analysis of macrophage surface markers, genes, and cytokines following GDNP treatment.
- In vivo studies using B16F10 melanoma-bearing mice treated with GDNPs, assessing tumor growth and TAM populations via flow cytometry and immunofluorescence.
Main Results:
- GDNPs significantly promoted M2 to M1 macrophage polarization, increasing reactive oxygen species production and melanoma cell apoptosis.
- GDNP-induced M1 polarization was mediated by Toll-like receptor (TLR)-4 and myeloid differentiation antigen 88 (MyD88) signaling pathways.
- GDNPs treatment suppressed melanoma growth in vivo, accompanied by an increased presence of M1 macrophages in tumor tissues.
Conclusions:
- Ginseng-derived nanoparticles (GDNPs) effectively alter M2 macrophage polarization to M1 both in vitro and in vivo, contributing to an antitumor response.
- Macrophage polarization induced by GDNPs is dependent on TLR4 and MyD88 signaling.
- GDNPs function as immunomodulators in mammalian immune responses, representing a potential new class of nano-drugs for cancer immunotherapy.
