Ginseng-derived nanoparticles alter macrophage polarization to inhibit melanoma growth
Abstract 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 phenotyp...
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doaj-ece6e8e0dbbd4dd496b6bcdd559a8d352020-11-25T03:08:28ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262019-11-017111810.1186/s40425-019-0817-4Ginseng-derived nanoparticles alter macrophage polarization to inhibit melanoma growthMeng Cao0Huaijiang Yan1Xuan Han2Ling Weng3Qin Wei4Xiaoyan Sun5Wuguang Lu6Qingyun Wei7Juan Ye8Xueting Cai9Chunping Hu10Xiaoyang Yin11Peng Cao12Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAbstract 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.http://link.springer.com/article/10.1186/s40425-019-0817-4Extracellular vesicles (EVs)Ginseng-derived nanoparticlesTumor-associated macrophages (TAM)Macrophage polarizationMelanoma |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Meng Cao Huaijiang Yan Xuan Han Ling Weng Qin Wei Xiaoyan Sun Wuguang Lu Qingyun Wei Juan Ye Xueting Cai Chunping Hu Xiaoyang Yin Peng Cao |
spellingShingle |
Meng Cao Huaijiang Yan Xuan Han Ling Weng Qin Wei Xiaoyan Sun Wuguang Lu Qingyun Wei Juan Ye Xueting Cai Chunping Hu Xiaoyang Yin Peng Cao Ginseng-derived nanoparticles alter macrophage polarization to inhibit melanoma growth Journal for ImmunoTherapy of Cancer Extracellular vesicles (EVs) Ginseng-derived nanoparticles Tumor-associated macrophages (TAM) Macrophage polarization Melanoma |
author_facet |
Meng Cao Huaijiang Yan Xuan Han Ling Weng Qin Wei Xiaoyan Sun Wuguang Lu Qingyun Wei Juan Ye Xueting Cai Chunping Hu Xiaoyang Yin Peng Cao |
author_sort |
Meng Cao |
title |
Ginseng-derived nanoparticles alter macrophage polarization to inhibit melanoma growth |
title_short |
Ginseng-derived nanoparticles alter macrophage polarization to inhibit melanoma growth |
title_full |
Ginseng-derived nanoparticles alter macrophage polarization to inhibit melanoma growth |
title_fullStr |
Ginseng-derived nanoparticles alter macrophage polarization to inhibit melanoma growth |
title_full_unstemmed |
Ginseng-derived nanoparticles alter macrophage polarization to inhibit melanoma growth |
title_sort |
ginseng-derived nanoparticles alter macrophage polarization to inhibit melanoma growth |
publisher |
BMJ Publishing Group |
series |
Journal for ImmunoTherapy of Cancer |
issn |
2051-1426 |
publishDate |
2019-11-01 |
description |
Abstract 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. |
topic |
Extracellular vesicles (EVs) Ginseng-derived nanoparticles Tumor-associated macrophages (TAM) Macrophage polarization Melanoma |
url |
http://link.springer.com/article/10.1186/s40425-019-0817-4 |
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