Carbon nanotubes (CNT)-loaded ginsenosides Rb3 suppresses the PD-1/PD-L1 pathway in triple-negative breast cancer

Abstract

Carbon nanotubes (CNTs), as advanced nanotechnology with specific properties and structures, have presented practical drug delivery properties. Ginsenoside Rg3 is a component of puffed ginseng and demonstrates anti-cancer activities. To explore the effect of CNTs-loaded Rg3 (Rg3-CNT) on the PD-1/PD-L1 signaling and the development of triple-negative breast cancer (TNBC). Our data revealed that Rg3 inhibited the cell viability of TNBC cells, in which Rg3-CNT further enhanced this effect in the system. Similarly, the colony formation of TNBC cells was decreased by Rg3, while Rg3-CNT could reinforce its effect in the cells. Besides, the treatment of Rg3 induced apoptosis of TNBC cells, in which Rg3-CNT treatment further increased the phenotype in the cells. Remarkably, Rg3-CNT, but not Rg3, attenuated PD-L1 expression in TNBC cells. Rg3-CNT decreased the PD-L1 upregulation induced by interferon-γ (IFN-γ) in breast cancer cells. Importantly, Rg3-CNT was able to reduce PD-1 expression in activated T cells. Specifically, Rg3-CNT reduced the PD-1/PD-L1 axis in a T cell/triple-negative TNBC cell co-culture system. Moreover, the levels of IFN-γ, interleukins-2 (IL-2), interleukins-9 (IL-9), interleukins-10 (IL-10), interleukins-22 (IL-22), and interleukins-23 (IL-23) were significantly stimulated in the activated T cells, while the treatment of Rg3-CNT could reverse these phenotypes in the cells. Rg3-CNT attenuated the TNBC cell growth in vivo. The Rg3-CNT improved the anti-cancer effect of Rg3 toward TNBC by inhibiting the PD-1/PD-L1 axis. Our finding provides new insights into the mechanism by which Rg3-CNT attenuates the development of TNBC. Rg3-CNT may be applied as the potential therapeutic strategy for immunotherapy of TNBC.

Immunomodulatory potential of natural products from herbal medicines as immune checkpoints inhibitors: Helping to fight against cancer via multiple targets

“…Moreover, ginsenoside Rh2 can enhance CD4 + and CD8a + T‐cell infiltration in the tumor tissues of melanoma (B16‐F10)‐bearing mice, and ginsenoside Rg1 can increase CD4 + T‐cell proliferation and activity in mice 131,174 . Importantly, carbon nanotubes‐loaded ginsenoside Rg3 can reduce PD‐1 expression in activated T cells and attenuate PD‐L1 expression in triple‐negative breast cancer cells, thereby stimulating the production of IFN‐γ, IL‐2, IL‐9, IL‐10, IL‐22, and IL‐23 from the activated T cells and attenuating the MDA‐MB‐231 breast cancer cell growth in vivo 130 . However, it is not clear whether ginsenosides target CTLA‐4.…”

“…131 , 174 Importantly, carbon nanotubes‐loaded ginsenoside Rg3 can reduce PD‐1 expression in activated T cells and attenuate PD‐L1 expression in triple‐negative breast cancer cells, thereby stimulating the production of IFN‐γ, IL‐2, IL‐9, IL‐10, IL‐22, and IL‐23 from the activated T cells and attenuating the MDA‐MB‐231 breast cancer cell growth in vivo. 130 However, it is not clear whether ginsenosides target CTLA‐4.…”

Emergence of Nanotechnology as a Powerful Cavalry against Triple-Negative Breast Cancer (TNBC)

“…Further, it was observed that Rg3 impaired the upregulation of PD-L1 in activated T-cells. Moreover, treatment with CNTs reduced the levels of interleukins (IL-2, Il-9, Il-10, IL-22, and IL-23) and interferons (IFN-ϒ), thereby attenuating the PD-L1 signaling pathway [ 278 ].…”

Insights on functionalized carbon nanotubes for cancer theranostics

“…Recently, Luo et al . designed a nanosystem composed of MWNTs-loaded ginsenoside Rg3 (Rg3-CNT) for triple-negative breast cancer (TNBC) treatment, which firstly demonstrated the new function of Rg3-CNT in elevating the therapeutic efficacy of Rg3 against TNBC through the inhibition of PD-1/PD-L1 axis, providing a potential strategy for TNBC treatment through immunotherapy [ 78 ]. In their study, Rg3-CNT was found to reduce PD-L1 expression and PD-L1 upregulation induced by IFN-γ in TNBC cells, meanwhile, PD-1 expression, PD-1/PD-L1 signaling were also suppressed, which remarkably inhibited the TNBC cell growth in vivo.…”