Poly dispersed acid-functionalized single walled carbon nanotubes target activated T and B cells to suppress acute and chronic GVHD in mouse model

Abstract

Graft versus host disease (GVHD) results from hyper-activation of transplanted lymphocytes against the host antigens. Bone marrow transplantation in humans as well as some cases of blood transfusion and organ transplantation are associated with a strong GVH reaction resulting in GVHD that in many cases may be fatal. We had previously shown that poly-dispersed acidfunctionalized single-walled carbon nanotubes (AF-SWCNTs) specifically target activated T and B lymphocytes and kill them. In the present study, efficacy of AF-SWCNTs to suppress the GVH reaction was tested in the mouse model. Acute GVHD was induced in mice by administering intravenously 30 or 60 million spleen cells from a parental strain (C57bl/6 mouse, MHC haplotype H-2 b ) to host (C57bl/6 x Balb/c) F1 mice (MHC haplotype H-2 b/d ) and waiting for 8-10 days. Chronic GVHD was similarly induced by administration of 30 million parent spleen cells to F1 mice and waiting for a period of 60 days. Our results demonstrate a marked decline in splenomegaly and recovery of spleen T (both CD4 and CD8) and B cells in GVHD mice treated with AF-SWCNTs. AF-SWCNTs treatment also limited T and B cell proliferation by restricting S-phage of cell cycle. Generation of anti-host cytotoxic T cells (CTLs) was also markedly suppressed by AF-SWCNT treatment of acute GVHD mice, and a significant reduction in the generation of anti-host antibodies could also be demonstrated. Taken together, our results suggest that the AF-SWCNTs can be considered as a potential therapeutic agent for treating GVHD.

Toxicity of poly-dispersed single-walled carbon nanotubes on bone marrow derived Hematopoietic Stem and Progenitor Cells

“…In addition, while CNTs at present do not constitute a significant pollutant in the environment, occupational exposures to workers involved in commercial applications of CNTs is possible ( Kobayashi et al, 2017 ). Our research over last couple of decades has focused on the effects of carbon nanoparticles including CNTs on a variety of biological parameters especially the immune system ( Saxena, et al, 2007 , Stevens et al, 2006 , Sachar and Saxena, 2011 , Ma et al, 2017 , Dutt et al, 2019 , Mia and Saxena, 2020 , Alam et al, 2013 , Alam et al, 2016 , Singh et al, 2020 , Rizvi et al, 2015 , Kumari et al, 2012 ). Since the whole of the immune system basically originates in bone marrow, it is pertinent to ask the question as to how CNTs would influence the hematopoietic stem cells and ontogenesis leading to different types of immune cells.…”

“…Pristine single-walled carbon nanotubes (SWCNTs) are highly hydrophobic, form huge agglomerates insoluble in aqueous media and therefore do not interact well with biological systems like cells and tissues ( Saxena, et al, 2007 ). SWCNTs may be functionalized in a variety of ways to yield hydrophilic poly-dispersed nanotubes that interact well with cells and are therefore used in all biomedical applications ( Md and Saxena, 2018 , Sachar and Saxena, 2011 , Ma et al, 2017 , Dutt et al, 2019 , Mia and Saxena, 2020 , Alam et al, 2013 , Alam et al, 2016 , Singh et al, 2020 ). Previous reports from our group have shown that the acid-functionalized single-walled carbon nanotubes (AF-SWCNTs) may modulate bone marrow and spleen erythropoiesis ( Md and Saxena, 2018 , Sachar and Saxena, 2011 , Ma et al, 2017 ), suppress T cell and NK cell activation ( Mia and Saxena, 2020 , Alam et al, 2013 , Alam et al, 2016 ), interfere with the antigen processing and presentation, and alter epithelial tight junctions( Singh et al, 2020 , Rizvi et al, 2015 , Kumari et al, 2012 ).…”

“…SWCNTs may be functionalized in a variety of ways to yield hydrophilic poly-dispersed nanotubes that interact well with cells and are therefore used in all biomedical applications ( Md and Saxena, 2018 , Sachar and Saxena, 2011 , Ma et al, 2017 , Dutt et al, 2019 , Mia and Saxena, 2020 , Alam et al, 2013 , Alam et al, 2016 , Singh et al, 2020 ). Previous reports from our group have shown that the acid-functionalized single-walled carbon nanotubes (AF-SWCNTs) may modulate bone marrow and spleen erythropoiesis ( Md and Saxena, 2018 , Sachar and Saxena, 2011 , Ma et al, 2017 ), suppress T cell and NK cell activation ( Mia and Saxena, 2020 , Alam et al, 2013 , Alam et al, 2016 ), interfere with the antigen processing and presentation, and alter epithelial tight junctions( Singh et al, 2020 , Rizvi et al, 2015 , Kumari et al, 2012 ). Interestingly, activated T and B lymphocytes internalize significantly higher amounts of AF-SWCNTs and hence their use in down regulating immune disorders like the graft vs host disease have been suggested ( Mia and Saxena, 2020 ).…”

Immunotoxicity of Carbon-Based Nanomaterials, Starring Phagocytes

“…It is vital to suppress the activity of immune cells. Intravenous administration of SWCNTs limited the proliferation of T and B cells and was associated with lower production of anti-host cytotoxic T cells and anti-host antibodies [ 159 ]. Tosic et al proved that graphene quantum dots (GQD) inhibit neuroinflammation in rats with experimental autoimmune encephalomyelitis (EAE).…”