Carbon nanospheres mediated delivery of nuclear matrix protein SMAR1 to direct experimental autoimmune encephalomyelitis in mice.
Owing to the suppression of immune responses and associated side effects, steroid based treatments for inflammatory encephalitis disease can be detrimental. Here, we demonstrate a novel carbon nanosphere (CNP) based treatment regime for encephalomyelitis in mice by exploiting the functional property of the nuclear matrix binding protein SMAR1. A truncated part of SMAR1 ie, the DNA binding domain was conjugated with hydrothermally synthesized CNPs. When administered intravenously, the conjugate suppressed experimental animal encephalomyelitis in T cell specific conditional SMAR1 knockout mice (SMAR(-/-)). Further, CNP-SMAR1 conjugate delayed the onset of the disease and reduced the demyelination significantly. There was a significant decrease in the production of IL-17 after re-stimulation with MOG. Altogether, our findings suggest a potential carbon nanomaterial based therapeutic intervention to combat Th17 mediated autoimmune diseases including experimental autoimmune encephalomyelitis.
Disease and Chromatin Biology Laboratory, National Center for Cell Science, Pune University Campus, Pune, Maharashtra, India.
Sijo V
SV
Chemmannur
Center for Nanobioscience, Agharkar Research Institute, Pune, Maharashtra, India.
Prasad
P
Bhagat
Disease and Chromatin Biology Laboratory, National Center for Cell Science, Pune University Campus, Pune, Maharashtra, India.
Bhalchandra
B
Mirlekar
Center for Nanobioscience, Agharkar Research Institute, Pune, Maharashtra, India.
Kishore M
KM
Paknikar
Disease and Chromatin Biology Laboratory, National Center for Cell Science, Pune University Campus, Pune, Maharashtra, India; Indian Institute of Chemical Biology, Kolkata, India.
Samit
S
Chattopadhyay
D000818:Animals; D002244:Carbon / Q000737:chemistry*; D018797:Cell Cycle Proteins / Q000008:administration & dosage* / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000008:administration & dosage* / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology; D004705:Endocytosis / Q000187:drug effects; D015850:Interleukin-6 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054118:Nanospheres / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000008:administration & dosage* / Q000627:therapeutic use*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects
C485952:Banp protein, mouse; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; D050796:STAT3 Transcription Factor; D002244:Carbon
EAE; IL-17; SMAR1; Th17; carbon nanospheres