Carbon nanospheres mediated delivery of nuclear matrix protein SMAR1 to direct experimental autoimmune encephalomyelitis in mice

Abstract

Sijo V Chemmannur,1,* Prasad Bhagat,2,* Bhalchandra Mirlekar,1 Kishore M Paknikar,2 Samit Chattopadhyay1,3 1Disease and Chromatin Biology Laboratory, National Center for Cell Science, Pune University Campus, Pune, Maharashtra, India; 2Center for Nanobioscience, Agharkar Research Institute, Pune, Maharashtra, India; 3Indian Institute of Chemical Biology, Kolkata, India *These authors have contributed equally to this work Abstract: 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. Keywords: carbon nanospheres, EAE, IL-17, SMAR1, Th17

Keywords

• Carbon nanospheres
• EAE
• IL-17
• SMAR1
• Th17