Research Projects

Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by chronic inflammatory illness with heterogeneous clinical manifestations leading to damage to organs or systems. This autoimmune disease is defined by immune system dysregulation, with B cells playing a central and multifaceted role in its pathogenesis. The central and peripheral tolerance mechanisms that normally deactivate self-reactive B cells are compromised in lupus conditions. This makes it possible for autoreactive B cells to survive, develop, and take part in the autoimmune process. Altered B cell receptor signalling lowers the activation threshold for B cells, increase calcium influx and downstream signals. This enables autoreactive B cells to survive, activate, and produce autoantibodies. Current therapies are non-specific, suppress the entire immune system, and cause side effects. More targeted,effective treatments are needed to modulate B cell function without broad immunosuppression. To address this, a novel therapeutic platform is proposed using MXene-gold nanoparticles (MXene-AuNPs) with aptamers targeting B cell specific markers CD19/CD20. MXenes are biocompatible, tunable 2D materials well-suited for drug delivery. Gold nanoparticles (AuNPs) add stability and allow easy conjugation of aptamers—short nucleic acids that bind specifically to B cell markers. This ensures selective, precise drug delivery to B cells while minimising harm to healthy tissues. The current proposal outlines the development of two innovative MXene-AuNPs-aptamer-based drug delivery systems to target B cells in systemic lupus erythematosus. The system 1 utilises CD19/CD20 specific aptamer-functionalized MXene-AuNPs to deliver the P140 peptide, which modulates B cell function and system 2 employs the same versatile nanoplatform to selectively deliver BCL6 siRNA molecule, a gene-silencing agent that reduces autoantibody production by inhibiting germinal centre B cell survival. Both strategies exploit the nanocarrier’s stability, targeting ability, and versatility to deliver therapeutics with enhanced safety and efficacy for lupus treatment. These dual approaches represent a significant advancement in the pursuit of precision nanomedicine for systemic lupus erythematosus, offering new avenues for safer, more effective, and personalised treatment strategies. Scientific objectives of the proposed study includes . 1. Design and synthesise CD19/CD20 specific aptamer functionalised MXene-AuNPs-nanocarriers. 2. Evaluate the biocompatibility, specificity of CD19/CD20 aptamer-mediated targeting and cellular uptake of the nanocarriers in immune cell populations. 3. Investigate the immunomodulatory effects of system1(P140 peptide-loaded nano carriers) on B cell function and activation in vitro. 4. Assess the gene-silencing efficacy of system 2 (BCL6 siRNA-loaded nanocarriers) in suppressing BCL6 expression in B cells.