Иммунологическая терпимость, вызванная нанолипосомой с автоантигенией Пептид и артесунатом в дополнение к инхибиту и перемоделировать иммунный баланс для лечения множественного склероза.

Immunological Tolerance Induced by Nanoliposome with Autoantigenie Peptide and Artesunate to Inhibit Complement and Remodel Immune Balance for Multiple Sclerosis Treatment.

Multiple sclerosis (MS) is a demyelinating autoimmune disease (AD) accompanied by immune disorders and complement over activation. Although re-instatement of immune balance does alleviate MS symptoms, exploration of concomitant complement inhibition for neuron protection has not been evaluated. Herein, we developed myelin oligodendrocyte glycoprotein 35-55 (MOG) peptide and artemisinin (ART) co-loaded liposomes (MOG-ART-Lip) to simultaneously restore immune balance and inhibit complement activation. This nanoplatform enhanced solubility of both components while enabling CNS delivery. Liposomes loaded with MOG would induce tolerogenic DCs (tol-DCs) that express low-levels of costimulatory molecules, capable of antigenic peptide presentation and induction of regulatory T cells, while ART shifted microglia from pro-inflammatory (M1) to anti-inflammatory (M2) phenotypes. Importantly, ART suppressed complement-mediated demyelination via the C3/C3a receptor (C3aR) pathway. In vivo studies showed MOG-ART-Lip significantly reduced neuroinflammation, attenuated demyelination, and promoted neural repair, leading to functional recovery. Overall, results of this study suggest that a combination of an auto-antigenic peptide and an immune-modulator provides a promising modality for the treatment of MS by re-establishing antigen-specific immune tolerance. As such, the results of the study provide valuable insight into a new approach for development of combinatorial complement therapies for the treatment of MS patients.