Engineered PD-1/TIGIT dual-activating cell-membrane nanoparticles with dexamethasone act synergistically to shape the effector T cell/Treg balance and alleviate systemic lupus erythematosus.
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| Abstract |
Systemic lupus erythematosus (SLE) is a potentially life-threatening autoimmune disease that is characterized by alterations in the balance between effector and regulatory CD4+ T cells. We observed the upregulation of the immune checkpoints (ICs) PD-1 and TIGIT in pathogenic CD4+ T cells during disease progression, and downregulation of their ligands PD-L1 and CD155. Inspired by biomimetic nanotechnology, we fabricated dexamethasone (DXM)-loaded IFN-γ-treated MHC class I deficient cancer membrane-coated nanoparticles (IM-MNPs/DXM) to safely harness the immunosuppressive power of tumor cells for the treatment of SLE. The IM-MNPs inherited the membrane functions, which allowed these particles to evade immune clearance and accumulate in inflammatory organs. The IM-MNPs specifically targeted SLE CD4+ T cells and agonist PD-1/TIGIT signaling to inhibit effector T cell function while enhancing the immunosuppressive function of regulatory T cells (Tregs). The sustained release of DXM inhibited the production of proinflammatory cytokines in the inflammatory microenvironment to further promote Treg-mediated immune homeostasis. The IM-MNPs/DXM showed significant therapeutic efficacy in ameliorating lupus nephritis (LN) and decreasing side effects in vivo. Therefore, the particle represents a promising platform to improve current SLE treatment efficacy while minimizing systemic side effects of DXM and ICs agonist therapy.
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| Authors | Qianqian Guo, Chuanrong Chen, Zhihua Wu, Wei Zhang, Liting Wang, Jian Yu, Longxia Li, Jiali Zhang, Yourong Duan |
| Journal | Biomaterials (Biomaterials) Vol. 285 Pg. 121517 (06 2022) ISSN: 1878-5905 [Electronic] Netherlands |
| PMID | 35504179 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2022 Elsevier Ltd. All rights reserved. |
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