Nanoemulsions Target to Ectopic Lymphoids in Inflamed Joints to Restore Immune Tolerance in Rheumatoid Arthritis

被引:43
作者
Li, Chenglong [1 ]
Chen, Xiaoyan [1 ]
Luo, Xianjin [1 ]
Wang, Hairui [1 ]
Zhu, Yining [1 ]
Du, Guangshen [1 ]
Chen, Wenfei [1 ]
Chen, Zhengjun [1 ]
Hao, Xinyan [1 ]
Zhang, Zhirong [1 ]
Sun, Xun [1 ]
机构
[1] Sichuan Univ, West China Sch Pharm, Key Lab Drug Targeting & Drug Delivery Syst, Minist Educ, Chengdu 610041, Peoples R China
基金
中国国家自然科学基金;
关键词
Rheumatoid arthritis; Immune tolerance; Ectopic lymphoid structures; Nanoemulsions; Citrullinated multiepitope self-antigen; Rapamycin; REGULATORY T-CELLS; II COLLAGEN; CITRULLINATED PROTEINS; DENDRITIC CELLS; INDUCTION; NANOPARTICLES; NEOGENESIS; AUTOIMMUNITY; STRATEGIES; MODELS;
D O I
10.1021/acs.nanolett.0c05110
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Inducing immune tolerance through repeated administration of self-antigens is a promising strategy for treating rheumatoid arthritis (RA), and current research indicates that coadministration of immunomodulators can further orchestrate the tolerogenic response. However, most of the clinical trials based on tolerance induction have negligible therapeutic effects. Peripheral lymphoid organs play critical roles in immunotherapy. Here, we design an engineered nanoemulsion for targeted codelivery of self-antigens and an immunomodulator to ectopic lymphoid structures (ELSs) in inflamed joints of RA. Namely, a citrullinated multiepitope self-antigen (Cite) and rapamycin are incorporated into the nanoemulsions (NEs@CitP/Rapa), which are fabricated by a facial method using commercialized pharmaceutical excipients. After intravenous administration, the nanoemulsion shows satisfactory accumulation in the inflamed paws and provides enhanced anti-inflammatory effect in various experimental murine models of RA. Our study provides a promising targeting strategy to induce immune tolerance for the treatment of RA.
引用
收藏
页码:2551 / 2561
页数:11
相关论文
共 50 条
[1]   Induction of immune tolerance in the treatment of rheumatoid arthritis [J].
Albani, Salvatore ;
Koffeman, Eva C. ;
Prakken, Berent .
NATURE REVIEWS RHEUMATOLOGY, 2011, 7 (05) :273-282
[2]   Diagnosis and Management of Rheumatoid Arthritis A Review [J].
Aletaha, Daniel ;
Smolen, Josef S. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2018, 320 (13) :1360-1372
[3]   Lymphoid neogenesis in chronic inflammatory diseases [J].
Aloisi, F ;
Pujol-Borrell, R .
NATURE REVIEWS IMMUNOLOGY, 2006, 6 (03) :205-217
[4]   TOR in the immune system [J].
Araki, Koichi ;
Ellebedy, Ali H. ;
Ahmed, Rafi .
CURRENT OPINION IN CELL BIOLOGY, 2011, 23 (06) :707-715
[5]   The Importance of Dendritic Cells in Maintaining Immune Tolerance [J].
Audiger, Cindy ;
Rahman, M. Jubayer ;
Yun, Tae Jin ;
Tarbell, Kristin V. ;
Lesage, Sylvie .
JOURNAL OF IMMUNOLOGY, 2017, 198 (06) :2223-2231
[6]   A pilot trial of oral type II collagen in the treatment of juvenile rheumatoid arthritis [J].
Barnett, ML ;
Combitchi, D ;
Trentham, DE .
ARTHRITIS AND RHEUMATISM, 1996, 39 (04) :623-628
[7]   Stromal Fibroblasts in Tertiary Lymphoid Structures: A Novel Target in Chronic inflammation [J].
Barone, Francesca ;
Gardner, David H. ;
Nayar, Saba ;
Steinthal, Nathalie ;
Buckley, Christopher D. ;
Luther, Sanjiv A. .
FRONTIERS IN IMMUNOLOGY, 2016, 7
[8]   Citrullinated peptide dendritic cell immunotherapy in HLA risk genotype-positive rheumatoid arthritis patients [J].
Benham, Helen ;
Nel, Hendrik J. ;
Law, Soi Cheng ;
Mehdi, Ahmed M. ;
Street, Shayna ;
Ramnoruth, Nishta ;
Pahau, Helen ;
Lee, Bernett T. ;
Ng, Jennifer ;
Brunck, Marion E. G. ;
Hyde, Claire ;
Trouw, Leendert A. ;
Dudek, Nadine L. ;
Purcell, Anthony W. ;
O'Sullivan, Brendan J. ;
Connolly, John E. ;
Paul, Sanjoy K. ;
Le Cao, Kim-Anh ;
Thomas, Ranjeny .
SCIENCE TRANSLATIONAL MEDICINE, 2015, 7 (290)
[9]   Ectopic lymphoid neogenesis in rheumatic autoimmune diseases [J].
Bombardieri, Michele ;
Lewis, Myles ;
Pitzalis, Costantino .
NATURE REVIEWS RHEUMATOLOGY, 2017, 13 (03) :141-154
[10]   Emerging cell and cytokine targets in rheumatoid arthritis [J].
Burmester, Gerd R. ;
Feist, Eugen ;
Doerner, Thomas .
NATURE REVIEWS RHEUMATOLOGY, 2014, 10 (02) :77-88