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核心技术专利：CN118964589B侵权必究
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可生物降解的电纺聚乳酸-羟基乙酸共聚物纳米纤维包裹旋毛虫抗原可预防复发性实验性自身免疫性脑脊髓炎及相关肠道微生物群失调。

Biodegradable Electrospun PLGA Nanofibers-Encapsulated Trichinella Spiralis Antigens Protect from Relapsing Experimental Autoimmune Encephalomyelitis and Related Gut Microbiota Dysbiosis.

作者信息

Sabljić Ljiljana, Radulović Nataša, Đokić Jelena, Stojanovic Dusica B, Radojević Dušan, Glamočlija Sofija, Dinić Miroslav, Golić Nataša, Vasilev Saša, Uskoković Petar, Sofronić-Milosavljević Ljiljana, Gruden-Movsesijan Alisa, Tomić Sergej

机构信息

Institute for the Application of Nuclear Energy, University of Belgrade, Belgrade, Serbia.

Institute for Biological Research "Siniša Stanković", University of Belgrade, Belgrade, Serbia.

出版信息

Int J Nanomedicine. 2025 Feb 12;20:1921-1948. doi: 10.2147/IJN.S499161. eCollection 2025.

DOI:10.2147/IJN.S499161
PMID:39963417
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11830953/
Abstract

PURPOSE: has evolved complex immunomodulatory mechanisms mediated by excretory-secretory products (ESL1) that enable its survival in the host. Consequently, ESL1 antigens display excellent potential for treating autoimmune diseases such as multiple sclerosis (MS). However, whether timely controlled delivery of ESL1 antigens in vivo, as in natural infections, could enhance its therapeutic potential for MS is still unknown. METHODS: To test this, we encapsulated ESL1 antigens into biodegradable poly (lactide-co-glycolic) acid (PLGA) nanofibers by emulsion electrospinning as a delivery system and assessed their release dynamics in vitro, and in an animal MS model, experimental autoimmune encephalomyelitis (EAE), induced 7 days after PLGA/ESL1 subcutaneous implantation. PLGA/ESL1 effects on EAE symptoms were monitored along with multiple immune cell subsets in target organs at the peak and recovery of EAE. Gut barrier function and microbiota composition were analyzed using qPCR, 16S rRNA sequencing, and metabolomic analyses. RESULTS: ESL1 antigens, released from PLGA and drained via myeloid antigen-presenting cells through lymph nodes, protected the animals from developing EAE symptoms. These effects correlated with reduced activation of myeloid cells, increased IL-10 expression, and reduced accumulation of proinflammatory natural killer (NK) cells, T helper (Th)1 and Th17 cells in the spleen and central nervous system (CNS). Additionally, CD4CD25FoxP3 regulatory T cells and IL-10-producing B cells were expanded in PLGA/ESL1-treated animals, compared to control animals. The migration of ESL1 to the guts correlated with locally reduced inflammation and gut barrier damage. Additionally, PLGA/ESL1-treated animals displayed an unaltered microbiota characterized only by a more pronounced protective mevalonate pathway and expanded short-chain fatty acid-producing bacteria, which are known to suppress inflammation. CONCLUSION: The delivery of ESL1 antigens via biodegradable electrospun PLGA nanofiber implants efficiently protected the animals from developing EAE by inducing a beneficial immune response in the spleen, gut, and CNS. This platform provides excellent grounds for further development of novel MS therapies.

摘要

目的：已进化出由排泄分泌产物（ESL1）介导的复杂免疫调节机制，使其能够在宿主体内存活。因此，ESL1抗原在治疗自身免疫性疾病如多发性硬化症（MS）方面显示出巨大潜力。然而，像在自然感染中那样在体内及时控制ESL1抗原的递送是否能增强其对MS的治疗潜力仍不清楚。 方法：为了验证这一点，我们通过乳液静电纺丝将ESL1抗原封装到可生物降解的聚（丙交酯-共-乙交酯）酸（PLGA）纳米纤维中作为递送系统，并评估其在体外以及在PLGA/ESL1皮下植入7天后诱导的实验性自身免疫性脑脊髓炎（EAE）动物MS模型中的释放动力学。在EAE的高峰期和恢复期，监测PLGA/ESL1对EAE症状的影响以及靶器官中多种免疫细胞亚群的情况。使用qPCR、16S rRNA测序和代谢组学分析来分析肠道屏障功能和微生物群组成。 结果：从PLGA释放并通过髓样抗原呈递细胞经淋巴结排出的ESL1抗原保护动物不出现EAE症状。这些作用与髓样细胞活化减少、IL-10表达增加以及脾脏和中枢神经系统（CNS）中促炎性自然杀伤（NK）细胞、辅助性T（Th）1和Th17细胞的积累减少相关。此外，与对照动物相比，在经PLGA/ESL1处理的动物中，CD4CD25FoxP3调节性T细胞和产生IL-10的B细胞有所增加。ESL1向肠道的迁移与局部炎症减轻和肠道屏障损伤减少相关。此外，经PLGA/ESL1处理的动物显示微生物群未改变，其特征仅为更明显的保护性甲羟戊酸途径和产生短链脂肪酸的细菌增加，已知这些细菌可抑制炎症。 结论：通过可生物降解的静电纺丝PLGA纳米纤维植入物递送ESL1抗原可通过在脾脏、肠道和CNS中诱导有益的免疫反应，有效保护动物不出现EAE。该平台为进一步开发新型MS疗法提供了良好基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/11830953/bf0e2d883803/IJN-20-1921-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/11830953/c32a8a784c1a/IJN-20-1921-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/11830953/6a0303682e62/IJN-20-1921-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/11830953/f3b9a7351133/IJN-20-1921-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/11830953/5d7732b6a3c0/IJN-20-1921-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/11830953/1da78847bef9/IJN-20-1921-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/11830953/95f2afce04fd/IJN-20-1921-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/11830953/d571b5af21db/IJN-20-1921-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/11830953/7bfe0b008128/IJN-20-1921-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/11830953/bf0e2d883803/IJN-20-1921-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/11830953/c32a8a784c1a/IJN-20-1921-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/11830953/6a0303682e62/IJN-20-1921-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/11830953/f3b9a7351133/IJN-20-1921-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/11830953/5d7732b6a3c0/IJN-20-1921-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/11830953/1da78847bef9/IJN-20-1921-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/11830953/95f2afce04fd/IJN-20-1921-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/11830953/d571b5af21db/IJN-20-1921-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/11830953/7bfe0b008128/IJN-20-1921-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/11830953/bf0e2d883803/IJN-20-1921-g0009.jpg

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[2]
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[3]
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本文引用的文献

[1]
Extracellular vesicles from adipose mesenchymal stem cells target inflamed lymph nodes in experimental autoimmune encephalomyelitis.

Cytotherapy. 2024-3

[2]
Myeloid-derived suppressor cells in the therapy of autoimmune diseases.

Eur J Immunol. 2023-12

[3]
Challenges in tolerogenic dendritic cell therapy for autoimmune diseases: the route of administration.

Immunother Adv. 2023-7-18

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Diet prevents the expansion of segmented filamentous bacteria and ileo-colonic inflammation in a model of Crohn's disease.

Microbiome. 2023-3-31

[5]
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Nat Rev Immunol. 2023-11

[6]
Effect of Electrospun PLGA/Collagen Scaffolds on Cell Adhesion, Viability, and Collagen Release: Potential Applications in Tissue Engineering.

Polymers (Basel). 2023-2-21

[7]
In Vitro and In Vivo Cell-Interactions with Electrospun Poly (Lactic-Co-Glycolic Acid) (PLGA): Morphological and Immune Response Analysis.

Polymers (Basel). 2022-10-21

[8]
Myeloid-derived suppressor cells prevent disruption of the gut barrier, preserve microbiota composition, and potentiate immunoregulatory pathways in a rat model of experimental autoimmune encephalomyelitis.

Gut Microbes. 2022

[9]
Immunomodulatory components of excretory-secretory products with lactose-binding specificity.

EXCLI J. 2022-6-3

[10]
The role of the gut microbiota in multiple sclerosis.

Nat Rev Neurol. 2022-9

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