收稿日期: 2026-03-30
网络出版日期: 2026-06-30
基金资助
国家自然科学基金资助项目(82374494);贵州省科技厅科技计划项目(黔科合平台KXJZ[2024]034);贵州省科技厅基础研究计划面上项目(黔科合基础MS〔2026〕698);省部共建国家中医药管理局传统医学与湿病重点实验室建设项目(SZ2021ZZ0202);贵州省卫生健康委科学技术基金项目(青年B类项目)(gzwkj2026?246);贵州省教育厅青年科技人才成长项目(编号:黔教技 [2024]122号);贵州中医药大学第二附属医院“三航”人才培养工程科研人才项目(SHRC-KY2024005);贵州中医药大学第二附属医院“三航”人才培养工程科研人才项目(SHRC-KY2024022)
Research progress and translational prospects of plant-derived extracellular vesicles in the treatment of rheumatoid arthritis
Received date: 2026-03-30
Online published: 2026-06-30
类风湿关节炎(rheumatoid arthritis, RA)是一种慢性自身免疫性疾病,以慢性滑膜炎、进行性关节破坏及多系统受累为特征。现有药物治疗虽显著改善RA临床结局,但仍面临不良反应、经济负担重及部分患者应答不足等挑战。植物来源细胞外囊泡(plant-derived extracellular vesicles, PDEVs)作为一类新型天然纳米载体,兼具内源性活性与递送载体双重属性,且具有源广泛、制备便捷、免疫原性低及安全性较高等优势。近年来,PDEVs在RA治疗中的研究逐渐增多,其在免疫调节、抗炎干预及靶向递送方面的应用价值备受关注,为RA治疗提供了创新策略。该文系统总结PDEVs的结构特征、分离纯化与表征方法,重点综述其在RA治疗中的研究进展与潜在作用机制,以期为相关基础研究和临床转化提供参考。
王蕊 , 季诗煜 , 罗丰 , 王秋燚 , 姚血明 . 植物来源细胞外囊泡在类风湿关节炎治疗中的研究进展与转化前景[J]. 实用医学杂志, 2026 , 42(12) : 2179 -2184 . DOI: 10.3969/j.issn.1006-5725.2026.12.012
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovitis, progressive joint destruction, and multisystem involvement. Although current pharmacotherapies have significantly improved the clinical outcomes of RA, challenges remain, including adverse effects, high economic burden, and inadequate treatment response in some patients. Plant-derived extracellular vesicles (PDEVs), as a novel class of natural nanocarriers, possess the dual attributes of endogenous bioactivity and drug delivery vehicles, offering advantages such as broad availability, convenient preparation, low immunogenicity, and high biosafety. In recent years, research on PDEVs in the treatment of RA has been increasing, and their application value in immunomodulation, anti-inflammatory intervention, and targeted delivery has garnered considerable attention, providing innovative strategies for RA therapy. This review systematically summarizes the structural characteristics, isolation, purification, and characterization methods of PDEVs, with a focus on their research progress and underlying mechanisms in RA treatment, aiming to provide a reference for related basic research and clinical translation.
| [1] | 崔易康, 高青杰, 马俊福, 等. circ_0005276靶向miR-557调控类风湿关节炎滑膜成纤维细胞的增殖、迁移和侵袭 [J]. 实用医学杂志, 2023, 39(2): 186-191. doi.10.3969/j.issn.1006-5725.2023.02.011. |
| [2] | GAO Y F, ZHAO N, HU C H. Harnessing mesenchymal stem/stromal cells-based therapies for rheumatoid arthritis: Mechanisms, clinical applications, and microenvironmental interactions [J]. Stem Cell Res Ther, 2025, 16(1): 379. doi: 10.1186/s13287-025-04495-z . |
| [3] | YUE M, HU S, SUN H, et al. Extracellular vesicles remodel tumor environment for cancer immunotherapy [J]. Mol Cancer, 2023, 22(1): 203. doi: 10.1186/s12943-023-01898-5 . |
| [4] | KUMAR M A, BABA S K, SADIDA H Q, et al. Extracellular vesicles as tools and targets in therapy for diseases [J]. Signal Transduct Target Ther, 2024, 9(1): 27. doi: 10.1038/s41392-024-01735-1 . |
| [5] | LIU R, ZHANG F, HE X, et al. Plant Derived Exosome-Like Nanoparticles and Their Therapeutic Applications in Glucolipid Metabolism Diseases [J]. J Agric Food Chem, 2025, 73(11): 6385-6399. doi: 10.1021/acs.jafc.4c12480 . |
| [6] | CONG M, TAN S, LI S, et al. Technology insight: Plant-derived vesicles-How far from the clinical biotherapeutics and therapeutic drug carriers? [J]. Adv Drug Deliv Rev, 2022, 182: 114108. doi: 10.1016/j.addr.2021.114108 . |
| [7] | HAN R, ZHOU D, JI N, et al. Folic acid-modified ginger-derived extracellular vesicles for targeted treatment of rheumatoid arthritis by remodeling immune microenvironment via the PI3K-AKT pathway [J]. J Nanobiotechnology, 2025, 23(1): 41. doi: 10.1186/s12951-025-03096-5 . |
| [8] | FENG J, XIU Q, HUANG Y, et al. Plant-Derived Vesicle-Like Nanoparticles as Promising Biotherapeutic Tools: Present and Future [J]. Adv Mater, 2023, 35(24): e2207826. doi: 10.1002/adma.202207826 . |
| [9] | K?RBA? O K, SA?RA? D, ?IFT?I ? C, et al. Unveiling the potential: Extracellular vesicles from plant cell suspension cultures as a promising source [J]. Biofactors, 2025, 51(1): e2090. doi: 10.1002/biof.2090 . |
| [10] | SONG Y, FENG N, YU Q, et al. Exosomes in Disease Therapy: Plant-Derived Exosome-Like Nanoparticles Current Status, Challenges, and Future Prospects [J]. Int J Nanomedicine, 2025, 20: 10613-10644. doi: 10.2147/IJN.S540094 . |
| [11] | TIWARI A, SONI N, DONGRE S, et al. The role of plant-derived extracellular vesicles in ameliorating chronic diseases [J]. Mol Biol Rep, 2025, 52(1): 360. doi:10.1007/s11033-025- 10466-7 . |
| [12] | KILASONIYA A, GARAEVA L, SHTAM T, et al. Potential of Plant Exosome Vesicles from Grapefruit (Citrus × paradisi) and Tomato (Solanum lycopersicum) Juices as Functional Ingredients and Targeted Drug Delivery Vehicles [J]. Antioxidants (Basel), 2023, 12(4):943. doi: 10.3390/antiox12040943 . |
| [13] | HUANG D, CHEN J, SHEN H, et al. Research Progress and Preclinical Prospects of Plant-Derived Extracellular Vesicles in Targeted Delivery of Antitumor Drugs [J]. Int J Nanomedicine, 2026, 21: 596279. doi: 10.2147/IJN.S596279 . |
| [14] | KIM T, HONG J W, LEE L P. Efficient methods of isolation and purification of extracellular vesicles [J]. Nano Converg, 2025, 12(1): 45. doi: 10.1186/s40580-025-00509-x . |
| [15] | SUANNO C, TONOLI E, FORNARI E, et al. Small extracellular vesicles released from germinated kiwi pollen (pollensomes) present characteristics similar to mammalian exosomes and carry a plant homolog of ALIX [J]. Front Plant Sci, 2023, 14: 1090026. doi: 10.3389/fpls.2023.1090026 . |
| [16] | SHAO M, JIN X, CHEN S, et al. Plant-derived extracellular vesicles -a novel clinical anti-inflammatory drug carrier worthy of investigation [J]. Biomed Pharmacother, 2023, 169: 115904. doi: 10.1016/j.biopha.2023.115904 . |
| [17] | LI S, ZHANG Y, LIU X, et al. Cross-kingdom delivery and putative gene modulation of androgen pathways by plant-derived exosome-like nanoparticles from polygoni multiflori radix promotes hair growth via miRNA cargo [J]. Pharmacological Research, 2025, 222: 108033. doi: 10.1016/j.phrs.2025.108033 . |
| [18] | WANG J, ZHANG T, GU R, et al. Development and Evaluation of Reconstructed Nanovesicles from Turmeric for Multifaceted Obesity Intervention [J]. ACS Nano, 2024, 18(34): 23117-23135. doi: 10.1021/acsnano.4c05309 . |
| [19] | ZHENG Y, QIN Y, HE Q, et al. Enhanced Delivery of Oral Biomacromolecules through Edible Plant-Derived Nanovehicles: Exploiting the Self-Amplifying Trancytosis Feedback Loop and Phosphatidic Acid [J]. ACS Nano, 2026, 20(1): 1710-1731. doi: 10.1021/acsnano.5c20533 . |
| [20] | HAN B, JIANG Y, LIU H, et al. Pueraria lobata-derived exosome-like nanovesicles alleviate rheumatoid arthritis via targeting Ruminococcus gnavus phenylethylamine production [J]. Gut, 2026,75(6):1123-1135. doi: 10.1136/gutjnl-2025-336451 . |
| [21] | IRIAWATI I, VITASASTI S, RAHMADIAN F N A, et al. Isolation and characterization of plant-derived exosome-like nanoparticles from Carica papaya L. fruit and their potential as anti-inflammatory agent [J]. PLoS One, 2024, 19(7): e0304335. doi: 10.1371/journal.pone.0304335 . |
| [22] | 岳进茹, 张育敏, 刘静淑, 等. 独活寄生汤含药血清细胞外囊泡对类风湿关节炎滑膜成纤维细胞的影响 [J]. 中国组织工程研究, 2025, 29(23): 4915-4923. doi: 10.12307/2025.081 . |
| [23] | WANG X, LIU H, FAN H, et al. Ginseng exosomal miRNA ameliorates rheumatoid arthritis by mediating KRAS-MAPK signaling [J]. Int Immunopharmacol, 2025, 161: 115046. doi: 10.1016/j.intimp.2025.115046 . |
| [24] | KOJIMA T, HAYASHI T, KAGEYAMA Y, et al. Exosome-like nanovesicles from Peucedanum Japonicum directly regulate inflammatory cytokines via small RNAs [J]. Sci Rep, 2025, 15(1): 27424. doi: 10.1038/s41598-025-12175-4 . |
| [25] | LIU Y, TAO S, ZHANG Z, et al. Perilla frutescens Leaf-Derived Extracellular Vesicle-Like Particles Carry Pab-miR-396a-5p to Alleviate Psoriasis by Modulating IL-17 Signaling [J]. Research (Wash D C), 2025, 8: 0675. doi: 10.34133/research.0675 . |
| [26] | HUANG R, JIA B, SU D, et al. Plant exosomes fused with engineered mesenchymal stem cell-derived nanovesicles for synergistic therapy of autoimmune skin disorders [J]. J Extracell Vesicles, 2023, 12(10): e12361. doi: 10.1002/jev2.12361 . |
| [27] | RAO Q, MA G, LI M, et al. Targeted delivery of triptolide by dendritic cell-derived exosomes for colitis and rheumatoid arthritis therapy in murine models [J]. Br J Pharmacol, 2023, 180(3): 330-346. doi: 10.1111/bph.15958 . |
| [28] | LIU Q, ZOU J, CHEN Z, et al. Current research trends of nanomedicines [J]. Acta Pharm Sin B, 2023, 13(11): 4391-4416. doi: 10.1016/j.apsb.2023.05.018 . |
| [29] | FU S, YI X, LI Y, et al. Berberine and chlorogenic acid-assembled nanoparticles for highly efficient inhibition of multidrug-resistant Staphylococcus aureus [J]. J Hazard Mater, 2024, 473: 134680. doi: 10.1016/j.jhazmat.2024.134680 . |
| [30] | 沈小兰, 刘小曼, 侯晓强, 等. 黄芩苷抑制类风湿关节炎滑膜炎症机制及临床应用的研究进展 [J]. 实用医学杂志, 2024, 40(22): 3256-3261. doi: 10.3969/j.issn.1006-5725.2024.22.023 . |
| [31] | LI Z, YANG Y, SHI Y, et al. Bioengineered photosynthetic nanothylakoids reshape the inflammatory microenvironment for rheumatoid arthritis therapy [J]. Nat Nanotechnol, 2026, 21(1): 125-139. doi: 10.1038/s41565-025-02063-3 . |
| [32] | SU Y, CHEN R, WANG B, et al. Erythrocyte membrane camouflaged celastrol and bilirubin self-assembly for rheumatoid arthritis immunotherapy based on STING inhibition and RONS clearance [J]. J Nanobiotechnology, 2025, 23(1): 318. doi: 10. 1186/s12951-025-03389-9 . |
| [33] | LIN Y, YI O, HU M, et al. Multifunctional nanoparticles of sinomenine hydrochloride for treat-to-target therapy of rheumatoid arthritis via modulation of proinflammatory cytokines [J]. J Control Release, 2022, 348: 42-56. doi: 10.1016/j.jconrel.2022.05.016 . |
| [34] | HONG J, JI P, AN J, et al. Self-Assembled Myricetin-Arginine Conjugate Nanozymes for Targeted Suppression of Joint Inflammation and Osteoclastogenesis in Rheumatoid Arthritis [J]. Adv Sci (Weinh), 2026, 13(14): e21864. doi: 10.1002/advs. 202521864 . |
/
| 〈 |
|
〉 |