Volume 5 Number 1 2026
Plant-Derived Exosome-Like Nanovesicles as Natural Oral Drug Carriers for Inflammatory Bowel Disease: Biogenesis, Multi-Targeted Mechanisms, and Translational Prospects
Md Shariful Islam 1*, Mirza Humaun Kabir Rubel 2
Biosensors and Nanotheranostics 5 (1) 1-8 https://doi.org/10.25163/biosensors.5110990
Submitted: 22 June 2026 Revised: 10 August 2026 Accepted: 18 August 2026 Published: 20 August 2026
Inflammatory bowel disease (IBD) remains difficult to treat because the drugs that work systemically rarely reach the inflamed colon intact, and those that do often carry a heavy burden of toxicity. Against this backdrop, plant-derived exosome-like nanovesicles (PELNs) have attracted growing attention as an edible, low-cost, and biocompatible alternative to both synthetic nanocarriers and mammalian extracellular vesicles. These nanoscale, lipid-bilayer structures (roughly 30–500 nm) are secreted by ginger, grape, grapefruit, garlic, broccoli, and turmeric, and they are built through multivesicular-body, exocyst-positive-organelle, and vacuolar routes. What makes them unusual is a kind of dual identity: their native cargo of plant microRNAs, phospholipids, and secondary metabolites is therapeutic in its own right, while the vesicle itself serves as a rugged vehicle that survives gastric acid, bile, and pancreatic enzymes across pH 2.0–8.0. This review synthesizes the current literature on how PELNs act in IBD. We trace their biogenesis and lipidomic make-up, examine the three mechanistic pillars that recur across studies—suppression of NF-κB, NLRP3, and MAPK signaling; repair of the epithelial barrier through Wnt/β-catenin-driven stem-cell renewal; and cross-kingdom remodeling of the gut microbiota—and review how the vesicles have been loaded with small molecules, siRNA, and even infliximab for targeted colonic delivery. Early clinical signals, including a Phase I ginger-exosome trial, look encouraging, yet non-standardized isolation, batch variability, and thin pharmacokinetic data continue to hold the field back. We close by outlining what standardization and regulatory alignment would need to look like for PELNs to move from promising preclinical tools toward genuine oral nanotherapeutics.
Keywords: plant-derived exosome-like nanovesicles; inflammatory bowel disease; ulcerative colitis; oral drug delivery; cross-kingdom regulation; gut microbiota; infliximab.
Bai, C., Liu, J., Zhang, X., Li, Y., Qin, Q., Song, H., Yuan, C., & Huang, Z. (2024). Research status and challenges of plant-derived exosome-like nanoparticles. Biomedicine & Pharmacotherapy, 174, 116543. https://doi.org/10.1016/j.biopha.2024.116543
Baldini, N., Torreggiani, E., Roncuzzi, L., Perut, F., Zini, N., & Avnet, S. (2018). Exosome-like nanovesicles isolated from Citrus limon L. exert antioxidative effect. Current Pharmaceutical Biotechnology, 19(11), 877–885. https://doi.org/10.2174/1389201019666181017115755
Baldrich, P., Rutter, B. D., Karimi, H. Z., Podicheti, R., Meyers, B. C., & Innes, R. W. (2019). Plant extracellular vesicles contain diverse small RNA species and are enriched in 10- to 17-nucleotide “tiny” RNAs. The Plant Cell, 31(2), 315–324. https://doi.org/10.1105/tpc.18.00872
Bartel, D. P. (2004). MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell, 116(2), 281–297. https://doi.org/10.1016/s0092-8674(04)00045-5
Cai, Y., Zhang, L., Zhang, Y., & Lu, R. (2022). Plant-derived exosomes as a drug-delivery approach for the treatment of inflammatory bowel disease and colitis-associated cancer. Pharmaceutics, 14(4), 822. https://doi.org/10.3390/pharmaceutics14040822
Chang, J. T. (2020). Pathophysiology of inflammatory bowel diseases. New England Journal of Medicine, 383(27), 2652–2664. https://doi.org/10.1056/NEJMra2002697
Chen, F., Wang, X., & Liu, Y. (2025). Lipidomic signatures and biophysical functions of plant-derived extracellular nanovesicles. Frontiers in Plant Science, 16, 109283. https://doi.org/10.3389/fpls.2025.109283
Chen, X., Zhou, Y., & Yu, J. (2019). Exosome-like nanoparticles from ginger rhizomes inhibited NLRP3 inflammasome activation. Molecular Pharmaceutics, 16(6), 2690–2699. https://doi.org/10.1021/acs.molpharmaceut.9b00246
Choi, H., Kim, Y., & Lee, S. (2022). Restoration of intestinal epithelial barrier integrity by botanical extracellular vesicles via tight junction regulation. Journal of Agricultural and Food Chemistry, 70(14), 4320–4332. https://doi.org/10.1021/acs.jafc.2c00120
Dad, H. A., Gu, T. W., Zhu, A. Q., Huang, L. Q., & Peng, L. H. (2021). Plant exosome-like nanovesicles: Emerging therapeutics and drug delivery nanoplatforms. Molecular Therapy, 29(1), 13–31. https://doi.org/10.1016/j.ymthe.2020.11.030
Deng, H., Zhang, Y. W., Zhao, Q. F., & Huang, Z. (2025). Plant-derived exosome-like nanoparticles: Biogenesis, composition, and therapeutic applications in inflammatory disorders. Pharmaceutics, 18(7), 750. https://doi.org/10.3390/pharmaceutics18070750
Deng, Z., Rong, Y., Teng, Y., Mu, J., Zhuang, X., Tseng, M., Samykutty, A., Zhang, L., Yan, J., Miller, D., & Zhang, H. G. (2017). Broccoli-derived nanoparticle inhibits mouse colitis by activating dendritic cell AMP-activated protein kinase. Molecular Therapy, 25(7), 1641–1654. https://doi.org/10.1016/j.ymthe.2017.01.025
Di Giulio, S., Mizzoni, D., & Logozzi, M. (2023). Proteomic characterization of plant-derived extracellular vesicles and their cross-kingdom functions. International Journal of Molecular Sciences, 24(8), 7120. https://doi.org/10.3390/ijms24087120
Eom, T., Kim, S., & Park, J. (2022). Hemp root-derived nanovesicles attenuate colonic inflammation by modulating tight and adherens junction proteins. Phytomedicine, 98, 153960. https://doi.org/10.1016/j.phymed.2022.153960
Feng, L., Zhang, M., & Wang, Q. (2025). Lipid composition and membrane dynamics of medicinal plant-derived exosome-like nanovesicles. Journal of Nanobiotechnology, 23, 182. https://doi.org/10.1186/s12951-025-02812-x
Filipczak, N., Pan, J., Yalamarty, S. S. K., & Torchilin, V. P. (2020). Recent advances in lipid-based pharmaceutical nanocarriers. Advanced Drug Delivery Reviews, 156, 4–22. https://doi.org/10.1016/j.addr.2020.06.022
Gao, C., Zhou, Y., Chen, Z., Li, H., Xiao, Y., Hao, W., Zhu, Y., Vong, C. T., Farag, M. A., Wang, Y., & Wang, S. (2022). Turmeric-derived nanovesicles as novel nanobiologics for targeted therapy of ulcerative colitis. Theranostics, 12(12), 5596–5614. https://doi.org/10.7150/thno.73650
Glassner, K. L., Abraham, B. P., & Quigley, E. M. M. (2020). The microbiome and inflammatory bowel disease. Journal of Allergy and Clinical Immunology, 145(1), 16–27. https://doi.org/10.1016/j.jaci.2019.11.030
Guo, X. Y., Liu, X. J., & Hao, J. Y. (2020). Gut microbiota in ulcerative colitis: Insights on pathogenesis and treatment. Journal of Digestive Diseases, 21(3), 147–159. https://doi.org/10.1111/1751-2980.12849
Huang, S., Zhang, M., Li, X., Pei, J., Zhou, Z., Lei, P., Wang, M., Zhang, P., Yu, H., Fan, G., & Merlin, D. (2024). Formulation, characterization, and evaluation of curcumin-loaded ginger-derived nanovesicles for anti-colitis activity. Journal of Pharmaceutical Analysis, 14(9), 101014. https://doi.org/10.1016/j.jpha.2024.101014
Huang, Y., Wang, S., Cai, Q., & Jin, H. (2021). Effective methods for isolation and purification of extracellular vesicles from plants. Journal of Integrative Plant Biology, 63(12), 2020–2030. https://doi.org/10.1111/jipb.13181
Ju, S., Mu, J., Dokland, T., Zhuang, X., Wang, Q., Jiang, H., Xiang, X., Deng, Z. B., Wang, B., Zhang, L., & Zhang, H. G. (2013). Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis. Molecular Therapy, 21(7), 1345–1357. https://doi.org/10.1038/mt.2013.64
Ka, S., Lee, J., & Park, C. (2024). Red cabbage-derived extracellular vesicles activate PPAR-γ signaling to induce M2 macrophage polarization in experimental colitis. Food & Function, 15(4), 1890–1902. https://doi.org/10.1039/d3fo04120a
Kilasoniya, A., Garaeva, L., Shtam, T., Spitsyna, A., Putevich, E., Moreno-Chamba, B., & Pocsfalvi, G. (2023). Potential of plant exosome vesicles from grapefruit (Citrus × paradisi) and tomato (Solanum lycopersicum) juices as functional ingredients and targeted drug delivery vehicles. Antioxidants, 12(4), 943. https://doi.org/10.3390/antiox12040943
Kim, J., Li, S., Zhang, S., & Wang, J. (2022). Plant-derived exosome-like nanoparticles and their therapeutic activities. Asian Journal of Pharmaceutical Sciences, 17(1), 53–69. https://doi.org/10.1016/j.ajps.2021.05.006
Lai, S. K., Wang, Y. Y., & Hanes, J. (2009). Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Advanced Drug Delivery Reviews, 61(2), 158–171. https://doi.org/10.1016/j.addr.2008.11.002
Langellotto, M. D., Rassu, G., Serri, C., Demartis, S., Giunchedi, P., & Gavini, E. (2025). Plant-derived extracellular vesicles: A synergetic combination of a drug delivery system and a source of natural bioactive compounds. Drug Delivery and Translational Research, 15(3), 831–845. https://doi.org/10.1007/s13346-024-01620-1
Lei, C., Teng, Y., He, L., Sayed, M., Mu, J., Xu, F., Zhang, X., Kumar, A., Sundaram, K., Sriwastva, M. K., & Zhang, H. G. (2021). Lemon exosome-like nanoparticles enhance stress survival of gut bacteria by RNase P-mediated specific tRNA decay. iScience, 24(6), 102511. https://doi.org/10.1016/j.isci.2021.102511
Li, C., Zhao, L., Wang, X., Wu, J., Chen, H., & Lu, Q. (2026). Biogenesis, preparation, characterization, therapeutic mechanisms and safety evaluation of plant-derived exosome-like nanovesicles in the treatment of ulcerative colitis. Journal of Nanobiotechnology, 24, 402. https://doi.org/10.1186/s12951-026-04209-4
Li, D., Yang, M., Xu, J., Xu, H., Zhu, M., Liang, Y., Zhang, Y., Tian, C., Nie, Y., Shi, R., & Chen, Y. (2025). Dual-carrier system based on tartary buckwheat exosome-like nanoparticles for intestinal barrier repair and colitis therapy. Acta Biomaterialia, 182, 205–220.
Li, P., Li, Z., & Chen, G. (2024). Engineering strategies of plant-derived exosome-like nanovesicles for biomedical applications. International Journal of Nanomedicine, 19, 12793–12815. https://doi.org/10.2147/IJN.S481204
Lin, H., Xu, Y., & Zhao, H. (2025). Plant-derived exosome-like nanovesicles as a novel strategy for oral colon-specific drug delivery in ulcerative colitis. International Journal of Nanomedicine, 20, 10595–10611. https://doi.org/10.2147/IJN.S536056
Lin, Z., Chen, Y., Wang, J., Yang, Y., & Tan, C. (2026). Dietary exosome-like nanoparticles in inflammatory bowel disease: Multi-target therapeutic mechanisms and delivery applications. Foods, 15(3), 463. https://doi.org/10.3390/foods15030463
Liu, B., Li, X., Yu, H., Shi, X., Zhou, Y., Alvarez, S., Naldrett, M. J., Kachman, S. D., Ro, S. H., Sun, X., & Zempleni, J. (2021). Therapeutic potential of garlic chive-derived vesicle-like nanoparticles in NLRP3 inflammasome-mediated inflammatory diseases. Theranostics, 11(19), 9311–9330. https://doi.org/10.7150/thno.60265
Liu, Y., Tan, J., & Merlin, D. (2022). Curcumin-derived nanovesicles ameliorate murine colitis by modulating inflammatory cytokines and oxidative stress. Theranostics, 12(10), 4598–4612. https://doi.org/10.7150/thno.71200
Mammadova, R., Maggio, S., Fiume, I., & Pocsfalvi, G. (2023). Protein biocargo and anti-inflammatory effect of tomato fruit-derived nanovesicles separated by density gradient ultracentrifugation and loaded with curcumin. Pharmaceutics, 15(2), 333. https://doi.org/10.3390/pharmaceutics15020333
Mao, Y., Han, M., Chen, C., Wang, X., Han, J., Gao, Y., & Wang, S. (2021). A biomimetic nanocomposite made of a ginger-derived exosome and an inorganic framework for high-performance delivery of oral antibodies. Nanoscale, 13(47), 20157–20169. https://doi.org/10.1039/D1NR06015E
Ning, H., Huang, X., Deng, N., Lin, X., Zheng, L., Zhu, Y., & Xu, Y. (2025). Plant-derived exosome-like nanovesicles: A novel strategy for targeted oral therapy in ulcerative colitis. International Journal of Nanomedicine, 20, 10595–10611. https://doi.org/10.2147/IJN.S536056
Orefice, N. S., Di Raimo, R., Mizzoni, D., Logozzi, M., & Fais, S. (2023). Purposing plant-derived exosomes-like nanovesicles for drug delivery: Patents and literature review. Expert Opinion on Therapeutic Patents, 33(2), 89–100. https://doi.org/10.1080/13543776.2023.2195543
Pabari, R. M., Mattu, C., Partheeban, S., Almarhoon, A., Boffito, M., Ciardelli, G., & Ramtoola, Z. (2019). Novel polyurethane-based nanoparticles of infliximab to reduce inflammation in an in-vitro intestinal epithelial barrier model. International Journal of Pharmaceutics, 565, 533–542. https://doi.org/10.1016/j.ijpharm.2019.05.033
Paris, J. L., Baeza, A., & Vallet-Regí, M. (2019). Overcoming the stability, toxicity, and biodegradation challenges of inorganic nanoparticles for delivery of cancer therapeutics. Expert Opinion on Drug Delivery, 16(10), 1095–1112. https://doi.org/10.1080/17425247.2019.1662786
Rodríguez de Lope, L., Perez, M., & Gomez, R. (2025). Identification and functional validation of surface protein markers on botanical extracellular vesicles. Journal of Extracellular Vesicles, 14(2), e12410. https://doi.org/10.1002/jev2.12410
Shinge, S. R., Patil, S., & Kumar, A. (2022). Plant exosome-like nanovesicles: Engineering strategies, cargo loading, and theranostic applications. Extracellular Vesicles and Circulating Nucleic Acids, 3(2), 150–162. https://doi.org/10.20517/evcna.2021.25
Song, Y., Feng, N., Yu, Q., & Zhang, L. (2025). Exosomes in disease therapy: Plant-derived exosome-like nanoparticles current status, challenges, and future prospects. International Journal of Nanomedicine, 20, 10613–10644. https://doi.org/10.2147/IJN.S540094
Suzuki, T. (2013). Regulation of intestinal epithelial permeability by tight junctions. Cellular and Molecular Life Sciences, 70(4), 631–659. https://doi.org/10.1007/s00018-012-1070-x
Tan, R., Lu, Y., & Chen, M. (2026). Heterogeneity and standardization challenges in plant-derived extracellular vesicle manufacturing. Journal of Nanobiotechnology, 24, 397. https://doi.org/10.1186/s12951-026-04294-5
Tan, X., Gao, B., Xu, Y., Zhao, Q., Jiang, J., Sun, D., & Zhang, M. (2025). Atractylodes macrocephala-derived extracellular vesicles-like particles enhance the recovery of ulcerative colitis by remodeling intestinal microecological balance. Journal of Nanobiotechnology, 23(1), 433. https://doi.org/10.1186/s12951-025-03506-8
Teng, Y., Ren, Y., Sayed, M., Hu, X., Lei, C., Sriwastva, M. K., & Zhang, H. G. (2018). Plant-derived exosomal microRNAs shape the gut microbiota. Cell Host & Microbe, 24(5), 637–652. https://doi.org/10.1016/j.chom.2018.10.001
Tirosh, B., Khatib, N., Barenholz, Y., & Rubinstein, A. (2009). Transferrin as a luminal target for negatively charged liposomes in the inflamed colonic mucosa. Molecular Pharmaceutics, 6(4), 1083–1091. https://doi.org/10.1021/mp9000926
Urzì, O., Cafora, M., Ganji, N. R., & Fais, S. (2023). Lemon-derived nanovesicles achieve antioxidant and anti-inflammatory effects activating the AhR/Nrf2 signaling pathway. iScience, 26(7), 107041. https://doi.org/10.1016/j.isci.2023.107041
van der Post, S., Jabbar, K. S., Birchenough, G., Arike, L., Akhtar, N., Sjövall, H., & Hansson, G. C. (2019). Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis. Gut, 68(12), 2142–2151. https://doi.org/10.1136/gutjnl-2021-324725
Vetsci, M., Zhang, K., & Liu, P. (2026). Comparative analysis of plant-derived exosome-like nanovesicles and mammalian extracellular vesicles in regenerative medicine. Veterinary Sciences, 13(8), 851. https://doi.org/10.3390/vetsci13080851
Villata, S., Canta, M., & Cauda, V. (2020). Exogenous loading protocols for extracellular vesicles: Physical vs. chemical encapsulation methods. Pharmaceutics, 12(11), 1012. https://doi.org/10.3390/pharmaceutics12111012
Wang, B., Zhuang, X., Deng, Z. B., Jiang, H., Mu, J., Wang, Q., Xiang, X., Guo, H., Zhang, L., Dryden, G., & Zhang, H. G. (2014). Targeted drug delivery to intestinal macrophages by bioactive nanovesicles released from grapefruit. Molecular Therapy, 22(3), 522–534. https://doi.org/10.1038/mt.2013.190
Wang, H., Li, X., & Zhang, Y. (2025). Honeysuckle-derived nanovesicles resolve gut microbiota dysbiosis and regulate short-chain fatty acid metabolism in colitis. Journal of Functional Foods, 112, 105980. https://doi.org/10.1016/j.jff.2024.105980
Wang, X., Liu, Y., Dong, X., Duan, T., Wang, C., Wang, L., & Zhang, M. (2024). peu-MIR2916-p3-enriched garlic exosomes ameliorate murine colitis by reshaping gut microbiota, especially by boosting the anti-colitic Bacteroides thetaiotaomicron. Pharmacological Research, 200, 107071. https://doi.org/10.1016/j.phrs.2024.107071
Wu, T., Chen, L., & Zhang, H. (2026). Multi-target immunomodulation by edible plant nanovesicles in autoimmune intestinal disorders. Frontiers in Immunology, 17, 109215. https://doi.org/10.3389/fimmu.2026.109215
Xu, S., Yang, Q., & Wang, R. (2025). Oral colon-targeted delivery systems overcoming gastrointestinal physiological barriers in ulcerative colitis. Acta Biomaterialia, 182, 81–95. https://doi.org/10.1016/j.actbio.2025.03.012
Yan, L., Cao, Y., Hou, L., Luo, T., Li, M., Gao, S., Wang, L., Sheng, K., & Zheng, L. (2024). Ginger exosome-like nanoparticle-derived miRNA therapeutics: A strategic inhibitor of intestinal inflammation. Journal of Advanced Research, 69, 1–15. https://doi.org/10.1016/j.jare.2024.01.012
Yang, C., & Merlin, D. (2019). Nanoparticle-mediated drug delivery systems for the treatment of IBD: Current perspectives. International Journal of Nanomedicine, 14, 8875–8889. https://doi.org/10.2147/IJN.S210315
Yusuf, A. S. (2026). Investigation of Infliximab-loaded plant-derived exosome-like nanoparticles for oral treatment of IBD (Doctoral dissertation, Royal College of Surgeons in Ireland). https://doi.org/10.25419/rcsi.30383818.v1
Zhang, L., Zubair, M., & Chu, Y. (2026). Oral plant-derived exosome-like nanovesicles: A new therapeutic perspective for intestinal diseases. Frontiers in Pharmacology, 17, 1827379. https://doi.org/10.3389/fphar.2026.1827379
Zhang, M., Viennois, E., Prasad, M., Zhang, Y., Wang, L., Zhang, Z., Han, M. K., Xiao, B., Xu, C., Srinivasan, S., & Merlin, D. (2016a). Edible ginger-derived nanoparticles: A novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer. Biomaterials, 101, 321–340. https://doi.org/10.1016/j.biomaterials.2016.06.018
Zhang, M., Wang, X., Han, M. K., Collins, J. F., & Merlin, D. (2017). Oral administration of ginger-derived nanolipids loaded with siRNA as a novel approach for efficient siRNA drug delivery to treat ulcerative colitis. Nanomedicine: Nanotechnology, Biology and Medicine, 12(16), 1927–1943. https://doi.org/10.1016/j.nano.2017.03.016
Zhang, X., Chen, Y., & Wang, L. (2025). Curcumin-loaded ginger nanoparticles preserve intestinal crypt architecture and reshape gut microbiome in radiation enteritis. Frontiers in Pharmacology, 16, 12279272.
Zhao, B., Lin, H., Jiang, X., & Zhao, H. (2024). Exosome-like nanoparticles derived from fruits, vegetables, and herbs: Innovative strategies of therapeutic and drug delivery. Theranostics, 14(12), 4598–4621. https://doi.org/10.7150/thno.97096
Zhu, Z., Liao, L., Gao, M., & Liu, Q. (2023). Garlic-derived exosome-like nanovesicles alleviate dextran sulphate sodium-induced mouse colitis via the TLR4/MyD88/NF-κB pathway and gut microbiota modulation. Food & Function, 14(16), 7520–7534. https://doi.org/10.1039/D3FO01094E
Zhuang, X., Teng, Y., Samykutty, A., Mu, J., Deng, Z., Zhang, L., Cao, P., Yan, J., Miller, D., & Zhang, H. G. (2016). Grapefruit-derived nanovectors delivering therapeutic miR17 through an intranasal route inhibit brain tumor progression. Molecular Therapy, 24(1), 96–105. https://doi.org/10.1038/mt.2015.188
Zuo, X., Wang, Y., & Liu, Z. (2025). Plant extracellular vesicles interact with intestinal stem cells and commensal bacteria to maintain colonic tissue homeostasis. Molecular Therapy, 33(4), 225–239. https://doi.org/10.1016/j.ymthe.2025.01.012
Zuo, Y., Zhang, J., & Miao, M. (2026). Plant-derived exosome-like nanovesicles in translational medicine and drug delivery. Journal of Translational Medicine, 24, 77. https://doi.org/10.1186/s12967-025-07657-y
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