Application Progress of Plant-derived Exosome-like Nanoparticles in Diabetic Ulcers
Journal: Journal of Clinical Medicine Research DOI: 10.32629/jcmr.v6i4.4797
Abstract
Diabetes foot ulcers (DFU) is a serious complication of diabetes with high morbidity and mortality. The existing treatment methods have bottlenecks such as large trauma, high cost, and long recovery period. Plant derived extracellular vesicle like nanoparticles (PENPs) have become a novel candidate strategy for DFU treatment due to their natural low immunogenicity, high content of active ingredients such as polyphenols and miRNA, easy large-scale extraction, and good biocompatibility. This article systematically reviews the core mechanisms by which PENPs regulate DFU healing, including exerting anti-inflammatory and antioxidant effects by activating the Nrf2/HO-1 pathway, regulating the gut microbiota immune axis to improve systemic metabolism, promoting angiogenesis through glycolysis reprogramming and PI3K/Akt pathways, regulating insulin signaling to improve glucose metabolism, and directly promoting accelerated proliferation, migration, and re epithelialization of keratinocytes and fibroblasts; Simultaneously reviewing the research progress of 9 types of PENPs, including red onions, lemons, ginseng, and wheat, in cell or animal models, confirming their multi-target healing promoting activity. This article provides theoretical and experimental basis for expanding the field of extracellular vesicle therapy and developing safe and effective natural biological treatment strategies for DFU.
Keywords
diabetes foot ulcer, plant exocrine, extracellular vesicle like nanoparticles
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[24] Azizi F, Shiri E, Azadian Z, et al. Preparation of Allium cepa-derived exosome-like nanovesicles and their anti-inflammatory potential in a skin wound healing mouse model. Mol Biol Rep. 2025;52(1):769. Published 2025 Jul 29. doi:10.1007/s11033-025-10867-8
[25] Kim H, Shin HY, Park M, Ahn K, Kim SJ, An SH. Exosome-Like Vesicles from Lithospermum erythrorhizon Callus Enhanced Wound Healing by Reducing LPS-Induced Inflammation. J Microbiol Biotechnol. 2024;35:e2410022. Published 2024 Nov 28. doi:10.4014/jmb.2410.10022
[26] Daniello V, De Leo V, Lasalvia M, et al. Solanum lycopersicum (Tomato)-Derived Nanovesicles Accelerate Wound Healing by Eliciting the Migration of Keratinocytes and Fibroblasts. Int J Mol Sci. 2024;25(5):2452. Published 2024 Feb 20. doi:10.3390/ijms25052452
[27] Tan S, Liu Z, Cong M, et al. Dandelion-derived vesicles-laden hydrogel dressings capable of neutralizing Staphylococcus aureus exotoxins for the care of invasive wounds. J Control Release. 2024;368:355-371. doi:10.1016/j.jconrel.2024.02.045
[28] Wu B, Pan W, Luo S, et al. Turmeric-Derived Nanoparticles Functionalized Aerogel Regulates Multicellular Networks to Promote Diabetic Wound Healing. Adv Sci (Weinh). 2024;11(18):e2307630. doi:10.1002/advs.202307630
[2] Armstrong DG, Tan TW, Boulton AJM, Bus SA. Diabetic Foot Ulcers: A Review. JAMA. 2023;330(1):62-75. doi:10.1001/jama.2023.10578
[3] Wang F, Yao J, Zuo H, Jiao Y, Wu J, Meng Z. Diverse-Origin Exosomes Therapeutic Strategies for Diabetic Wound Healing. Int J Nanomedicine. 2025;20:7375-7402. Published 2025 Jun 12. doi:10.2147/IJN.S519379
[4] Yi J, Tang Q, Sun S, Xie H, Wang L, Yin X. Exosomes in Diabetic Wound Healing: Mechanisms, Applications, and Perspectives. Diabetes Metab Syndr Obes. 2025;18:2955-2976. Published 2025 Aug 21. doi:10.2147/DMSO.S532885
[5] He C, Wang K, Xia J, et al. Natural exosomes-like nanoparticles in mung bean sprouts possesses anti-diabetic effects via activation of PI3K/Akt/GLUT4/GSK-3β signaling pathway. J Nanobiotechnology. 2023;21(1):349. Published 2023 Sep 28. doi:10.1186/s12951-023-02120-w
[6] Gieroba B, Kryska A, Sroka-Bartnicka A. Type 2 diabetes mellitus — conventional therapies and future perspectives in innovative treatment. Biochem Biophys Rep. 2025;42:102037. Published 2025 May 2. doi:10.1016/j.bbrep.2025.102037
[7] Kumar A, Sundaram K, Teng Y, et al. Ginger nanoparticles mediated induction of Foxa2 prevents high-fat diet-induced insulin resistance. Theranostics. 2022;12(3):1388-1403. Published 2022 Jan 1. doi:10.7150/thno.62514
[8] Wang X, Tian R, Liang C, et al. Biomimetic nanoplatform with microbiome modulation and antioxidant functions ameliorating insulin resistance and pancreatic β-cell dysfunction for T2DM management. Biomaterials. 2025;313:122804. doi:10.1016/j.biomaterials.2024.122804
[9] Jin E, Yang Y, Cong S, et al. Lemon-derived nanoparticle-functionalized hydrogels regulate macrophage reprogramming to promote diabetic wound healing. J Nanobiotechnology. 2025;23(1):68. Published 2025 Jan 31. doi:10.1186/s12951-025-03138-y
[10] Sundaram K, Teng Y, Mu J, et al. Outer Membrane Vesicles Released from Garlic Exosome-like Nanoparticles (GaELNs) Train Gut Bacteria that Reverses Type 2 Diabetes via the Gut-Brain Axis. Small. 2024;20(20):e2308680. doi:10.1002/smll.202308680
[11] Li D, Yi G, Cao G, et al. Dual-Carriers of Tartary Buckwheat-Derived Exosome-Like Nanovesicles Synergistically Regulate Glucose Metabolism in the Intestine-Liver Axis. Small. 2025;21(16):e2410124. doi:10.1002/smll.202410124
[12] Zou J, Song Q, Shaw PC, Wu Y, Zuo Z, Yu R. Tangerine Peel-Derived Exosome-Like Nanovesicles Alleviate Hepatic Steatosis Induced by Type 2 Diabetes: Evidenced by Regulating Lipid Metabolism and Intestinal Microflora. Int J Nanomedicine. 2024;19:10023-10043. Published 2024 Sep 30. doi:10.2147/IJN.S478589
[13] Teng Y, Ren Y, Sayed M, et al. Plant-Derived Exosomal MicroRNAs Shape the Gut Microbiota. Cell Host Microbe. 2018;24(5):637-652.e8. doi:10.1016/j.chom.2018.10.001
[14] Tan M, Liu Y, Xu Y, et al. Plant-Derived Exosomes as Novel Nanotherapeutics Contrive Glycolysis Reprogramming-Mediated Angiogenesis for Diabetic Ulcer Healing. Biomater Res. 2024;28:0035. Published 2024 Jun 5. doi:10.34133/bmr.0035
[15] Savcı Y, Kırbaş OK, Bozkurt BT, et al. Grapefruit-derived extracellular vesicles as a promising cell-free therapeutic tool for wound healing. Food Funct. 2021;12(11):5144-5156. doi:10.1039/d0fo02953j
[16] Şahin F, Koçak P, Güneş MY, Özkan İ, Yıldırım E, Kala EY. In Vitro Wound Healing Activity of Wheat-Derived Nanovesicles. Appl Biochem Biotechnol. 2019;188(2):381-394. doi:10.1007/s12010-018-2913-1
[17] Yang S, Lu S, Ren L, et al. Ginseng-derived nanoparticles induce skin cell proliferation and promote wound healing. J Ginseng Res. 2023;47(1):133-143. doi:10.1016/j.jgr.2022.07.005
[18] Kim MK, Choi YC, Cho SH, Choi JS, Cho YW. The Antioxidant Effect of Small Extracellular Vesicles Derived from Aloe vera Peels for Wound Healing. Tissue Eng Regen Med. 2021;18(4):561-571. doi:10.1007/s13770-021-00367-8
[19] Kim M, Park JH. Isolation of Aloe saponaria-Derived Extracellular Vesicles and Investigation of Their Potential for Chronic Wound Healing. Pharmaceutics. 2022;14(9):1905. Published 2022 Sep 8. doi:10.3390/pharmaceutics14091905
[20] Ramírez O, Pomareda F, Olivares B, et al. Aloe vera peel-derived nanovesicles display anti-inflammatory properties and prevent myofibroblast differentiation. Phytomedicine. 2024;122:155108. doi:10.1016/j.phymed.2023.155108
[21] Liao Q, Su L, Pang L, et al. Natural exosome-like nanoparticles derived from ancient medicinal insect Periplaneta americana L. as a novel diabetic wound healing accelerator. J Nanobiotechnology. 2023;21(1):169. Published 2023 May 26. doi:10.1186/s12951-023-01923-1
[22] Feng H, Yue Y, Zhang Y, et al. Plant-Derived Exosome-Like Nanoparticles: Emerging Nanosystems for Enhanced Tissue Engineering. Int J Nanomedicine. 2024;19:1189-1204. Published 2024 Feb 7. doi:10.2147/IJN.S448905
[23] Cai H, Huang LY, Hong R, et al. Momordica charantia Exosome-Like Nanoparticles Exert Neuroprotective Effects Against Ischemic Brain Injury via Inhibiting Matrix Metalloproteinase 9 and Activating the AKT/GSK3β Signaling Pathway. Front Pharmacol. 2022;13:908830. Published 2022 Jun 24. doi:10.3389/fphar.2022.908830
[24] Azizi F, Shiri E, Azadian Z, et al. Preparation of Allium cepa-derived exosome-like nanovesicles and their anti-inflammatory potential in a skin wound healing mouse model. Mol Biol Rep. 2025;52(1):769. Published 2025 Jul 29. doi:10.1007/s11033-025-10867-8
[25] Kim H, Shin HY, Park M, Ahn K, Kim SJ, An SH. Exosome-Like Vesicles from Lithospermum erythrorhizon Callus Enhanced Wound Healing by Reducing LPS-Induced Inflammation. J Microbiol Biotechnol. 2024;35:e2410022. Published 2024 Nov 28. doi:10.4014/jmb.2410.10022
[26] Daniello V, De Leo V, Lasalvia M, et al. Solanum lycopersicum (Tomato)-Derived Nanovesicles Accelerate Wound Healing by Eliciting the Migration of Keratinocytes and Fibroblasts. Int J Mol Sci. 2024;25(5):2452. Published 2024 Feb 20. doi:10.3390/ijms25052452
[27] Tan S, Liu Z, Cong M, et al. Dandelion-derived vesicles-laden hydrogel dressings capable of neutralizing Staphylococcus aureus exotoxins for the care of invasive wounds. J Control Release. 2024;368:355-371. doi:10.1016/j.jconrel.2024.02.045
[28] Wu B, Pan W, Luo S, et al. Turmeric-Derived Nanoparticles Functionalized Aerogel Regulates Multicellular Networks to Promote Diabetic Wound Healing. Adv Sci (Weinh). 2024;11(18):e2307630. doi:10.1002/advs.202307630
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