Plant-derived nanovesicles: harnessing nature's power for tissue protection and repair

Abstract

Tissue damage and aging lead to dysfunction, disfigurement, and trauma, posing significant global challenges. Creating a regenerative microenvironment to resist external stimuli and induce stem cell differentiation is essential. Plant-derived nanovesicles (PDNVs) are naturally bioactive lipid bilayer nanovesicles that contain proteins, lipids, ribonucleic acid, and metabolites. They have shown potential in promoting cell growth, migration, and differentiation into various types of tissues. With immunomodulatory, microbiota regulatory, antioxidant, and anti-aging bioactivities, PDNVs are valuable in resisting external stimuli and facilitating tissue repair. The unique structure of PDNVs provides an optimal platform for drug encapsulation, and surface modifications enhance their stability and specificity. Moreover, by employing synergistic administration strategies, PDNVs can maximize their therapeutic potential. This review summarized the progress and prospects of PDNVs as regenerative tools, provided insights into their selection for repair activities based on existing studies, considered the key challenge for clinical application, and anticipated their continued prominent role in the field of biomedicine.

Fig. 1

PDNVs composition and mechanism of action. The recognition and binding of β-glucan from oats-derived nanovesicles and HPCA from microglia [24]; galactose from tea-derived nanovesicles and the C-type galactose receptor from macrophages [43]; and Lectin II from garlic-derived nanovesicles and the CD98 receptor from liver cells [46]. (PDNVs, Plant-derived nanovesicles, ORF, open reading frame, HPCA, hippocampal calcium-binding protein, 3′UTR, 3′ untranslated region, CD98 receptor, cluster of differentiation 98 receptor.)

Fig. 2

The bioactivity of PDNVs in tissue protection and repair. (PDNVs plant-derived nanovesicles, ROS reactive oxygen species.)

Fig. 3

Potential applications of PDNVs in tissue injury repair. A Oats-derived nanovesicles could alleviate inflammation in mouse brain tissue caused by ethanol [24]. (CD control; Eth Ethanol, OatN Oat-derived nanovescicles) B Dendropanax morbifera-derived nanovesicles could reduce melanin formation in human skin tissue [88]. (LEVs, Dendropanax morbifera leaf-derived extracellular vesicles) C Blueberries-derived nanovesicles could alleviate nonalcoholic liver diseases in high-fat diet mouse [54]. (NCD normal chow diet, HFD high-fat diet, BELNs, Blueberries-derived exosomes like nanoparticles) (D) Some key miRNAs in PDNVs could alleviate lung inflammation in a rat model [89]. (Nsp12/13, nonstructural proteins of coronaviruses (including SARS-CoV-2)) E Mulberry bark-derived nanovesicles could alleviate mouse colitis induced by DSS [47]. (PBS, phosphate buffered saline, DSS, dextran sodium sulfate; MBELNs, Mulberry bark-derived exosomes like nanoparticles) F Yam-derived nanovesicles could enhance bone density in ovariectomy-induced osteoporotic mice [19]. (CON control; YNVs Yam-derived nanovesicles, OVX ovariectomy, E2 estradiol)

Fig. 4

The dressing loaded with ginseng-derived nanovesicles promotes nerve regeneration and blood vessel formation in wounds. A The Venn diagram of miRNAs from bone marrow mesenchymal stem cells and G-E. B Scanning electron microscopy image of the dressing loaded with G–E (nanovesicles indicated by red arrows). C The dressing loaded with G–E promotes regeneration of skin appendages. Expression of D CD31 (red, associated with blood vessel formation); E CD90 (red, associated with neuronal migration and synaptogenesis); F Nestin (green, a marker for neural stem cells and neurodevelopment) in the different dressing group. G The wound healing rate among different dressing groups during the healing process. (The lowercase letters c, d, e, f followed by 1, 2, 3, 4 represent the blank group, G-E group, CLD-C group, and CLD-C-E group, respectively.) (G–E, ginseng-derived nanovesicles; CLD-C-E, CXCL12 and G-Exo-loaded cross-linked gel dressing; CXCL12, C-X-C motif chemokine ligand 12; CD cluster of differentiation) (Copyright [20])

Fig. 5

Engineered ginger-derived nanovesicles facilitate synergistic anti-infective therapy [38]. a. Extracellular vesicles (EVs) were obtained from fresh ginger juice through centrifugation, and Pt was conjugated onto Pb, followed by their covalent linkage through amide bonds to form EV-Pb-Pt. b. Intravenous injection of EV-Pb-Pt exhibited several advantages: I. Prolonged blood circulation stability; II. Lipid-dependent uptake; III. Synergistic effects of an electric field and near-infrared (NIR) light at 980 nm, resulting in the generation of reactive oxygen species (ROS) and exhibiting antibacterial effects. (NIR near-Infrared, ROS reactive oxygen species, PA photoacoustic, AC alternating current) (Copyright [38])