What's the Potential of PELN in Disease Treatment?

Plant-derived exosome-like nanovesicles (PELN) also known as plant-derived extracellular-like vesicles (PELNV) or plant exosome nanovesicles (PEN), exhibit similarities in size, surface charge, and morphology to mammalian-derived exosomes (MDE). These are biological nanostructures that have sparked great interest in the field of nanomedicine in the last decade. PELN are enriched with a variety of biomolecules, such as RNA, proteins and lipids involved in physiological processes and disease treatment. And due to their high biocompatibility and low cytotoxicity, PELN are considered ideal drug delivery systems. These naturally extracted nanoparticles from plants have become a research hotspot due to their unique biological properties and therapeutic potential.

Composition of PELNs

• Lipid bilayer: The lipid bilayer of PELN primarily consists of phosphatidic acid, phosphatidylcholine, digalactosyldiacylglycerol, and monogalactosyldiacylglycerol. These lipid components provide unique biological activity and cell-targeting capabilities. In contrast, the lipid bilayer of animal-derived exosomes mainly contains cholest erol, glycolipids, ceramides, and phosphatidylserine, highlighting distinct differences.
• Proteins: Compared to animal-derived exosomes, PELN have fewer types of proteins identified so far. Some animal-derived exosomes (ADE) feature over 1000 distinct proteins, whereas citrus PERN have identified approximately 600-800 proteins, lemon ELNs contain 243 proteins, and grape ELN have detected only 28 proteins. These primarily include membrane proteins, ribosomal proteins, and enzymes involved in various biological processes.
• Nucleic acid components: Nucleic acids in PELN, especially microRNAs (miRNA), play roles in regulating gene expression and cellular behavior.
• Bioactive Substances: PELN contain numerous plant bioactive substances, such as vitamin C, polyphenols, flavonoids, and carotenoids. These substances can exert multiple effects, including anti-inflammatory, anti-cancer, antibacterial, and antioxidant activities.

Fig. 1. Composition of PELNs (Bai C, Liu J, et al., 2024).

Applications in Disease Treatment

Fig. 2. Overview of biological functions of PELN from a variety of plant sources and their translation into therapeutic applications (Dad HA, Gu TW, et al., 2020).

Gut disease treatment:

In gut diseases, PELN can enhance gut microecological balance and regulate immune responses. For instance, grape ELN alleviate dextran sulfate sodium (DSS)-induced colitis in mice by promoting intestinal stem cell proliferation and mucosal epithelial regeneration to restore gut structure. Moreover, broccoli-derived nanoparticles (BDN) have preventive and therapeutic effects on colitis by maintaining the intestinal immune environment through AMPK activation.

Cancer treatment:

PELN are primarily applied in tumor treatment for drug delivery and targeted therapy. Lemon-derived ELN restrain the growth of chronic myeloid leukaemia (CML) models and reduce angiogenesis-related cytokine secretion through TRAIL-mediated cell death. Ginger ELNs exhibit cytotoxic effects on various tumor cells, including lung carcinoma cells, glioma cells, breast cancer cells, and colon cancer cells.

Tissue repair and regeneration:

PELN can promote tissue repair and regeneration by secreting growth factors and cytokines that facilitate endogenous stem cell proliferation and differentiation. For instance, grape ELN induced proliferation of intestinal stem cells and regeneration of intestinal epithelial tissue, up-regulated the expression of pluripotent stem cell-related factors, and promoted tissue homeostasis.

Alcohol-induced liver injury:

PLEN helps to protect the liver against alcohol-induced injury by reducing liver inflammation and fibrosis. For example, ginger-derived ELN showed increased expression of detoxification/antioxidant genes, reduced lipid droplets in the liver, lowered hepatic triglyceride levels and liver weight, and protected the liver from alcohol-induced injury.

Respiratory diseases:

In treatments of respiratory diseases, it can reduce inflammation in the respiratory tract and boost lung function. For example, honeysuckle-derived exosomes containing miR-2911 can bind to multiple sites in the SARS-CoV-2 genome and significantly inhibit viral replication.

Neurological diseases:

In the treatment of respiratory disorders, PELN reduce respiratory inflammation and improve lung function. For example, grapefruit-derived ELN, when loaded with the anticancer drug doxorubicin into heparin-based nanoparticles, can bypass the blood-brain barrier, accurately transporting doxorubicin to glioma tumors.

Endocrine system diseases:

PELN has shown anti-obesity effects in the treatment of endocrine system disorders, showing potential to regulate blood glucose and improve metabolic status. For instance, ELN of ginger can reduce intracellular lipid accumulation and inhibit the expression of genes related to adipogenesis.

Genitourinary system diseases:

PELN can alleviate inflammation and promote tissue repair. miR159 in PELN is negatively correlated with breast cancer progression, and oral administration of its synthetic miRNA mimics can inhibit tumor cell proliferation.

Cardiovascular diseases:

PELN have the prospect in treatment against cardiovascular diseases, with antioxidative effects and myocardial cell protection. Ziziphus jujuba ELN are used in myocardial ischemia models. The results showed that these vesicles significantly reduced oxidative stress in cardiomyocytes, improved myocardial function, and decreased the rate of apoptosis in cardiomyocytes, demonstrating their promising application in the prevention and treatment of cardiovascular diseases.

PELN have huge potential for a variety of disease treatments: cancer or inflammatory diseases, cardiovascular diseases, neurodegenerative diseases or infectious diseases, these vesicles can effectively deliver drugs to treat target disease, decrease the side effects and improve curative effect. With the development of PELN research, it is possible that PELN-based therapeutic options will multiply in the future, providing new avenues for disease prevention and treatment.

References

1. Bai C, Liu J, et al. Research status and challenges of plant-derived exosome-like nanoparticles. Biomed Pharmacother. 2024. 174, 116543.
2. Dad HA, Gu TW, et al. Plant Exosome-like Nanovesicles: Emerging Therapeutics and Drug Delivery Nanoplatforms. Mol Ther. 2021. 29(1), 13-31.

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