PNExo™ Exosome-Celery(PNE-VC02)

Benefits of Celery

• Reduces Inflammation: Contains antioxidants like flavonoids and polyphenols that help lower inflammation in the body.
• Lowers Blood Pressure: Phthalides in celery relax blood vessels and improve blood flow, helping to reduce hypertension.
• Nutrient-Rich: Rich in vitamins A, C, K, and potassium, essential for overall health and well-being.

What Are Celery-Derived Exosomes?

Celery-derived exosomes exhibit a round morphology with diameters predominantly around 140 nm, as observed through nanoparticle tracking analysis (NTA). These exosomes are well-dispersed, making them suitable for various biomedical applications.
Lipidomic analysis has identified several lipids within celery-derived exosomes, including diacylglycerol and phosphatidic acid, which are crucial for membrane fusion processes. Furthermore, gas chromatography-fatty acid methyl ester (GC-FAME) analysis has revealed the presence of anti-inflammatory fatty acids, indicating that these exosomes may play a role in modulating immune responses.
One remarkable property of celery-derived exosomes is their ability to be taken up by cells at a high rate without causing significant cytotoxicity. This makes them promising candidates for drug delivery and therapeutic applications.

Isolating and utilizing celery-derived exosomes for drug delivery. (Lu X, et al., 2023)

Applications of Celery-Derived Exosomes

• Celery-Derived Exosomes for Drug Delivery

  One of the most exciting applications of celery-derived exosomes is in the field of drug delivery. In both cellular and mouse subcutaneous tumor models of non-small cell lung cancer, treatment with these exosomes delivering anticancer drugs has shown promising results. The exosomes effectively reduced the proportion of Ki67+ cells (a marker of cell proliferation) and increased the proportion of Caspase3+ cells (a marker of apoptosis), demonstrating their potential in enhancing the therapeutic efficacy of anticancer drugs.

• Immunomodulation by Celery-Derived Exosomes

  Celery-derived exosomes have also demonstrated significant immunomodulatory effects. RT-PCR assays have shown that these exosomes can reduce the levels of pro-inflammatory markers such as IL-6 and IFNγ in activated T cells in a dose-dependent manner. This indicates their potential in treating inflammatory and autoimmune diseases.
  Furthermore, capillary immunoblotting assays have detected a reduction in the levels of phosphorylated T-cell activation link protein (p-LAT) and phosphorylated lymphocyte-specific protein tyrosine kinase (p-lck) proteins in activated T cells following treatment with celery-derived exosomes. This suggests that these exosomes can inhibit T-cell activation, making them promising candidates for immunotherapy.

• Anti-Inflammatory Properties of Celery-Derived Exosomes

  Flow cytometry analysis has further revealed that celery-derived exosomes can inhibit the activation of Jurkat cells (a model for T-cell leukemia) and down-regulate the proportion of CD4+CD25+ double-positive activated cells within the CD3+ cell population. Additionally, celery exosome treatment has been shown to decrease the levels of pro-inflammatory cytokines such as IL-8 and IL-12p70, which are typically elevated in response to PMA/ionomycin stimulation. This underscores their potential in reducing inflammation and treating inflammatory disorders.

• Celery-Derived Exosomes in Cancer Therapy

  The anti-inflammatory and immunomodulatory properties of celery-derived exosomes also extend to their potential use in cancer therapy. By modulating the immune response and enhancing the delivery of anticancer drugs, these exosomes can contribute to more effective cancer treatments. Their ability to reduce cell proliferation and induce apoptosis in cancer cells highlights their potential as a novel therapeutic approach in oncology.

References

1. Lu X, Han Q, Chen J, et al. Celery (Apium graveolens L.) exosome-like nanovesicles as a new-generation chemotherapy drug delivery platform against tumor proliferation. Journal of Agricultural and Food Chemistry. 2023. 71(22): 8413-8424.

Case study 1: Taşlı P N, 2022

Regulating the immune system has been a focus of various in vitro and in vivo studies. This study investigates the use of exosomes isolated from celery, a plant known for its anti-inflammatory properties, to suppress the inflammatory response of T lymphocytes. Celery-derived exosomes (C-Exo) were isolated using an aqueous two-phase method and analyzed for size, morphology, particle concentration, and lipid composition. T lymphocytes were stimulated with PMA/ionomycin and treated with different doses of C-Exo. Results showed that C-Exo suppressed T lymphocyte activity in a dose-dependent manner. This suggests that C-Exo could be a therapeutic agent for immune-related disorders.

Figure 1. Effect of celery-derived exosomes on Jurkat cells. Utilizing flow cytometric techniques, it was observed that the introduction of these exosomes resulted in a suppression of Jurkat cell activation. Furthermore, there was a notable decrease in the frequency of cells co-expressing CD4 and CD25 markers within the CD3+ cell subset.

Case study 2: Lu X, 2023

Extracellular vesicles (EVs) have demonstrated significant potential in drug delivery, yet their clinical use is limited by high production costs and complex purification processes. Plant-derived exosome-like nanovesicles offer a promising alternative, with celery exosome-like nanovesicles (CELNs) showing particularly high cellular uptake efficiency. This makes CELNs advantageous as drug carriers. In mouse models, CELNs exhibited lower toxicity and better tolerance as biotherapeutics. When doxorubicin (DOX) was encapsulated into CELNs to create engineered CELNs (CELNs-DOX), they proved more effective in tumor treatment than traditional synthetic carriers like liposomes, both in vitro and in vivo. This study highlights CELNs as a promising new-generation drug delivery carrier.

References

1. Taşlı P N. Usage of celery root exosome as an immune suppressant; Lipidomic characterization of apium graveolens originated exosomes and its suppressive effect on PMA/ionomycin mediated CD4+ T lymphocyte activation. Journal of Food Biochemistry. 2022. 46(12): e14393.
2. Lu X, Han Q, Chen J, et al. Celery (Apium graveolens L.) exosome-like nanovesicles as a new-generation chemotherapy drug delivery platform against tumor proliferation. Journal of Agricultural and Food Chemistry. 2023. 71(22): 8413-8424.

• What specific bioactive molecules are present in celery-derived exosomes?

  Celery-derived exosomes contain a variety of bioactive molecules, including diacylglycerol and phosphatidic acid, which are crucial for membrane fusion processes. They also carry fatty acids with anti-inflammatory properties, contributing to their ability to modulate immune responses and reduce inflammation.

• Can celery-derived exosomes be scaled up for mass production, and what measures are in place to maintain their stability during storage and transportation?

  Yes, our celery-derived exosomes can be scaled up for mass production. We have developed optimized protocols to ensure their stability during storage and transportation, including lyophilization techniques and the use of cryoprotectants to maintain their bioactivity.

• How do celery-derived exosomes compare to other plant-derived exosomes or synthetic nanocarriers in terms of delivery efficiency?

  Compared to other plant-derived exosomes and synthetic nanocarriers, celery-derived exosomes exhibit higher cellular uptake efficiency and lower toxicity. Their natural composition and ability to carry a diverse range of bioactive molecules give them an edge in terms of delivery efficiency.

• Can celery-derived exosomes be customized to carry specific therapeutic agents?

  Yes, celery-derived exosomes can be customized to carry specific therapeutic agents. We offer various customization options according to your research requirements.

• How do you ensure the batch-to-batch consistency of celery-derived exosomes during production?

  We ensure batch-to-batch consistency through rigorous quality control measures at every stage of production. This includes standardized isolation procedures, detailed characterization of each batch for size, morphology, and bioactive content, and adherence to Good Manufacturing Practices (GMP).

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