PNExo™ Exosome-Tomato(PNE-VT62)

Main Active Components in Tomato and Their Effects

• Lycopene: Potent antioxidant; reduces risk of chronic diseases such as cancer and cardiovascular ailments; neutralizes free radicals; prevents oxidative stress and inflammation.
• Beta-Carotene: Powerful antioxidant; supports eye health and immune function.
• Vitamin C: Boosts collagen production; aids in skin health and wound healing.
• Flavonoids: Exhibit anti-inflammatory and anti-cancer properties.

What Are Tomato-Derived Exosomes?

Exosomes are nanoscale extracellular vesicles secreted by cells, playing crucial roles in cell communication. Tomato-derived exosomes, obtained from the fruit and roots of the tomato plant, are garnering significant attention for their therapeutic and diagnostic potentials.
These vesicles are loaded with bioactive molecules such as proteins, lipids, and RNAs, reflecting the plant's metabolic state. Proteomic analyses of tomato-derived exosomes reveal proteins associated with inflammation, plant-microbe interactions, and cellular stress responses. Notably, they significantly inhibit the expression of inflammatory cytokine IL-1β, induced by lipopolysaccharides (LPS), showcasing their anti-inflammatory properties. Additionally, when loaded with curcumin via sonication, their anti-inflammatory activity is markedly enhanced.

The methodology focused on gathering and examining tiny Extracellular Vesicles (EVs) from tomato roots. (De Palma M, et al., 2020)

Applications of Tomato-Derived Exosomes

• Tomato-Derived Exosomes in Therapeutics

  Tomato-derived exosomes are emerging as promising candidates in the realm of regenerative medicine. Studies demonstrate their ability to improve the survival of adipose-derived stem cells without inducing toxicity, which is crucial for tissue engineering and cell therapy. These vesicles promote chondrocyte formation, suggesting their potential in cartilage regeneration and osteoarthritis treatment.
  In plant pathology, tomato root-derived extracellular vesicles exhibit significant inhibition of spore germination and germination tube development in plant pathogens. This points to their role in enhancing the plant immune system, which can be harnessed for developing eco-friendly plant protection strategies.

• Tomato-Derived Exosomes in Diagnostics

  The unique molecular cargo of tomato-derived exosomes holds potential for diagnostic applications. Their protein and RNA content can serve as biomarkers for various physiological and pathological states. For instance, their anti-inflammatory properties could be leveraged to develop diagnostic tools for inflammatory diseases. Moreover, the presence of proteins related to plant-microbe interactions suggests they could be used to monitor plant health and detect early signs of pathogen invasion.

• Skin Care Applications of Tomato-Derived Exosomes

  In the cosmetic industry, the bioactive compounds in tomato-derived exosomes offer innovative solutions for skin care. Their high antioxidant content helps combat oxidative stress, a major contributor to skin aging. The ability of these vesicles to boost collagen production and reduce inflammation makes them ideal for formulations aimed at anti-aging and skin repair.
  Furthermore, the incorporation of tomato-derived exosomes into skincare products can enhance the delivery and efficacy of active ingredients. Their natural origin and biocompatibility ensure they are well-tolerated by the skin, minimizing the risk of adverse reactions.

References

1. De Palma M, Ambrosone A, Leone A, et al. Plant roots release small extracellular vesicles with antifungal activity. Plants. 2020. 9(12): 1777.
2. Yıldırım M, Ünsal N, Kabataş B, et al. Effect of Solanum lycopersicum and citrus limon–derived exosome-like vesicles on chondrogenic differentiation of adipose-derived stem cells. Applied Biochemistry and Biotechnology. 2024. 196(1): 203-219.

Case study 1: De Palma M, 2020

Cell communication, both intra- and inter-species, is significantly facilitated by extracellular vesicles (EVs), with their environmental role in plants being an under-researched area. Recent studies have successfully isolated spherical EVs from the root exudates of hydroponically cultivated tomato plants, employing a method of sequential ultracentrifugation. These EVs, measured between 50 to 100 nm, were further characterized through biophysical examinations. A proteomic study identified a unique set of 179 proteins, many of which are implicated in plant-microbe interactions. Remarkably, these vesicles were found to substantially suppress the germination and early developmental stages of spores in plant pathogens such as Fusarium oxysporum, Botrytis cinerea, and Alternaria alternata. This discovery underscores the possible contribution of EVs to the plant's defense mechanisms.

Figure 1. Fungal spores' microscopic germination is influenced by increased concentrations of tomato root extracellular vesicles. Microscopic images (20×, Leica DMi8) captured at 24 hours post-inoculation, depicting the germination of Fusarium oxysporum, Botrytis cinerea, and Alternaria alternata spores in response to escalating tomato root-derived EV concentrations. The scale is indicated by a 50-micrometer bar.

Figure 2. Vesicles isolated from tomato roots manifest potent fungicidal properties, effectively combating a spectrum of plant pathogens. The mean germination rate of spores for Fusarium oxysporum, Botrytis cinerea, and Alternaria alternata was assessed after 48 hours post-inoculation with varying concentrations of tomato root extracellular vesicles (EVs). The control group's spores were cultivated in a medium supplemented with the EV resuspension buffer. The findings, which are an average of three separate experiments, demonstrate a statistically meaningful difference at the p < 0.05 level, as determined by one-way ANOVA followed by Tukey's post hoc analysis.

Case study 2: Mammadova R, 2023

Vesicles derived from botanical sources, specifically termed as Plant-derived Nanovesicles (PDNVs), have emerged as potential substitutes for extracellular vesicles that are typically derived from mammalian cells. These alternatives hold great promise for applications in therapeutics and the delivery of pharmaceuticals. A recent investigation has reported the isolation and fractionation of PDNVs derived from tomato fruit, which were separated into a dozen distinct fractions through the use of iodixanol density gradient ultracentrifugation (DGUC). These fractions, characterized by their particle dimensions, concentration levels, lipid profiles, and the spectrum of proteins they contain, have demonstrated notable anti-inflammatory properties. Notably, the fractions with intermediate and lower densities have been found to notably curtail the production of IL-1β cytokine mRNA triggered by lipopolysaccharides (LPS) in human monocytic cells of the THP-1 lineage. A proteomic examination has uncovered the presence of proteins that play a role in cellular functions and the modulation of inflammatory responses. Furthermore, the incorporation of curcumin into these PDNVs, achieved through direct loading and sonication techniques, has been shown to amplify their anti-inflammatory potency.

Figure 1. A diagrammatic depiction illustrates the fabrication techniques for tomato nanovesicles enriched with curcumin, encompassing three distinct approaches: the mechanical process of extrusion, the direct incorporation of curcumin followed by the application of a sucrose density gradient for ultracentrifugal separation, and the utilization of sonication to enhance the encapsulation efficiency.

Figure 2. Curcumin-loaded tomato vesicles' anti-inflammatory impact. (a) Conditions for pre-treatment and application. Curcumin served as a benchmark at varying concentrations. Fraction 8 from the Density Gradient Ultracentrifugation (DGUC Fr. 8) was either processed through extrusion (DGUC Fr. 8 extr., reference condition) or enriched via direct incubation followed by DGUC-based purification (DGUC Fr. 8 Inc.), as well as sonication (DGUC Fr. 8 son.). The anti-inflammatory potential was assessed in the THP-1 cell line by quantifying the secretion of inflammatory cytokines: (b) IL-1β; (c) IL-6. Across all experimental setups, a significant reduction in cytokine levels was observed when contrasted with the LPS-stimulated (10 ng/mL) scenario (statistical significance determined by ANOVA, complemented by Dunnett’s multiple comparison test; p ≤ 0.001).

References

1. De Palma M, Ambrosone A, Leone A, et al. Plant roots release small extracellular vesicles with antifungal activity. Plants. 2020. 9(12): 1777.
2. Mammadova R, Maggio S, Fiume I, et al. Protein biocargo and anti-inflammatory effect of tomato fruit-derived nanovesicles separated by density gradient ultracentrifugation and loaded with curcumin. Pharmaceutics. 2023. 15(2): 333.

• What are the main components of tomato exosomes?

  Tomato exosomes are rich in proteins, lipids, and RNAs. Proteomic analyses reveal a variety of proteins involved in inflammation regulation and plant defense mechanisms.

• What specific types of exosomes are derived from tomatoes?

  Tomato-derived exosomes primarily include those isolated from tomato fruit and roots, containing bioactive molecules tailored to plant-microbe interactions and therapeutic potentials.

• Can tomato exosomes be tailored for specific research?

  Yes, tomato exosomes can be engineered or loaded with specific payloads like curcumin to enhance anti-inflammatory properties or targeted delivery capabilities.

• What is the stability of tomato exosomes during storage and transportation?

  Tomato exosomes are stable under proper storage conditions (-80°C) and during transportation, maintaining their integrity and biological activity.

• Can tomato exosomes be customized for different research needs?

  Yes, we offer customization options for research needs, including loading with different bioactive molecules or adjusting exosome characteristics for specific applications.

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