PNExo™ Exosome-Green Tea(PNE-FLG70)

Benefits of Green Tea: Bioactive Components and Functions

Green tea (Camellia sinensis) is rich in bioactive compounds known for antioxidant, metabolic, and immune-modulating properties. Its main active constituents include:

• Catechins (Flavonoids): Key polyphenols like EGCG, EGC, ECG, and EC, with EGCG being the most potent. These compounds scavenge free radicals and chelate metal ions.
• EGCG: The dominant catechin with strong antioxidant activity, though its stability is pH-dependent and bioavailability is limited.
• Methylxanthines: Includes caffeine, theobromine, and theophylline, which stimulate metabolism and alertness by blocking adenosine receptors.
• L-Theanine: A unique amino acid that crosses the blood-brain barrier and regulates neurotransmitter balance for calm focus.
• Vitamins and Minerals: Provides vitamin C, E, B₂, β-carotene, and fluoride, supporting cellular health and immunity.
• Organic Acids: Compounds like gallic and oxalic acid add antioxidant and chelating functions.

What Are Green Tea-derived Exosomes?

Green tea-derived exosomes, also known as tea-derived exosome-like nanoparticles (TELNs), are nanoscale extracellular vesicles (EVs) obtained from Camellia sinensis. They are a subclass of plant-derived EVs and share many structural and functional features with mammalian exosomes, while possessing unique plant-specific characteristics.

• Structural Features: TELNs are spherical vesicles ranging from 30-250 nm in diameter, encapsulated by a phospholipid bilayer. Their surfaces carry membrane proteins such as tetraspanins and integrins, while internally they contain proteins, lipids, messenger RNAs, and microRNAs (miRNAs).
• Plant-specific miRNAs: TELNs uniquely carry plant-derived regulatory RNAs, such as miR-44 and miR-54, which have been reported to modulate mammalian gene expression via cross-kingdom interaction mechanisms. This feature sets them apart from exosomes of animal origin.
• Extraction Methods: These vesicles are typically isolated directly from tea leaf cells using established techniques such as ultracentrifugation, ultrafiltration, or precipitation-based methods.

Isolation and Characterization of TELNs. (a-d) TELNs were isolated from ground tea leaf juice by ultracentrifugation (UL) and gradient ultracentrifugation (GUL), with TELNs found at the 15/30% interface. (e) Representative TEM image of TELNs; white arrows indicate vesicle structures. Magnification: 50,000×; scale bar: 200 nm. (f) NTA analysis of TELNs showing particle size distribution. (Gong Q, et al., 2024)

Green Tea Exosome Advantages

Green tea-derived exosomes offer several distinctive advantages over synthetic nanocarriers and animal-derived vesicles, making them promising in biomedical and nutritional research:

• Natural Origin and Biocompatibility: Sourced from edible plants, TELNs are naturally safe with low immunogenicity. Their compatibility with oral use supports applications in functional food and supplement research.
• Inherent Bioactivity: TELNs retain green tea's active compounds such as polyphenols, amino acids, and plant microRNAs. These components contribute to antioxidant and anti-inflammatory effects without external modification.
• Structural Stability for Oral Delivery: The lipid bilayer of TELNs protects internal cargo from enzymatic degradation in the digestive tract. Their stability allows development into oral formulations like capsules or beverages.
• Regulatory Potential Across Species: Containing plant-specific microRNAs, TELNs have demonstrated the ability to influence mammalian gene expression, offering a natural pathway for interspecies molecular interaction studies.
• Efficient and Scalable Production: Green tea is widely cultivated, and TELNs can be extracted using established methods such as ultracentrifugation and ultrafiltration, supporting consistent and sustainable manufacturing.

Potential Applications of Tea-derived Exosomes

Intestinal Health and Anti-inflammatory Effects

Multiple studies have demonstrated that green tea-derived exosomes can support intestinal barrier integrity and reduce inflammation. Oral TELNs enhance tight junction protein expression and mitigate LPS-induced epithelial permeability, helping to prevent bacterial translocation across the gut mucosa. In stress-induced intestinal injury models, TELNs reduce epithelial damage markers such as serum endotoxin and restore mucosal integrity. Moreover, TELNs promote immune homeostasis by upregulating IL-22 and antimicrobial peptide Reg3g, while suppressing pro-inflammatory cytokines.

Cross-Kingdom Gene Regulation via Plant microRNAs

TELNs carry plant-derived microRNAs (e.g., miR-44, miR-54) that can be taken up by mammalian cells and modulate gene expression. For instance, miR-44 targets the TLR4/NF-κB signaling pathway, reducing inflammatory signaling in gut tissues, while miR-54 enhances mucin production, maintaining the protective mucus layer. This cross-kingdom communication mechanism represents a novel paradigm for dietary RNA-based modulation of host biology.

Natural Nanocarrier for Oral Drug Delivery

Thanks to their lipid bilayer structure, TELNs protect cargo from enzymatic degradation in the digestive tract, making them ideal for oral delivery. They have been successfully used to encapsulate chemotherapeutics, siRNAs, and piRNAs through methods like electroporation or co-incubation, enabling targeted delivery. Their stability in gastric conditions also allows formulation into enteric-coated capsules or functional beverages, expanding possibilities in therapeutic delivery systems.

Green tea-derived exosomes offer a unique combination of bioactivity, delivery potential, and safety. As research progresses, their integration with synthetic biology tools, such as surface peptide engineering or loading of functional RNA, may accelerate translational applications in inflammatory bowel diseases, cancer, and beyond.

References

1. Zu M, Xie D, Canup B S B, et al. 'Green'nanotherapeutics from tea leaves for orally targeted prevention and alleviation of colon diseases. Biomaterials. 2021, 279: 121178.
2. Gong Q, Zeng Z, Jiang T, et al. Anti-fibrotic effect of extracellular vesicles derived from tea leaves in hepatic stellate cells and liver fibrosis mice. Frontiers in Nutrition. 2022, 9: 1009139.
3. Chen Q, Zu M, Gong H, et al. Tea leaf-derived exosome-like nanotherapeutics retard breast tumor growth by pro-apoptosis and microbiota modulation. Journal of Nanobiotechnology. 2023, 21(1): 6.
4. Gong Q, Xiong F, Zheng Y, et al. Tea-derived exosome-like nanoparticles prevent irritable bowel syndrome induced by water avoidance stress in rat model. Journal of Gastroenterology and Hepatology. 2024, 39(12): 2690-2699.
5. Gong Q, Sun Y, Liu L, et al. Oral administration of tea-derived exosome-like nanoparticles protects epithelial and immune barrier of intestine from psychological stress. Heliyon. 2024, 10(17).
6. Liu Y, Qi H, Zong J, et al. Oral Piwi-Interacting RNA Delivery Mediated by Green Tea-Derived Exosome-Like Nanovesicles for the Treatment of Aortic Dissection. Advanced Healthcare Materials. 2024, 13(30): 2401466.
7. Luo T, Hou L, Cao Y, et al. Tea extracellular vesicle-derived microRNAs contribute to alleviate intestinal inflammation by reprogramming macrophages. Journal of Agricultural and Food Chemistry. 2025, 73(11): 6745-6757.
8. Lei X, Li H, Chen S, et al. Tea leaf exosome-like nanoparticles (TELNs) improve oleic acid-induced lipid metabolism by regulating miRNAs in HepG-2 cells. Bioresources and Bioprocessing. 2025, 12(1): 9.

Case Study 1: TLNTs Suppress Breast Tumor Growth via Apoptosis and Microbiota Modulation (Chen Q, 2023)

A study investigated the anti-tumor potential of tea leaf-derived exosome-like nanotherapeutics (TLNTs) against breast cancer. The TLNTs, with an average size of 166.9 nm and surface charge of -28.8 mV, were effectively internalized by over 80% of 4T1 breast cancer cells within 5 hours. In vitro, TLNTs induced a 2.5-fold increase in intracellular ROS, leading to mitochondrial dysfunction, G0/G1 and S phase arrest, and apoptosis rates of up to 67% after 8 hours.

In vivo experiments showed that orally administered TLNTs significantly reduced tumor volume by 2.2-fold at 3 mg/kg compared to controls, with no observed systemic toxicity. Transcriptomic analysis revealed upregulation of anti-tumor immune genes (e.g., NOS2, CCL4, CXCL9), while gut microbiota profiling indicated restored diversity and reduced abundance of pro-inflammatory bacteria like Oscillibacter and Desulfovibrio. Notably, the anti-tumor efficacy was markedly weakened when antibiotics were used, underscoring the critical role of microbiota in mediating the therapeutic effect.

This study highlights TLNTs as a promising, orally administrable, low-toxicity platform for modulating both tumor biology and the gut-tumor axis.

Figure 1. In Vitro Antitumor Activity of TLNTs in 4T1 and Other Tumor Cell Lines. (A) Cell viability assay showing TLNT cytotoxicity in multiple tumor cell lines after 24 and 48 h at increasing protein concentrations (0.5-64 µg/mL). (B) TLNT-induced apoptosis after 4 and 8 h incubation. (C) Confocal images of ROS production in 4T1 cells stained with DCFH-DA after TLNT treatment (scale bar: 50 μm). (D) Quantification of ROS fluorescence intensity. (E) Mitochondrial membrane potential assessment after TLNT exposure (scale bar: 50 μm). (F) Flow cytometry analysis of cell cycle distribution in 4T1 cells after 12 and 24 h TLNT treatment. (G) Western blot showing downregulation of cyclin A, B, and D after 48 h.

Figure 2. In Vivo Antitumor Efficacy of TLNTs in a Breast Cancer Mouse Model. (A) Body weight changes of tumor-bearing mice throughout the treatment period. (B) Tumor growth curves under different treatment conditions. (C) Final tumor weights measured at endpoint. (D) Representative tumor photographs from each treatment group. (E) Spleen weights of mice after treatment. (F) H&E and TUNEL staining of tumor sections showing histological alterations and apoptosis (scale bar: 100 μm).

Case Study 2: TELNs Protect Intestinal Barrier Under Stress Conditions (Gong Q, 2024)

A recent study demonstrated that tea-derived exosome-like nanoparticles (TELNs) can restore intestinal barrier integrity in rats subjected to psychological stress. Oral administration of TELNs (1 mg protein/kg) significantly reduced intestinal permeability, with FITC-dextran uptake and serum endotoxin levels decreased by over 50%.

TELNs upregulated tight junction proteins ZO-1 and occludin, preserving epithelial integrity both in vivo and in LPS-challenged Caco-2 cells, where they also improved transepithelial resistance. Immune barrier function was enhanced via increased IL-22 and Reg3g expression, reducing bacterial translocation across the mucosa.

Importantly, TELN-derived miR-44 and miR-54 boosted ZO-1 expression in a dose-dependent manner, suggesting a role in miRNA-mediated epithelial repair. These findings highlight TELNs as a promising plant-based approach for gut barrier protection under stress.

Figure 1. TELNs Protect Epithelial Barrier Integrity in Caco-2 Cells. (A) TEER values of Caco-2 monolayers measured from day 15 to day 21 post-seeding. (B) Relative TEER changes after treatment with different TELNs and LPS stimulation, normalized to initial TEER. (C, D) mRNA expression levels of tight junction markers ZO-1 and Occludin measured by RT-qPCR after TELNs and LPS treatment. Data normalized to control and β-ACTIN used as internal reference. (E) Immunofluorescence images of ZO-1 (green) and nuclei (DAPI, blue) showing junctional localization under different treatments. Scale bar = 50 μm. (F) Quantification of ZO-1 fluorescence intensity from (E) using ImageJ.

Figure 2. TELNs Reverse WAS-Induced Disruption of Tight Junction Structure. (A) Transmission electron microscopy images showing tight junction (solid arrows) and desmosome (dotted arrows) structures in different treatment groups. Scale bar = 500 nm; magnification: 30,000×. (B) Western blot analysis of tight junction proteins ZO-1 and Occludin in various groups. (C, D) RT-qPCR quantification of ZO-1 (C) and Occludin (D) mRNA levels across treatment groups.

Case Study 3: TELNs Modulate Lipid Metabolism in HepG-2 Cells (Lei X, 2025)

A recent study demonstrated that tea leaf-derived exosome-like nanoparticles (TELNs) can improve lipid metabolism in oleic acid-treated HepG-2 cells. TELNs (~249 nm, -20.6 mV) were efficiently internalized and showed no cytotoxicity up to 300 µg/mL.

Treatment with TELNs significantly reduced lipid accumulation, decreased TG, TC, and LDL-C levels, and increased HDL-C. Liver injury markers ALT and AST were also lowered. Mechanistic analysis revealed that TELNs suppressed miR-21-5p, miR-17-3p, and miR-107, leading to upregulation of their target genes PPAR-α, CYP7A1, and CPT1A, key regulators of fatty acid oxidation. These findings suggest TELNs hold promise as safe, plant-derived modulators of lipid metabolism through miRNA-mediated pathways.

Figure 1. TELNs Regulate Lipid Metabolism in HepG-2 Cells. (A) Oil Red O staining and grayscale analysis show that TELNs (300 μg/mL) reduce OA-induced lipid accumulation in HepG-2 cells. Red oil droplets were abundant in the OA group and significantly reduced in the TELNs group. (B-G) Dose-dependent effects of TELNs (100, 200, 300 μg/mL) on triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels.

Figure 2. TELNs Regulate Lipid Metabolism Genes via miRNA Interactions. (A) Predicted binding sites between miR-21-5p, miR-17-3p, and miR-107 and their lipid metabolism-related targets: PPAR-α, CYP7A1, and CPT1A. (B-D) TELNs treatment (300 μg/mL) significantly reduced expression of these miRNAs in HepG-2 cells compared to OA group. (E, F) Dual-luciferase reporter assays confirmed that the three miRNAs directly target the respective genes. Mutation of binding sites abolished the suppression effect.

References

1. Chen Q, Zu M, Gong H, et al. Tea leaf-derived exosome-like nanotherapeutics retard breast tumor growth by pro-apoptosis and microbiota modulation. Journal of Nanobiotechnology. 2023, 21(1): 6.
2. Gong Q, Sun Y, Liu L, et al. Oral administration of tea-derived exosome-like nanoparticles protects epithelial and immune barrier of intestine from psychological stress. Heliyon. 2024, 10(17).
3. Lei X, Li H, Chen S, et al. Tea leaf exosome-like nanoparticles (TELNs) improve oleic acid-induced lipid metabolism by regulating miRNAs in HepG-2 cells. Bioresources and Bioprocessing. 2025, 12(1): 9.

• What advantages do tea-derived exosomes have over synthetic delivery systems?

  Compared to synthetic nanoparticles, tea exosomes offer natural origin, lower toxicity, and inherent biological activity. They can protect encapsulated compounds from degradation, are well-tolerated when administered orally, and contain bioactive molecules such as polyphenols and miRNAs. Additionally, their production is plant-based and scalable, making them an eco-friendly alternative for nanodelivery research.

• Is the product quality-controlled for particle size, purity, and bioactivity?

  Yes. Each batch undergoes rigorous QC, including nanoparticle tracking analysis (NTA) for size and concentration, membrane integrity assays, and total protein/RNA content verification. This ensures consistent performance across experiments and compatibility with downstream applications such as miRNA profiling or drug loading.

• Are the green tea exosomes free from animal-derived components?

  Yes. This product is 100% plant-derived and free from any animal-origin materials. It is suitable for use in vegan-friendly research models and aligns with the requirements for plant-based or animal-free product development pipelines.

• Is bulk or customized packaging available for formulation-scale research?

  Yes. We offer customized packaging and bulk supply options upon request. Whether you need multiple milligram quantities for formulation screening or integration into pilot-scale R&D, our team can support tailored delivery formats with consistent batch quality.

• Is this product suitable for co-loading with small molecules or nucleic acids?

  Yes. These exosomes can be loaded with siRNA, miRNA mimics, or small molecules via electroporation, sonication, or incubation. We also provide exosome engineering services, including cargo loading and surface modification, to support custom research needs.

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