PNExo™ Exosome-Strawberry

Benefits of Strawberry

Strawberry (Fragaria × ananassa) is a rich source of diverse phytochemicals known for their antioxidant, anti-inflammatory, neuroprotective, and metabolic regulatory activities, as demonstrated in various in vitro and in vivo models. These compounds function through multiple cellular pathways, modulating oxidative stress, inflammatory responses, vascular health, and microbial growth. Below is a summary of the major bioactive constituents identified in strawberries and their associated biological effects:

• Anthocyanins (e.g. Pelargonidin-3-O-glucoside, Cyanidin-3-O-glucoside): Representing the dominant polyphenols in strawberries, pelargonidin-3-O-glucoside accounts for over 90% of total anthocyanins. These pigments exhibit potent antioxidant properties by neutralizing free radicals and inhibiting lipid peroxidation. Studies have also linked them to anti-inflammatory actions, including the suppression of CD40-mediated signaling, neuroprotective effects in models of neurodegenerative disease, and liver-protective roles against galactose-induced oxidative stress.
• Flavanols (e.g. (+)-Catechin, (-)-Epicatechin): These compounds enhance endothelial function by promoting nitric oxide production and reducing cardiovascular risk factors such as acute myocardial infarction. Flavanols also synergize with anthocyanins to boost total antioxidant capacity (TAC), contributing to cellular redox balance.
• Phenolic Acids (e.g. Ellagic acid, Gallic acid, 5-Caffeoylquinic acid): Known for their anticancer and antimicrobial properties, ellagic acid has been shown to induce apoptosis in cancer cells and suppress proliferation, particularly in colon and breast cancer models. These acids also inhibit the growth of Helicobacter pylori, a key factor in gastritis, and modulate glucose metabolism by improving insulin sensitivity.
• Vitamin C (Ascorbic Acid): Strawberries are a superior dietary source of vitamin C, with levels up to 11 times higher than apples, especially in organically cultivated varieties. Vitamin C accounts for approximately 24% of the fruit’s total antioxidant activity and plays a critical role in collagen synthesis, immune defense, and the prevention of LDL oxidation, particularly in synergy with polyphenols.
• Folate: A crucial B-vitamin present in strawberries, folate supports DNA synthesis and repair, and its intake is associated with reduced risk of neural tube defects, ischemic events, and certain cancers.

What Are Strawberry-Derived Exosomes?

Strawberry exosome-like nanovesicles (SELNs) are naturally occurring nanosized vesicles (typically 30 - 191 nm) isolated from Fragaria × ananassa fruit. Morphologically, they display the characteristic cup- or disc-like shape observed in mammalian extracellular vesicles. These vesicles are produced by plant cells through endocytosis, multivesicular body formation, and exocytosis, and they contain a lipid bilayer that encapsulates a range of functional biomolecules, including proteins, small RNAs (such as miRNAs), lipids, and antioxidants like vitamin C.

The growing interest in strawberry-derived exosomes for scientific research is driven by several distinct advantages:

• Natural Origin: Extracted directly from edible fruit tissue, SELNs offer a biogenic platform for investigating intercellular communication and molecular transport.
• High Biocompatibility: Strawberry-derived vesicles are efficiently internalized by human cells, such as mesenchymal stem cells, without inducing cytotoxicity, suggesting broad compatibility with mammalian systems.
• Antioxidant-Enriched Cargo: These vesicles are naturally enriched in antioxidant compounds, particularly vitamin C and phenolics, which may contribute to their protective roles in oxidative stress models.
• Drug Delivery Potential: The lipid bilayer structure enhances cargo stability, supporting the potential of SELNs as plant-derived nanocarriers for small molecules or experimental therapeutics.

Isolation and characterization of Fragaria-derived exosome-like nanovesicles (EPDENs). (a) Schematic diagram illustrating the protocol used to extract and purify EPDENs from Fragaria x ananassa. (b - d) Transmission electron microscopy (TEM) images of exosome-like nanovesicles isolated from (b) Fragaria x ananassa, (c) Citrus limon L., and (d) adipose-derived mesenchymal stem cells (ADMSCs). Scale bar: 100 nm. (Perut F, et al., 2021)

Potential Applications of Strawberry Exosomes

Cellular Protection Against Oxidative Stress

Pretreatment of human adipose-derived mesenchymal stem cells (ADMSCs) with strawberry exosome-like nanovesicles (SELNs) has been shown to enhance cellular resistance to oxidative damage induced by hydrogen peroxide (H₂O₂). This protective effect occurs in a dose-dependent manner and is likely attributed to the high content of vitamin C encapsulated within the nanovesicles, which plays a central role in neutralizing reactive oxygen species (ROS) and preserving redox homeostasis.

Biocompatibility and Cellular Uptake

SELNs exhibit efficient uptake by human cells without inducing cytotoxicity, even at higher concentrations. This high level of biocompatibility highlights their promise as naturally derived nanoscale agents for investigating cell-nanoparticle interactions and biological delivery systems in vitro.

Antioxidant Cargo Retention and Stability

Encapsulation of vitamin C within the lipid bilayer structure of SELNs may offer improved stability over free-form antioxidants. Studies comparing SELNs with citrus-derived vesicles indicate that strawberry nanovesicles possess higher ascorbic acid content, potentially enhancing their antioxidative efficacy in cellular models.

Presence of Small RNAs and miRNA

Molecular profiling has confirmed the presence of small RNAs and specific microRNAs, such as miR166g, within strawberry-derived SELNs. These RNA species are selectively enriched compared to whole fruit juice and are thought to play roles in cell signaling and stress response, though their activity in cross-species systems remains an area of ongoing investigation.

Overall, SELNs represent a natural, stable, and bioactive nanovesicle system with emerging applications in oxidative stress research, antioxidant delivery, and plant-to-mammal molecular interaction studies. Continued research is needed to further characterize their mechanisms of action and potential broader utility in biotechnology and cellular biology.

References

1. Perut F, Roncuzzi L, Avnet S, et al. Strawberry-derived exosome-like nanoparticles prevent oxidative stress in human mesenchymal stromal cells. Biomolecules. 2021, 11(1): 87.
2. Danh J, Canup B, Najjar R, et al. Characterization and uptake of strawberry-derived exosome-like nanovesicles by human aortic endothelial cells. Current Developments in Nutrition. 2021, 5: 310.
3. Stanly C, Kim H, Antonucci G, et al. Crosstalk between the immune system and plant-derived nanovesicles: a study of allergen transporting. Frontiers in Bioengineering and Biotechnology. 2021, 9: 760730.
4. Chen Y X, Cai Q. Plant exosome-like nanovesicles and their role in the innovative delivery of RNA therapeutics. Biomedicines. 2023, 11(7): 1806.
5. Mu N, Li J, Zeng L, et al. Plant-derived exosome-like nanovesicles: current progress and prospects. International Journal of Nanomedicine. 2023: 4987 - 5009.