Development of Blueberry-Derived Extracellular Nanovesicles for Immunomodulatory Therapy

Abstract

Over the past decade, there has been a significant expansion in the development of plant-derived extracellular nanovesicles (EVs) as an effective drug delivery system for precision therapy. However, the lack of effective methods for the isolation and characterization of plant EVs hampers progress in the field. To solve a challenge related to systemic separation and characterization in the plant-derived EV field, herein, we report the development of a simple 3D inner filter-based method that allows the extraction of apoplastic fluid (AF) from blueberry, facilitating EV isolation as well as effective downstream applications. Class I chitinase (PR-3) was found in blueberry-derived EVs (BENVs). As Class I chitinase is expressed in a wide range of plants, it could serve as a universal marker for plant-derived EVs. Significantly, the BENVs exhibit not only higher drug loading capacity than that reported for other EVs but also possess the ability to modulate the release of the proinflammatory cytokine IL-8 and total glutathione in response to oxidative stress. Therefore, the BENV is a promising edible multifunctional nano-bio-platform for future immunomodulatory therapies.

The development of nanocarriers for natural products

“…3. Biomimetic nanocarriers from plant supramolecules: for instance, plant polysaccharides, proteins, and phospholipid bilayer vesicles can be meticulously extracted and exploited as nanocarriers, facilitating effective in vivo drug conveyance (Dad et al, 2021;Gong et al, 2022;Hadidi et al, 2023;Nguyen et al, 2023). This biomimetic self-assembly approach circumvents numerous drawbacks associated with synthetic carriers, such as mitigating toxicity and immunogenic responses and enhancing the safety and efficacy of drug transportation.…”

Emerging Trends and Translational Challenges in Drug and Vaccine Delivery

“…Another study focused on extracellular nanovesicles (EVs) that have great potential as drug delivery systems for precision therapy but are limited due to technical challenges to purify and characterize the EVs. To address this issue, Nguyen et al developed a 3D inner filter-based technique for the simple extraction of apoplastic fluid from blueberries, enabling EV purification [ 4 ]. The high drug loading capability and properties to modulate the release of proinflammatory cytokine IL-8 and total glutathione have enabled blueberry-derived EVs (BENVs) to be a promising edible multifunctional nano-bio-platform for future immunomodulatory therapies.…”

Stability of Blueberry Extracellular Vesicles and Their Gene Regulation Effects in Intestinal Caco-2 Cells

“…Mass spectrogram of 3-O-Methylgallic acid (C), Coumarin (D), Malvidin 3-O-β-D-galactoside (E), Isopeonidin 3-O-arabinoside (F), Malvidin 3-arabinosid (G), 5,6,7,3′,4′-Pentahydroxyisoflavone (H), Petunidin- glucoside (I), Luteolin (J), 6-O-Malonylgenistin (K). References [ 41 , 42 , 43 ] are cited in Supplementary Materials.…”