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Exosomes, a category of extracellular vesicle (EV), are phospholipid bilayer structures ranging from 30 to 150 nm, produced by various organisms through the endosomal pathway. Recent studies have established the utilization of exosomes as nanocarriers for drug distribution across various therapeutic areas including cancer, acute liver injury, neuroprotection, oxidative stress, inflammation, etc. The importance of plant-derived exosomes and exosome vesicles derived from mammalian cells or milk, loaded with potent plant bioactives for various therapeutic indications are discussed along with insights into future perspectives. Moreover, this review provides a detailed understanding of exosome biogenesis, their composition, classification, stability of different types of exosomes, and different routes of administration along with the standard techniques used for isolating, purifying, and characterizing exosomes. Plain Language Summary Exosomes are tiny, spherical structures made of two layers of lipids, measuring between 30 and 150 nm in diameter. They are flexible, less harmful to the immune system, can cross barriers in the body, and also can be used as vehicles to carry drugs. Various methods are used to obtain, separate, and purify the exosomes based on their size, shape, density, and specific markers. Exosomes obtained from plants can treat various diseases as they are less toxic, have high permeability, and are environmentally safe. The chemical compounds obtained from plants can be loaded into the exosomes obtained from sources like milk, or human cells both healthy and diseased, having the ability to treat cancer, inflammation, liver diseases, etc. GRAPHICAL ABSTRACT Article highlights Introduction to exosomes Exosomes are small vesicles released by most eukaryotic cells, that facilitate intercellular communication and possess an extended half-life, allowing them to traverse extended distances within the body under both normal and disease conditions. Advantages of exosomes The exceptional drug-delivery potential of exosomes, originating from their less immunogenic, non-cytotoxic, and non-mutagenic ability, surpasses that of liposomes. In advanced medicine, exosomes are investigated as a promising cell-free therapy due to their targeted effects on cells, reduced safety issues, and low manufacturing costs in comparison to cell-based therapies. Challenges with exosomes Human cell-derived exosomes have scalability and scalability challenges associated with the low yield. To address this exosome-derived plants have emerged as a promising alternative. Ethical concerns Researchers must thoroughly evaluate the potential risks associated with exosome-based therapies, including immunogenicity, off-target effects, and long-term complications. Patients should be fully informed about the nature of exosome therapy, including its potential benefits, risks, and uncertainties. In-depth investigation of the animal-derived, and plant-derived exosomes is required before using them for therapeutic interventions. Advantages of plant-derived exosomes Plant-derived exosomes owing to their small size are considered to be environmentally safe, less toxic, and have high permeability; biological functions and pharmacological properties of plant-derived exosomes closely resemble those of their parent plants and often surpass those of isolated plant compounds. Isolation & purification methods The selection of different isolation and purification methods such as ultracentrifugation, size-based separation, polymer-based methods, affinity-based separation, and microfluidic systems are to be taken care of as they can influence the purity and the physiological characteristics of the exosomes. Future perspectives The plant-derived exosomes with their superior advantages of higher yield, widely available, prolonged half-life, and better stability in biological fluids show future potential for treatment strategy and therapeutic intervention. [ABSTRACT FROM AUTHOR]

Plant‐derived exosomes (PEs) possess an array of therapeutic properties, including antitumor, antiviral, and anti‐inflammatory capabilities. They are also implicated in defensive responses to pathogenic attacks. Spinal cord injuries (SCIs) regeneration represents a global medical challenge, with appropriate research concentration on three pivotal domains: neural regeneration promotion, inflammation inhibition, and innovation and application of regenerative scaffolds. Unfortunately, the utilization of PE in SCI therapy remains unexplored. Herein, we isolated PE from the traditional Chinese medicinal herb, Lycium barbarum L. and discovered their inflammatory inhibition and neuronal differentiation promotion capabilities. Compared with exosomes derived from ectomesenchymal stem cells (EMSCs), PE demonstrated a substantial enhancement in neural differentiation. We encapsulated isoliquiritigenin (ISL)‐loaded plant‐derived exosomes (ISL@PE) from L. barbarum L. within a 3D‐printed bionic scaffold. The intricate construct modulated the inflammatory response following SCI, facilitating the restoration of damaged axons and culminating in ameliorated neurological function. This pioneering investigation proposes a novel potential route for insoluble drug delivery via plant exosomes, as well as SCI repair. The institutional animal care and use committee number is UJS‐IACUC‐2020121602. [ABSTRACT FROM AUTHOR]

Extracellular vesicle (EV) research has expanded substantially over the years. EVs have been identified in all living organisms and are produced and released as a means of intercellular communication or as a defense mechanism. Recently, nano-scaled vesicles were successfully isolated from edible plant sources. Plant-derived EVs, referred to here as phytosomes, are of a size reported to range between 30 nm and 120 nm in diameter, similar to small mammalian extracellular vesicles, and carry various bioactive molecules such as mRNA, proteins, miRNA and lipids. Due to the availability of many plants, phytosomes can be easily isolated on a large scale. The methods developed for EV isolation from mammalian cells have been successfully applied for isolation and purification of phytosomes. The therapeutic effects of phytosomes on different disease models, such as inflammation and autoimmune disease, have been reported, and a handful of studies have suggested their therapeutic effects on cancer diseases. Overall, the research on phytosomes is still in its infancy and requires more exploration. This review will narrate the anti-cancer activity and characteristics of phytosomes derived from edible plants as well as describe studies which have utilized phytosomes as drug delivery vehicles for cancer with the ultimate objective of significantly reducing the adverse effects associated with conventional therapeutic approaches. [ABSTRACT FROM AUTHOR]

Plant-derived exosomes (PDEs) are receiving much attention as a natural source of antioxidants. Previous research has shown that PDEs contain a series of bioactives and that their content varies depending on the fruit or vegetable source. It has also been shown that fruits and vegetables derived from organic agriculture produce more exosomes, are safer, free of toxic substances, and contain more bioactives. The aim of this study was to investigate the ability of orally administered mixes of PDE (Exocomplex®) to restore the physiological conditions of mice treated for two weeks with hydrogen peroxide (H2O2), compared with mice left untreated after the period of H2O2 administration and mice that received only water during the experimental period. The results showed that Exocomplex® had a high antioxidant capacity and contained a series of bioactives, including Catalase, Glutathione (GSH), Superoxide Dismutase (SOD), Ascorbic Acid, Melatonin, Phenolic compounds, and ATP. The oral administration of Exocomplex® to the H2O2-treated mice re-established redox balance with reduced serum levels of both reactive oxygen species (ROS) and malondialdehyde (MDA), but also a general recovery of the homeostatic condition at the organ level, supporting the future use of PDE for health care. [ABSTRACT FROM AUTHOR]

Plant-derived exosomes (PLDEs) are small extracellular vesicles that encapsulate proteins, nucleic acids and lipids, and they are usually involved in intercellular communication and molecular transport in plants. PLDEs are widely used in the therapy of diseases due to their abundance and easy availability. The diverse roles of PLDEs, which include transportation of drugs, acting as biomarkers for diagnosis of diseases and their roles in different therapies, suggest that there is a need to fully understand all the mechanisms involved in order to provide the optimum conditions for their therapeutic use. This review summarizes the biogenesis, components and functions of PLDEs and focuses on their use as therapeutic agents in the treatment of inflammatory diseases. It also explores new ideas for novel approaches in which PLDEs could potentially help patients with inflammatory diseases in the future. [ABSTRACT FROM AUTHOR]

Plant-derived exosomes (PDEs), are nanoscale vesicles secreted by multivesicular bodies, play pivotal roles in critical biological processes, including gene regulation, cell communication, and immune defense against pathogens. Recognized for their potential health-promoting properties, PDEs are emerging as innovative components in functional nutrition, poised to enhance dietary health benefits. To describe the efficacy of PDEs in nanoform and their application as precision therapy in many disorders. The design of this review was carried out in PICO format using randomized clinical trials and research articles based on in vivo and in vitro studies. All the relevant clinical and research studies conducted on plant-derived nanovesicle application and efficacy were included, as retrieved from PubMed and Cochrane, after using specific search terms. This review was performed to determine PDEs' efficacy as nanomedicine and precision therapy. Sub-group analysis and primary data were included to determine the relationship with PDEs. PDEs are extracted from plant materials using sophisticated techniques like precipitation, size exclusion, immunoaffinity capture, and ultracentrifugation, encapsulating vital molecules such as lipids, proteins, and predominantly microRNAs. Although their nutritional impact may be minimal in small quantities, the broader application of PDEs in biomedicine, particularly as vehicles for drug delivery, underscores their significance. They offer a promising strategy to improve the bioavailability and efficacy of therapeutic agents carrying nano-bioactive substances that exhibit anti-inflammatory, antioxidant, cardioprotective, and anti-cancer activities. PDEs enhance the therapeutic potency of plant-derived phytochemicals, supporting their use in disease prevention and therapy. This comprehensive review explores the multifaceted aspects of PDEs, including their isolation methods, biochemical composition, health implications, and potential to advance medical and nutritional interventions. [Display omitted] [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic recurrent intestinal disease and includes Crohn's disease (CD) and ulcerative colitis (UC). Due to the complex etiology of colitis, the current treatments of IBD are quite limited and are mainly concentrated on the remission of the disease. In addition, the side effects of conventional drugs on the body cannot be ignored. IBD also has a certain relationship with colitis-associated cancer (CAC), and inflammatory cells can produce a large number of tumor-promoting cytokines to promote tumor progression. In recent years, exosomes from plants have been found to have the ability to load drugs to target the intestine and have great potential for the treatment of intestinal diseases. This plant-derived exosome-targeting delivery system can load chemical or nucleic acid drugs and deliver them to intestinal inflammatory sites stably and efficiently. This review summarizes the pathophysiological characteristics of IBD and CAC as well as the application and prospect of plant exosomes in the treatment of IBD and CAC. [ABSTRACT FROM AUTHOR]

Plant-derived exosomes (PDEs) are receiving much attention as a natural source of antioxidants. Previous research has shown that PDEs contain a series of bioactives and that their content varies depending on the fruit or vegetable source. It has also been shown that fruits and vegetables derived from organic agriculture produce more exosomes, are safer, free of toxic substances, and contain more bioactives. The aim of this study was to investigate the ability of orally administered mixes of PDE (Exocomplex®) to restore the physiological conditions of mice treated for two weeks with hydrogen peroxide (H2O2), compared with mice left untreated after the period of H2O2 administration and mice that received only water during the experimental period. The results showed that Exocomplex® had a high antioxidant capacity and contained a series of bioactives, including Catalase, Glutathione (GSH), Superoxide Dismutase (SOD), Ascorbic Acid, Melatonin, Phenolic compounds, and ATP. The oral administration of Exocomplex® to the H2O2-treated mice re-established redox balance with reduced serum levels of both reactive oxygen species (ROS) and malondialdehyde (MDA), but also a general recovery of the homeostatic condition at the organ level, supporting the future use of PDE for health care.

Plant-derived exosomes (PLDEs) are small extracellular vesicles that encapsulate proteins, nucleic acids and lipids, and they are usually involved in intercellular communication and molecular transport in plants. PLDEs are widely used in the therapy of diseases due to their abundance and easy availability. The diverse roles of PLDEs, which include transportation of drugs, acting as biomarkers for diagnosis of diseases and their roles in different therapies, suggest that there is a need to fully understand all the mechanisms involved in order to provide the optimum conditions for their therapeutic use. This review summarizes the biogenesis, components and functions of PLDEs and focuses on their use as therapeutic agents in the treatment of inflammatory diseases. It also explores new ideas for novel approaches in which PLDEs could potentially help patients with inflammatory diseases in the future.

Differentiation of bone marrow derived mesenchymal stem cells (BMSCs) into functional neural cells has been widely investigated for treating neural diseases. However, the limited neural differentiation of BMSCs remains a big challenge to overcome. Herein, for the first time, ginseng-derived exosomes (G-Exos) were demonstrated to have excellent efficiency in stimulating the neural differentiation of BMSCs by transferring the incorporated miRNAs to BMSCs efficiently. In vivo, a photo-cross-linkable hydrogel with chemokine and G-Exos loaded shows strong efficacy in recruiting and directing the neural differentiation of BMSCs in the program. G-Exos were demonstrated to be promising nanoplatforms in transferring plant-derived miRNAs to mammalian stem cells for neural differentiation both in vitro and in vivo, possessing great potential in neural regenerative medicine.