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Keywords = plant-derived exosomes

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17 pages, 2759 KiB  
Article
Hemp Seed-Derived Exosomes Protect Against Dihydrotestosterone-Induced Chicken Feather Growth Inhibition
by Hwapyung Kim, Gwangpyung Kim, Namsoo Peter Kim and Boyong Kim
Pharmaceuticals 2025, 18(8), 1192; https://doi.org/10.3390/ph18081192 - 13 Aug 2025
Viewed by 130
Abstract
Background/Objectives: Androgenetic alopecia suppresses hair follicle growth. This occurs via dihydrotestosterone (DHT), which inhibits key molecular pathways such as Wnt/β-catenin and Sonic Hedgehog (SHH) signaling. Exosomes derived from plant callus cultures are promising biomaterials for targeted delivery and regenerative medicine. This study aimed [...] Read more.
Background/Objectives: Androgenetic alopecia suppresses hair follicle growth. This occurs via dihydrotestosterone (DHT), which inhibits key molecular pathways such as Wnt/β-catenin and Sonic Hedgehog (SHH) signaling. Exosomes derived from plant callus cultures are promising biomaterials for targeted delivery and regenerative medicine. This study aimed to investigate the protective effects of hemp seed callus-derived exosomes (E40) against DHT-induced inhibition of feather follicle development in a chicken embryo model. Methods: E40 exosomes were isolated and purified from the calli of germinated hemp seeds. A DHT-induced feather loss model was established by injecting chicken embryos on embryonic day 7 (E7) with DHT (50 ng/mL), with or without co-administration of E40 (40 µg/mL). On embryonic day 12 (E12), feather length, density, and expression of molecular markers were analyzed. The methods included FISH, Western blotting, and quantitative analysis of PTCH1, AR, SHH, SMO, GLI1, Wnt, β-catenin, BMP4, and Noggin. Results: DHT treatment significantly reduced feather length and density. It also downregulated SHH and Wnt/β-catenin markers, upregulating BMP4 and androgen receptor expression. Co-treatment with E40 restored feather length and density to levels comparable to controls and significantly recovered the expression of SHH, SMO, GLI1, Wnt, and β-catenin. E40 also suppressed DHT-induced BMP4 upregulation by approximately 30% and reduced androgen receptor expression. Conclusions: These results suggest that hemp seed-derived exosomes (E40) effectively mitigate DHT-induced feather follicle inhibition by modulating critical signaling pathways and immune-related markers, supporting their potential application as a nanocarrier-based therapeutic strategy for alopecia management. Full article
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27 pages, 15398 KiB  
Article
Epimedium-Derived Exosome-Loaded GelMA Hydrogel Enhances MC3T3-E1 Osteogenesis via PI3K/Akt Pathway
by Weijian Hu, Xin Xie and Jiabin Xu
Cells 2025, 14(15), 1214; https://doi.org/10.3390/cells14151214 - 7 Aug 2025
Viewed by 498
Abstract
Healing large bone defects remains challenging. Gelatin scaffolds are biocompatible and biodegradable, but lack osteoinductive activity. Plant-derived exosomes carry miRNAs, growth factors, and proteins that modulate osteogenesis, but free exosomes suffer from poor stability, limited targeting, and low bioavailability in vivo. We developed [...] Read more.
Healing large bone defects remains challenging. Gelatin scaffolds are biocompatible and biodegradable, but lack osteoinductive activity. Plant-derived exosomes carry miRNAs, growth factors, and proteins that modulate osteogenesis, but free exosomes suffer from poor stability, limited targeting, and low bioavailability in vivo. We developed a 3D GelMA hydrogel loaded with Epimedium-derived exosomes (“GelMA@Exo”) to improve exosome retention, stability, and sustained release. Its effects on MC3T3-E1 preosteoblasts—including proliferation, osteogenic differentiation, migration, and senescence—were evaluated via in vitro assays. Angiogenic potential was assessed using HUVECs. Underlying mechanisms were examined at transcriptomic and protein levels to elucidate GelMA@Exo’s therapeutic osteogenesis actions. GelMA@Exo exhibited sustained exosome release, enhancing exosome retention and cellular uptake. In vitro, GelMA@Exo markedly boosted MC3T3-E1 proliferation, migration, and mineralized nodule formation, while reducing senescence markers and promoting angiogenesis in HUVECs. Mechanistically, GelMA@Exo upregulated key osteogenic markers (RUNX2, TGF-β1, Osterix, COL1A1, ALPL) and activated the PI3K/Akt pathway. Transcriptomic data confirmed global upregulation of osteogenesis-related genes and bone-regeneration pathways. This study presents a GelMA hydrogel functionalized with plant-derived exosomes, which synergistically provides osteoinductive stimuli and structural support. The GelMA@Exo platform offers a versatile strategy for localized delivery of natural bioactive molecules and a promising approach for bone tissue engineering. Our findings provide strong experimental evidence for the translational potential of plant-derived exosomes in regenerative medicine. Full article
(This article belongs to the Section Cell Proliferation and Division)
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30 pages, 7811 KiB  
Article
Preparation and Characterization of Cyperus-Derived Exosomes Loaded with Selenium Nanoparticles for Selenium Delivery Based on Exosome Protein Quantitation
by Dexiu Zhao, Xiaojun Yang, Abulimiti Kelimu, Bin Wu, Weicheng Hu, Hongbo Fan, Lei Jing, Dongmei Yang and Xinhong Huang
Foods 2025, 14(15), 2724; https://doi.org/10.3390/foods14152724 - 4 Aug 2025
Viewed by 446
Abstract
Appropriate carriers or templates are crucial for maintaining the stability, biological activity, and bioavailability of selenium nanoparticles (SeNPs). Selecting suitable templates remains challenging for fully utilizing SeNPs functionalities and developing applicable products. Exosome-like nanoparticles (ELNs) have gained importance in drug delivery systems, yet [...] Read more.
Appropriate carriers or templates are crucial for maintaining the stability, biological activity, and bioavailability of selenium nanoparticles (SeNPs). Selecting suitable templates remains challenging for fully utilizing SeNPs functionalities and developing applicable products. Exosome-like nanoparticles (ELNs) have gained importance in drug delivery systems, yet research on selenium products prepared using exosomes remains limited. To address this gap, we utilized Cyperus bean ELNs to deliver SeNPs, investigated three preparation methods for SeNPs-ELNs, identified the optimal approach, and performed characterization studies. Notably, all three methods successfully loaded SeNPs. Ultrasonic cell fragmentation is the optimal approach, achieving significant increases in selenium loading (5.59 ± 0.167 ng/μg), enlargement of particle size (431.17 ± 10.78 nm), and reduced absolute zeta potential (−4.1 ± 0.43 mV). Moreover, both exosome formulations demonstrated enhanced stability against aggregation during storage at 4 °C, while their stability varied with pH conditions. In vitro digestibility tests showed greater stability of SeNP-ELNs in digestive fluids compared to ELNs alone. Additionally, neither ELNs nor SeNP-ELNs exhibited cytotoxicity toward LO2 cells, and the relative erythrocyte hemolysis remained below 5% at protein concentrations of 2.5, 7.5, 15, 30, and 60 μg/mL. Overall, ultrasonic cell fragmentation effectively loaded plant-derived exosomes with nano-selenium at high capacity, presenting new opportunities for their use as functional components in food and pharmaceutical applications. Full article
(This article belongs to the Section Food Nutrition)
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26 pages, 9475 KiB  
Article
Microalgae-Derived Vesicles: Natural Nanocarriers of Exogenous and Endogenous Proteins
by Luiza Garaeva, Eugene Tolstyko, Elena Putevich, Yury Kil, Anastasiia Spitsyna, Svetlana Emelianova, Anastasia Solianik, Eugeny Yastremsky, Yuri Garmay, Elena Komarova, Elena Varfolomeeva, Anton Ershov, Irina Sizova, Evgeny Pichkur, Ilya A. Vinnikov, Varvara Kvanchiani, Alina Kilasoniya Marfina, Andrey L. Konevega and Tatiana Shtam
Plants 2025, 14(15), 2354; https://doi.org/10.3390/plants14152354 - 31 Jul 2025
Viewed by 431
Abstract
Extracellular vesicles (EVs), nanoscale membrane-enclosed particles, are natural carriers of proteins and nucleic acids. Microalgae are widely used as a source of bioactive substances in the food and cosmetic industries and definitely have a potential to be used as the producers of EVs [...] Read more.
Extracellular vesicles (EVs), nanoscale membrane-enclosed particles, are natural carriers of proteins and nucleic acids. Microalgae are widely used as a source of bioactive substances in the food and cosmetic industries and definitely have a potential to be used as the producers of EVs for biomedical applications. In this study, the extracellular vesicles isolated from the culture medium of two unicellular microalgae, Chlamydomonas reinhardtii (Chlamy-EVs) and Parachlorella kessleri (Chlore-EVs), were characterized by atomic force microscopy (AFM), cryo-electronic microscopy (cryo-EM), and nanoparticle tracking analysis (NTA). The biocompatibility with human cells in vitro (HEK-293T, DF-2 and A172) and biodistribution in mouse organs and tissues in vivo were tested for both microalgal EVs. An exogenous therapeutic protein, human heat shock protein 70 (HSP70), was successfully loaded to Chlamy- and Chlore-EVs, and its efficient delivery to human glioma and colon carcinoma cell lines has been confirmed. Additionally, in order to search for potential therapeutic biomolecules within the EVs, their proteomes have been characterized. A total of 105 proteins were identified for Chlamy-EVs and 33 for Chlore-EVs. The presence of superoxide dismutase and catalase in the Chlamy-EV constituents allows for considering them as antioxidant agents. The effective delivery of exogenous cargo to human cells and the possibility of the particle yield optimization by varying the microalgae growth conditions make them favorable producers of EVs for biotechnology and biomedical application. Full article
(This article belongs to the Section Plant Cell Biology)
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38 pages, 12524 KiB  
Article
Therapeutic Efficacy of Plant-Derived Exosomes for Advanced Scar Treatment: Quantitative Analysis Using Standardized Assessment Scales
by Lidia Majewska, Agnieszka Kondraciuk, Iwona Paciepnik, Agnieszka Budzyńska and Karolina Dorosz
Pharmaceuticals 2025, 18(8), 1103; https://doi.org/10.3390/ph18081103 - 25 Jul 2025
Viewed by 863
Abstract
Background: Wound healing and scar management remain significant challenges in dermatology and aesthetic medicine. Recent advances in regenerative medicine have introduced plant-derived exosome-like nanoparticles (PDENs) as potential therapeutic agents due to their bioactive properties. This study examines the clinical application of rose [...] Read more.
Background: Wound healing and scar management remain significant challenges in dermatology and aesthetic medicine. Recent advances in regenerative medicine have introduced plant-derived exosome-like nanoparticles (PDENs) as potential therapeutic agents due to their bioactive properties. This study examines the clinical application of rose stem cell exosomes (RSCEs) in combination with established treatments for managing different types of scars. Methods: A case series of four patients with different scar etiologies (dog bite, hot oil burn, forehead trauma, and facial laser treatment complications) was treated with RSCEs in combination with microneedling (Dermapen 4.0, 0.2–0.4 mm depth) and/or thulium laser therapy (Lutronic Ultra MD, 8–14 J), or as a standalone topical treatment. All cases underwent sequential treatments over periods ranging from two to four months, with comprehensive photographic documentation of the progression. The efficacy was assessed through clinical photography and objective evaluation using the modified Vancouver Scar Scale (mVSS) and the Patient and Observer Scar Assessment Scale (POSAS), along with assessment of scar appearance, texture, and coloration. Results: All cases demonstrated progressive improvement throughout the treatment course. The dog bite scar showed significant objective improvement, with a 71% reduction in modified Vancouver Scar Scale score (from 7/13 to 2/13) and a 61% improvement in Patient and Observer Scar Assessment Scale scores after four combined treatments. The forehead trauma case exhibited similar outcomes, with a 71% improvement in mVSS score and 55–57% improvement in POSAS scores. The hot oil burn case displayed the most dramatic improvement, with a 78% reduction in mVSS score and over 70% improvement in POSAS scores, resulting in near-complete resolution without visible scarring. The facial laser complication case showed a 75% reduction in mVSS score and ~70% improvement in POSAS scores using only topical exosome application without device-based treatments. Clinical improvements across all cases included reduction in elevation, improved texture, decreased erythema, and better integration with surrounding skin. No adverse effects were reported in any of the cases. Conclusions: This preliminary case series suggests that plant-derived exosome-like nanoparticles, specifically rose stem cell exosomes (RSCEs), may enhance scar treatment outcomes when combined with microneedling and laser therapy, or even as a standalone topical treatment. The documented objective improvements, measured by standardized scar assessment scales, along with clinical enhancements in scar appearance, texture, and coloration across different scar etiologies—dog bite, burn, traumatic injury, and iatrogenic laser damage—suggest that this approach may offer a valuable addition to the current armamentarium of scar management strategies. Notably, the successful treatment of laser-induced complications using only topical exosome application demonstrates the versatility and potential of this therapeutic modality. Full article
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31 pages, 4179 KiB  
Review
Plant-Derived Vesicle-like Nanoparticles: Pioneering Sustainable and Effective Approaches for Tissue Repair and Regeneration
by Qinjing Wang, Zhijie Huang, Jiming Guo, Weixing Chen, Min Wang, Yue Ming, Hongyu Liu, Mingshu Huang, Yisheng Huang, Zhengming Tang and Bo Jia
Biomolecules 2025, 15(8), 1055; https://doi.org/10.3390/biom15081055 - 22 Jul 2025
Viewed by 601
Abstract
Plant-derived vesicle-like nanoparticles (PDVLNs) are bioactive nanovesicles secreted by plant cells, emerging as a novel therapeutic tool for tissue repair and regeneration due to their low immunogenicity, intrinsic bioactivity, and potential as drug delivery carriers. This review examines PDVLNs’ biogenesis mechanisms, isolation techniques, [...] Read more.
Plant-derived vesicle-like nanoparticles (PDVLNs) are bioactive nanovesicles secreted by plant cells, emerging as a novel therapeutic tool for tissue repair and regeneration due to their low immunogenicity, intrinsic bioactivity, and potential as drug delivery carriers. This review examines PDVLNs’ biogenesis mechanisms, isolation techniques, and compositional diversity, emphasizing their roles in promoting essential regenerative processes—cell proliferation, differentiation, migration, immune modulation, and angiogenesis. We explore their therapeutic applications across multiple tissue types, including skin, bone, neural, liver, gastrointestinal, cardiovascular, and dental tissues, using both natural and engineered PDVLNs in various disease models. Compared to mammalian exosomes, PDVLNs offer advantages such as reduced immune rejection and ethical concerns, enhancing their sustainability and appeal for regenerative medicine. However, challenges in clinical translation, including scalability, standardization, and safety remain. This paper consolidates current knowledge on PDVLNs, highlighting their versatility and providing insights into engineering strategies to optimize efficacy, ultimately outlining future research directions to advance their clinical potential. Plant vesicle-like nanoparticles (PDVLNs) may become a new avenue for the treatment of tissue injury, promoting tissue repair and regeneration through their intrinsic bioactivity or as drug delivery carriers. In addition, PDVLNs can be engineered and modified to achieve better results. Full article
(This article belongs to the Section Natural and Bio-derived Molecules)
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17 pages, 3907 KiB  
Article
Safety Validation of Plant-Derived Materials for Skin Application
by Euihyun Kim, Hyo Hyun Seo, Dong Sun Shin, Jihyeok Song, Seon Kyu Yun, Jeong Hun Lee and Sang Hyun Moh
Cosmetics 2025, 12(4), 153; https://doi.org/10.3390/cosmetics12040153 - 21 Jul 2025
Viewed by 826
Abstract
The cosmetic industry faces a critical need to balance commercial innovation with scientific validation, especially regarding the safety and efficacy of raw materials. Plant-derived materials (PDMs) offer a promising alternative to animal-derived ingredients in cosmetics, particularly due to their safety and compliance with [...] Read more.
The cosmetic industry faces a critical need to balance commercial innovation with scientific validation, especially regarding the safety and efficacy of raw materials. Plant-derived materials (PDMs) offer a promising alternative to animal-derived ingredients in cosmetics, particularly due to their safety and compliance with vegan and ethical standards. Unlike compounds such as polydeoxyribonucleotide (PDRN), which is derived from the testis or seminal fluid of Salmonidae species and raises concerns regarding its origin, sustainability, and consumer acceptability, PDMs provide a cleaner, ethically preferable profile. In this study, we evaluated 50 PDM candidates using in vitro cell viability, wound healing, and immunocytochemistry assays, along with primary skin irritation tests in human participants. None of the samples showed harmful effects. Notably, sample Nos. 38 and 42 demonstrated significant wound-healing capacity and upregulated filaggrin expression without causing notable irritation in clinical testing. These findings support the biological activity and safety of specific PDMs as functional cosmetic ingredients. This study presents scientifically validated evidence for plant-based alternatives to animal-derived materials and offers a new milestone in the shift toward sustainable and ethical cosmetic development. By bridging the gap between consumer demand and scientific rigor, this study provides a robust platform for future innovations in vegan cosmetics. Full article
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23 pages, 6291 KiB  
Article
Application of Standardized Rosa damascena Stem Cell-Derived Exosomes in Dermatological Wound Healing and Scar Management: A Retrospective Case-Series Study with Long-Term Outcome Assessment
by Lidia Majewska, Agnieszka Kondraciuk, Karolina Dorosz and Agnieszka Budzyńska
Pharmaceutics 2025, 17(7), 910; https://doi.org/10.3390/pharmaceutics17070910 - 14 Jul 2025
Cited by 2 | Viewed by 901
Abstract
Background: Scar formation and impaired wound healing represent significant challenges in dermatology and aesthetic medicine, with limited effective treatment options currently available. Objectives: To evaluate the efficacy and long-term outcomes of Damask rose stem-cell-derived exosome (RSCE) therapy in the management of [...] Read more.
Background: Scar formation and impaired wound healing represent significant challenges in dermatology and aesthetic medicine, with limited effective treatment options currently available. Objectives: To evaluate the efficacy and long-term outcomes of Damask rose stem-cell-derived exosome (RSCE) therapy in the management of diverse dermatological conditions, including traumatic wounds, surgical scars, and atrophic acne scars. Methods: We conducted a case series study from June 2023 to November 2024, documenting four cases with different types of skin damage treated with lyophilized RSCE products. Treatment protocols included a variety of delivery methods such as topical application, microneedling, and post-procedure care. Follow-up assessments were performed at intervals ranging from 7 days to 10 months. Results: All patients demonstrated significant improvements in scar appearance, skin elasticity, hydration, and overall tissue quality. In traumatic facial injury, RSCE therapy facilitated reduction in scar contracture and improved functional outcomes. For atrophic acne scars, comparative treatment of facial sides showed enhanced results with RSCE addition. Acute wounds exhibited accelerated healing with reduced inflammation, while chronic wounds demonstrated improved epithelialization and long-term scar quality. Conclusions: This case series provides preliminary evidence suggesting that RSCE therapy may offer significant benefits in wound healing and scar management. The observed improvements in tissue regeneration, inflammatory modulation, and long-term aesthetic outcomes warrant further investigation through controlled clinical trials. Full article
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33 pages, 3277 KiB  
Review
Plant-Derived Exosomes: Nano-Inducers of Cross-Kingdom Regulations
by Touseef Ur Rehman, Huiliang Li, Maria Martuscelli, Francesca Aiello, Luigi Esposito, Kamran Ashraf, Meijin Guo and Ali Mohsin
Pharmaceuticals 2025, 18(7), 1005; https://doi.org/10.3390/ph18071005 - 4 Jul 2025
Viewed by 1103
Abstract
Exosomes are essential components produced by all cell types, originating from the endosomal pathway through the invagination of the cell membrane. Their unique physicochemical characteristics are crucial for various commercial applications. Typically, exosomes range in size from 50 to 200 nm. Exosomes derived [...] Read more.
Exosomes are essential components produced by all cell types, originating from the endosomal pathway through the invagination of the cell membrane. Their unique physicochemical characteristics are crucial for various commercial applications. Typically, exosomes range in size from 50 to 200 nm. Exosomes derived from plant cells are larger than their animal cell counterparts and demonstrate a broader therapeutic potential. This review explores the promising research opportunities associated with plant-derived exosomes, summarizing studies on their biogenesis, characterization, isolation methods, and therapeutic applications. It also emphasizes the importance of targeted drug delivery and provides insights into engineering plant-derived exosomes with various drugs. Additionally, highlights of plant-derived exosomes as natural nano-inducers that facilitate inter-kingdom communication and cross-kingdom regulatory interactions are also elucidated herein. Henceforth, this study culminates in a multidimensional insight for innovative therapeutic strategies and biotechnological advancements in plant-derived exosome research. Full article
(This article belongs to the Section Biopharmaceuticals)
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31 pages, 1265 KiB  
Review
Plant-Derived Exosomes: Carriers and Cargo of Natural Bioactive Compounds: Emerging Functions and Applications in Human Health
by Sorur Yazdanpanah, Silvia Romano, Anna Valentino, Umberto Galderisi, Gianfranco Peluso and Anna Calarco
Nanomaterials 2025, 15(13), 1005; https://doi.org/10.3390/nano15131005 - 30 Jun 2025
Viewed by 1229
Abstract
Extracellular vesicles (EVs) have gained increasing attention in recent years as a valuable focus of scientific investigation, owing to their potential therapeutic properties and wide-ranging uses in medicine. EVs are a heterogeneous population of membrane-enclosed vesicles with lipid bilayers, released by cells from [...] Read more.
Extracellular vesicles (EVs) have gained increasing attention in recent years as a valuable focus of scientific investigation, owing to their potential therapeutic properties and wide-ranging uses in medicine. EVs are a heterogeneous population of membrane-enclosed vesicles with lipid bilayers, released by cells from both animal and plant origins. These widespread vesicles play a crucial role in cell-to-cell communication and serve as carriers for a variety of biomolecules such as proteins, lipids, and nucleic acids. The most common method of classifying EVs is based on their biogenesis pathway, distinguishing exosomes, microvesicles, and apoptotic bodies as the major types. In recent years, there has been a growing interest in PDEs, as they offer a practical and eco-friendly alternative to exosomes sourced from mammals. Mounting data from both laboratory-based and animal model experiments indicate that PDEs have natural therapeutic properties that modulate biological activities within cells, demonstrating properties such as anti-inflammatory, antioxidant, and anticancer effects that may aid in treating diseases and enhancing human well-being. Moreover, PDEs hold promise as reliable and biologically compatible carriers for drug delivery. Although studies conducted before clinical trials have yielded encouraging results, numerous unresolved issues and gaps in understanding remain, which must be resolved to facilitate the effective advancement of PDEs toward medical use in human patients. A key concern is the absence of unified procedures for processing materials and for obtaining PDEs from different botanical sources. This article provides a comprehensive summary of existing findings on PDEs, critically examining the hurdles they face, and highlighting their substantial promise as a novel class of therapeutic tools for a range of illnesses. Full article
(This article belongs to the Section Biology and Medicines)
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31 pages, 1043 KiB  
Review
Targeted Delivery Strategies for Hydrophilic Phytochemicals
by Marta Sharafan, Anna Dziki, Magdalena Anna Malinowska, Elżbieta Sikora and Agnieszka Szopa
Appl. Sci. 2025, 15(13), 7101; https://doi.org/10.3390/app15137101 - 24 Jun 2025
Cited by 1 | Viewed by 594
Abstract
Hydrophilic phytochemicals, such as flavonoids and phenolic acids, possess important biological activities, including antioxidant, anti-inflammatory, and anticancer effects. However, their application is hindered by low membrane permeability, poor chemical stability, and limited skin penetration. This review provides a comprehensive analysis of advanced delivery [...] Read more.
Hydrophilic phytochemicals, such as flavonoids and phenolic acids, possess important biological activities, including antioxidant, anti-inflammatory, and anticancer effects. However, their application is hindered by low membrane permeability, poor chemical stability, and limited skin penetration. This review provides a comprehensive analysis of advanced delivery strategies aimed at enhancing the solubility, bioavailability, and therapeutic efficacy of selected hydrophilic compounds. Specifically, it focuses on the encapsulation of flavonoids such as quercetin, luteolin, and apigenin, as well as phenolic acids including ferulic acid, caffeic acid, and chlorogenic acid. The review discusses various nanocarrier systems: liposomes, niosomes, exosomes, and polymeric nanoparticles (e.g., nanocapsules, nanospheres) and compares their structural characteristics, preparation methods, and functional benefits. These delivery systems improve the physicochemical stability of active compounds, enable controlled and targeted release, and enhance skin and cellular absorption. Despite certain challenges related to large-scale production and regulatory constraints, such approaches offer promising solutions for the pharmaceutical and cosmetic application of hydrophilic plant-derived compounds. Full article
(This article belongs to the Special Issue Applications of Nanocarriers for Phytochemical Delivery)
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18 pages, 3320 KiB  
Article
Isolation and Bioactive Characterization of Berberis kaschgarica Rupr-Derived Exosome-Like Nanovesicles: Exploring Therapeutic Potential in Atherosclerosis Pathogenesis
by Dilihuma Dilimulati, Nuerbiye Nueraihemaiti, Alhar Baishan, Sendaer Hailati, Alifeiye Aikebaier, Yipaerguli Paerhati and Wenting Zhou
Biology 2025, 14(6), 726; https://doi.org/10.3390/biology14060726 - 19 Jun 2025
Viewed by 607
Abstract
Berberis kaschgarica Rupr.-derived exosome-like nanovesicles (BELNs), a type of plant-derived extracellular vesicle, consist of proteins, lipids, and nucleic acids. In this research, we employed differential centrifugation and ultracentrifugation techniques to isolate and purify BELNs. Subsequently, we conducted a comprehensive multi-omics analysis to systematically [...] Read more.
Berberis kaschgarica Rupr.-derived exosome-like nanovesicles (BELNs), a type of plant-derived extracellular vesicle, consist of proteins, lipids, and nucleic acids. In this research, we employed differential centrifugation and ultracentrifugation techniques to isolate and purify BELNs. Subsequently, we conducted a comprehensive multi-omics analysis to systematically determine their physicochemical properties. Experiments were conducted in vitro with Human Umbilical Vein Endothelial Cells (HUVECs) to verify the therapeutic impact of BELNSs on atherosclerosis. The isolated BELNs exhibited a distinctive teacup-shaped exosome morphology. The extraction yield was approximately 2.1 × 1013 particles per milliliter, and the average particle size was measured to be 179.1 nm. These nanovesicles were lipid-rich. The protein content predominantly comprised cytoplasmic proteins. In-depth analysis revealed the presence of five highly conserved plant microRNAs: miR166, miR156, miR399, miR171, and miR395. These miRNAs are involved in regulating plant growth and responses to both biotic and abiotic stresses. Functional assays demonstrated that Berberis kaschgarica Rupr.-derived exosome-like nanovesicles substantially decreased the lipid deposition in HUVECs that was triggered by Palmitic Acid (PA). This research establishes the inaugural utilization of multi-omics platforms to systematically elucidate the bioactivity profile of BELNs from Berberis kaschgarica Rupr., thereby laying the groundwork for advancing its therapeutic potential. Full article
(This article belongs to the Special Issue Plant Natural Products: Mechanisms of Action for Promoting Health)
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19 pages, 4208 KiB  
Article
Plant-Derived Nanovesicles from Soaked Rice Water: A Novel and Sustainable Platform for the Delivery of Natural Anti-Oxidant γ-Oryzanol
by Jahnavi Ravilla, Soundaram Rajendran, Vidya M. Basavaraj, Greeshma Satheeshan, Janakiraman Narayanan, Thejaswini Venkatesh and Gopinath M. Sundaram
Antioxidants 2025, 14(6), 717; https://doi.org/10.3390/antiox14060717 - 12 Jun 2025
Viewed by 985
Abstract
Gamma oryzanol (GO) is a natural anti-oxidant found in rice bran with potential health benefits. Conventional isolation of GO from rice bran requires the use of non-eco-friendly solvents such as acetone, ethyl acetate and hexane due to its low aqueous solubility. Further, nanoencapsulation [...] Read more.
Gamma oryzanol (GO) is a natural anti-oxidant found in rice bran with potential health benefits. Conventional isolation of GO from rice bran requires the use of non-eco-friendly solvents such as acetone, ethyl acetate and hexane due to its low aqueous solubility. Further, nanoencapsulation of GO is required for the enhancement of stability and bioavailability. Plant-derived nanovesicles (PDNVs) are natural/intrinsic exosome-mimetic vesicles isolated from edible plants using green methods. Washed/soaked rice water (SRW) is often discarded as waste prior to cooking rice. However, traditional knowledge indicates its health-promoting anti-oxidant benefit, probably contributed by the presence of GO. Herein, for the first time, we isolated PDNVs from SRW by the cost-effective Polyethylene glycol 6000(PEG) precipitation method and demonstrated the presence of GO in PDNVs. In our initial screen, PDNVs were isolated from both rice grains (RGs) as well as the SRW of four different rice varieties, in which we identified the copious presence of GO in black RGs and brown SRW PDNVs. Both RG and SRW PDNVs were non-toxic to keratinocytes. SRW PDNVs displayed distinct cellular uptake mechanisms compared to RG PDNVs in human keratinocytes. Compared to native GO, brown SRW PDNVs containing GO displayed superior anti-oxidant activity in HaCaT keratinocytes, likely due to its enhanced cellular uptake. Overall, we describe here a waste-to-wealth green approach using an economical PEG method for the extraction of GO in bioavailable form. Given that oxidative stress is a driving factor for inflammation and related diseases, SRW PDNVs provide an affordable natural formulation for the treatment of diseases with underlying oxidative stress and inflammation. Full article
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20 pages, 2737 KiB  
Article
Natural Nanoparticles for Drug Delivery: Proteomic Insights and Anticancer Potential of Doxorubicin-Loaded Avocado Exosomes
by Dina Salem, Shaimaa Abdel-Ghany, Eman Mohamed, Nada F. Alahmady, Amany Alqosaibi, Ibtesam S. Al-Dhuayan, Mashael Mashal Alnamshan, Rebekka Arneth, Borros Arneth and Hussein Sabit
Pharmaceuticals 2025, 18(6), 844; https://doi.org/10.3390/ph18060844 - 4 Jun 2025
Viewed by 1072
Abstract
Background: Exosomes have recently attracted significant attention for their potential in drug delivery. Plant-derived exosomes, in particular, may serve as direct anticancer agents due to their unique characteristics, including immunogenicity, biocompatibility, safety, cell-free nature, and nanoscale structure. Methods: This study characterizes [...] Read more.
Background: Exosomes have recently attracted significant attention for their potential in drug delivery. Plant-derived exosomes, in particular, may serve as direct anticancer agents due to their unique characteristics, including immunogenicity, biocompatibility, safety, cell-free nature, and nanoscale structure. Methods: This study characterizes Persea americana (avocado)-derived exosomes, exploring their anticancer properties, proteomic profile, and therapeutic potential. Results: Isolated exosomes exhibited a diameter of 99.58 ± 5.09 nm (non-loaded) and 151.2 ± 6.36 nm (doxorubicin (DOX)-loaded), with zeta potentials of −17 mV and −28 mV, respectively. Proteomic analysis identified 47 proteins, including conserved exosome markers (GAPDH, tubulin) and stress-response proteins (defensin, endochitinase). Functional enrichment revealed roles in photosynthesis, glycolysis, ATP synthesis, and transmembrane transport, supported by protein–protein interaction networks highlighting energy metabolism and cellular trafficking. DOX encapsulation efficiency was 18%, with sustained release (44.4% at 24 h). In vitro assays demonstrated reduced viability in breast cancer (MCF-7, T47D, 4T1) and endothelial (C166) cells, enhanced synergistically by DOX (Av+DOX). Gene expression analysis revealed cell-specific modulation: Av+DOX upregulated TP53 and STAT in T47D but suppressed both in 4T1/C166, suggesting context-dependent mechanisms. Conclusions: These findings underscore avocado exosomes as promising nanovehicles for drug delivery, combining biocompatibility, metabolic functionality, and tunable cytotoxicity. Their plant-derived origin offers a scalable, low-cost alternative to mammalian exosomes, with potential applications in oncology and targeted therapy. Further optimization of loading efficiency and in vivo validation are warranted to advance translational prospects. Full article
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19 pages, 1704 KiB  
Review
Harnessing Mammalian- and Plant-Derived Exosomes for Drug Delivery: A Comparative Review
by Shynggys Sergazy, Sergazy Adekenov, Ilya Khabarov, Kymbat Adekenova, Assiya Maikenova and Mohamad Aljofan
Int. J. Mol. Sci. 2025, 26(10), 4857; https://doi.org/10.3390/ijms26104857 - 19 May 2025
Cited by 1 | Viewed by 2141
Abstract
Exosomes, nanoscale vesicles involved in intercellular communication, have garnered significant attention for their potential in drug delivery and therapeutic applications. This review provides a comparative analysis of mammalian-derived exosomes, particularly milk-derived exosomes, and plant-derived exosome-like nanoparticles (PDENs). It explores their biogenesis, bioactivities, and [...] Read more.
Exosomes, nanoscale vesicles involved in intercellular communication, have garnered significant attention for their potential in drug delivery and therapeutic applications. This review provides a comparative analysis of mammalian-derived exosomes, particularly milk-derived exosomes, and plant-derived exosome-like nanoparticles (PDENs). It explores their biogenesis, bioactivities, and functional similarities, including their roles in cellular communication, immune modulation, and disease therapy. While milk-derived exosomes exhibit promising biocompatibility and stability for targeted delivery, PDENs offer distinct advantages, such as scalability and inherent bioactivities, derived from their plant sources. Despite similarities in their structure and cargo, PDENs differ in lipid composition and protein profiles, reflecting plant-specific functions. Emerging research highlights the therapeutic potential of PDENs in managing inflammation, oxidative stress, and other diseases, emphasizing their utility as functional food components and nanocarriers. However, challenges related to their chemical stability and large-scale production require further investigation. This review underscores the need for advanced studies to fully harness the potential of these natural nanocarriers in drug-delivery systems and therapeutic interventions. Full article
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