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Exosomes in Medicine: Recent Advances in Drug Delivery, Diagnostics, and...
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Exosomes in Medicine: Recent Advances in Drug Delivery, Diagnostics, and Therapeutics

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Gene and Cell Therapy".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 15388

Special Issue Editor

Prof. Dr. Vetriselvan Subramaniyan

E-Mail Website
Guest Editor
Department of Biomedical Sciences, Faculty of Medical and Life Sciences, Sir Jeffrey Cheah Sunway Medical School, Sunway University, Bandar Sunway, Petaling Jaya 47500, Selangor, Malaysia
Interests: exosome-based drug delivery systems; precision medicine; molecular diagnostics; inflammation; bioavailability; lipid metabolism; immunomodulation; neuroprotection; translational pharmacology; personalized medicine

Special Issue Information

Dear Colleagues,

Exosomes—nano-sized extracellular vesicles released by cells—have emerged as significant facilitators of intercellular communication, with potential implications in contemporary medicine. This Special Issue aims to highlight recent advances in the understanding of exosomes and their utilization in drug delivery, disease diagnostics, and therapeutic interventions. Exosomes, due to their inherent biocompatibility, capacity to transport bioactive compounds, and potential for tailored delivery, constitute a revolutionary platform in precision medicine. This Issue solicits original research articles, reviews, and brief communications centered on the extraction, characterization, and engineering of exosomes for clinical and translational purposes. Key study areas of interest encompass exosome-mediated drug- and gene-delivery systems, the function of exosomes as diagnostic biomarkers in oncology and metabolic disorders, and their therapeutic potential in inflammation, neurodegeneration, and immunological regulation. Research that combines exosomes with phytochemicals, nanomaterials, or biomaterials to improve efficacy and specificity is also recommended. This Issue seeks to enhance exosome research by integrating diverse viewpoints and fostering the advancement of innovative solutions for disease management and personalized healthcare.

Prof. Dr. Vetriselvan Subramaniyan
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • exosomes
  • drug delivery
  • diagnostics
  • therapeutics
  • precision medicine
  • biomarkers
  • nanomedicine
  • inflammation and neurodegeneration
  • exosome engineering
  • translational research

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Published Papers (6 papers)

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Research

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17 pages, 4386 KB  
Article
Mesenchymal Stem Cell–Derived Exosomes Mitigate Cutaneous Radiation Injury Through Coordinated Modulation of DNA Repair, Stress, and Inflammatory Gene Programs
by Amanda Ringwood, Chi Zhang and Rob Knight
Biomedicines 2026, 14(4), 811; https://doi.org/10.3390/biomedicines14040811 - 2 Apr 2026
Viewed by 1767
Abstract
Background: Cutaneous radiation injury arises when ionizing radiation disrupts epidermal barrier integrity, triggering persistent DNA damage, oxidative stress, and senescence-associated inflammatory signaling that drive extracellular matrix degradation and impaired regeneration. Clinical burden is rising due to dose-intensified radiotherapy, but also due to [...] Read more.
Background: Cutaneous radiation injury arises when ionizing radiation disrupts epidermal barrier integrity, triggering persistent DNA damage, oxidative stress, and senescence-associated inflammatory signaling that drive extracellular matrix degradation and impaired regeneration. Clinical burden is rising due to dose-intensified radiotherapy, but also due to an increased use of energy-based aesthetic procedures that elicit radiation-like dermal injury. Dermal fibroblasts exhibit marked sensitivity to ionizing radiation and rapidly acquire senescence-associated secretory phenotypes that suppress collagen biosynthesis and promote chronic inflammation, underpinning the need for regenerative treatments that restore tissue homeostasis and regenerative competence. Mesenchymal stem cell–derived exosomes have emerged as a promising therapeutic strategy in this setting, with increasing preclinical evidence demonstrating their capacity to attenuate oxidative stress, enhance DNA damage-repair pathways, and normalize fibroblast metabolic function. Methods: In this study, we examine the expression profiles for 14 radiation response–associated genes of irradiated human dermal fibroblasts that were treated with bone marrow and umbilical cord MSC-derived exosomes at different timepoints using quantitative RT-PCR analysis. We also explore functional relationships among these genes through interaction network analysis, and outline a framework to organize pathway-level transcriptional responses to irradiation and exosome treatment. Results: MSC-derived exosome treatment was associated with attenuated early damage response signaling at 24 h, followed by increased expression of genes associated with DNA repair and oxidative stress recovery at intermediate timepoints. Exosome-treated cells also exhibited transcriptional changes consistent with modulation of cell-cycle regulatory pathways and reduced expression of pro-inflammatory markers by 5 d. These findings suggest that MSC-derived exosomes influence the temporal organization of the fibroblast transcriptional response to ionizing radiation and may contribute to molecular programs associated with tissue recovery following ionizing radiation exposure. Full article
(This article belongs to the Special Issue Exosomes in Medicine: Recent Advances in Drug Delivery, Diagnostics, and Therapeutics)
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15 pages, 2172 KB  
Article
Comparative Proteomics of Seminal Exosomes Reveals Size-Exclusion Chromatography Outperforms Ultracentrifugation
by Ajaya K. Moharana, Manesh Kumar Panner Selvam, Soumya Ranjan Jena, Partha K. Chandra, David W. Busija, Luna Samanta and Suresh C. Sikka
Biomedicines 2025, 13(10), 2459; https://doi.org/10.3390/biomedicines13102459 - 9 Oct 2025
Cited by 2 | Viewed by 3152
Abstract
Background: Extracellular vesicles, particularly exosomes, play a crucial role in cell–cell communication and as carriers of biomarkers. However, their use in clinical settings is limited due to a lack of standardized isolation and characterization. Ultracentrifugation (UC) is considered a gold standard for [...] Read more.
Background: Extracellular vesicles, particularly exosomes, play a crucial role in cell–cell communication and as carriers of biomarkers. However, their use in clinical settings is limited due to a lack of standardized isolation and characterization. Ultracentrifugation (UC) is considered a gold standard for exosome isolation but presents several limitations. Size-exclusion chromatography (SEC) has recently gained attention as a superior method, which offers better yield, purity, and protection of exosome physical properties. This study focused on optimizing the SEC method for isolation of exosomes from seminal plasma and comparing yield, quality, and proteome profiles with those obtained by UC. Methods: In this SEC method, seminal plasma (0.5 mL) was loaded onto a SEC column and collected in 13 fractions of 0.4 mL each. The physical and molecular characterization of exosomes was carried out using a ZetaView analyzer and Western blot, respectively. Further, SEC-isolated exosomes were used for proteomic profiling and functional bioinformatic analysis. Results: The second and third fractions had the highest concentration of exosomes with uniform size and strong expression of exosome markers. Also, comparative proteomic analysis identified 3315 proteins in SEC-isolated exosomes and 931 in UC-isolated exosomes, with 709 proteins in common. SEC-isolated exosomes showed greater overlap with Vesiclepedia’s and ExoCarta’s top 100 lists than UC-isolated exosomes (Vesiclepedia: 91 vs. 77 proteins, ExoCarta: 94 vs. 79). Proteins from SEC- and UC-isolated exosomes showed similar enrichment profiles across all three gene ontology categories. Conclusions: Overall, this optimized SEC protocol is a reliable alternative method to isolate seminal exosomes with high purity, supporting its potential applications in clinical and basic research. Full article
(This article belongs to the Special Issue Exosomes in Medicine: Recent Advances in Drug Delivery, Diagnostics, and Therapeutics)
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Review

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32 pages, 2087 KB  
Review
Collecting Eggs, Not Killing Chickens: Why Stem Cell Secretome and Exosomes Are Redefining Regenerative Medicine for Healthspan Extension
by John A. Dangerfield and Christoph Metzner
Biomedicines 2026, 14(4), 854; https://doi.org/10.3390/biomedicines14040854 - 9 Apr 2026
Viewed by 1003
Abstract
Regenerative medicine is becoming more widely integrated with longevity-oriented and preventive care as populations age and chronic degenerative diseases burden healthcare systems. Mesenchymal stem cell (MSC) therapies have progressed from experimental interventions to approved products, yet scalability, safety, cost, and regulatory complexity constrain [...] Read more.
Regenerative medicine is becoming more widely integrated with longevity-oriented and preventive care as populations age and chronic degenerative diseases burden healthcare systems. Mesenchymal stem cell (MSC) therapies have progressed from experimental interventions to approved products, yet scalability, safety, cost, and regulatory complexity constrain widespread implementation in medical wellness contexts. The predominant therapeutic effects of MSCs are mediated via paracrine mechanisms, leading to cell-free approaches based on the MSC secretome—a complex mixture of bioactive factors including all types of biomolecules and assemblies thereof, such as exosomes. These acellular products offer compelling advantages: multiple batches from single-donor sources, standardized dosing, reduced allogeneic cell risks, and shorter outpatient-compatible administration. Preclinical and clinical data indicate that secretome-based products exert potent regenerative effects in osteoarthritis, chronic wounds, stroke, traumatic brain injury, and neurodegenerative diseases. This review examines the evolution from cell-based to cell-free regenerative strategies, focusing on human umbilical cord Wharton’s jelly MSC secretome for precision longevity medicine. It compares MSC therapies with secretome- and exosome-based formulations across mechanistic, manufacturing, safety, practical and regulatory dimensions. Regional perspectives highlight Southeast Asia, and especially Thailand, as an emerging regenerative-longevity hub. Finally, it outlines the preventive patient journey integrating cell-free interventions within multi-modal programs aimed at extending healthspan. Full article
(This article belongs to the Special Issue Exosomes in Medicine: Recent Advances in Drug Delivery, Diagnostics, and Therapeutics)
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27 pages, 2546 KB  
Review
Extracellular Vesicles: A Comprehensive Review of Their Origins, Functions, and Therapeutic Potential
by Madison B. Schank, Juan Zhao, Ling Wang, Jonathan P. Moorman and Zhi Q. Yao
Biomedicines 2026, 14(3), 495; https://doi.org/10.3390/biomedicines14030495 - 25 Feb 2026
Cited by 2 | Viewed by 2370
Abstract
Extracellular vesicles (EVs) are membrane-bound particles secreted by most cell types that play a pivotal role in intercellular communication via transporting protein, nucleic acid, lipid, and metabolite cargos. Among EVs, exosomes are a well-characterized subtype, typically ranging from 10–150 nm in diameter and [...] Read more.
Extracellular vesicles (EVs) are membrane-bound particles secreted by most cell types that play a pivotal role in intercellular communication via transporting protein, nucleic acid, lipid, and metabolite cargos. Among EVs, exosomes are a well-characterized subtype, typically ranging from 10–150 nm in diameter and originating from the endosomal pathway via the formation of multivesicular bodies that fuse with the plasma membrane. EVs/exosomes can be isolated from various biological fluids and cultured cells, with production and yield influenced by the cell type and culture conditions. Isolation methods, including ultracentrifugation or density-based ultracentrifugation, tangential flow filtration, size-exclusion chromatography, immunoaffinity and membrane-affinity capture, and recently developed commercial equipment, offer distinct advantages and limitations in terms of purity, scalability, and exosome integrity. Characterization techniques, such as nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), cryogenic electron microscopy (cryo-EM), atomic force microscopy (AFM), Western blotting, flow cytometry, and dynamic light scattering (DLS), assess exosome size, morphology, and biomarker expression. Given their biocompatibility and inherent targeting capabilities across a diverse range of diseases, EVs/exosomes hold clinical promise as diagnostic biomarkers, cell-free therapeutics, drug delivery vehicles, immune modulators, and in regenerative medicine. However, these emerging fields in exosome medicine continue to face challenges in standardizing EV sourcing, production, purification, yield, bio-targeting, drug loading, and drug delivery. While EVs/exosomes represent a rapidly advancing frontier in biomedical science, robust protocols for standardization and scalable production will be essential for their successful translation into clinical applications. This article provides a comprehensive overview of EV/exosome origins, their biological functions, the approaches for their isolation and characterization, and their therapeutic potential. Full article
(This article belongs to the Special Issue Exosomes in Medicine: Recent Advances in Drug Delivery, Diagnostics, and Therapeutics)
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14 pages, 1267 KB  
Review
Human Blood Exosomes: Isolation and Characterization Methods, Variability, and the Need for Standardized Protocols—A Review
by Elena Sánchez-Vizcaíno Mengual, Laura Cordero and Hernán Pinto
Biomedicines 2025, 13(12), 2970; https://doi.org/10.3390/biomedicines13122970 - 3 Dec 2025
Cited by 7 | Viewed by 2491
Abstract
Background/Objectives: As bioactive extracellular vesicles, exosomes participate in cellular communication and disease mechanisms, yet their structural complexity continues to challenge standard analytical methodologies. This review summarizes published studies reporting exosome concentrations in human plasma, serum, and platelet-rich plasma from healthy individuals and [...] Read more.
Background/Objectives: As bioactive extracellular vesicles, exosomes participate in cellular communication and disease mechanisms, yet their structural complexity continues to challenge standard analytical methodologies. This review summarizes published studies reporting exosome concentrations in human plasma, serum, and platelet-rich plasma from healthy individuals and highlights methodological differences. Methods: A comprehensive PubMed search (1986–31 August 2025) was performed using terms related to exosomes and their quantification, excluding cancer- and disease-related studies. Eligible articles reported exosome concentrations in plasma, serum, or platelet-rich plasma using particle-counting techniques such as nanoparticle tracking analysis, flow cytometry, or tunable resistive pulse sensing. Results: Twenty-two articles, including 167 healthy donors, met the inclusion criteria. The following mean concentration ranges were reported: plasma (n = 18), ranged from 4.50 × 108 to 6.70 × 1011 particles/mL with differences by quantification method; serum (n = 10), from 5.30 × 108 to 2.13 × 1011 particles/mL; non-activated platelet-rich plasma (n = 1), 7.52 × 109 particles/mL; activated platelet-rich plasma (n = 3), 4.87 × 1010 to 7.16 × 1010 particles/mL; and preconditioned platelet-rich plasma with photothermal biomodulation (n = 2), 2.53 × 1011 to 2.99 × 1011 particles/mL. Conclusions: Isolation and quantification methods exhibit high variability, which strongly influences the overall quantity and quality of the exosomes obtained. Characteristics, including cargo composition, purity, and exosome integrity, must be considered when developing validated methods. Furthermore, emerging evidence suggests that PTBM preconditioning can increase exosome release from cells. In summary, rigorous standardization of protocols is essential to advance the scientific understanding and the clinical potential of exosome-based therapies. Full article
(This article belongs to the Special Issue Exosomes in Medicine: Recent Advances in Drug Delivery, Diagnostics, and Therapeutics)
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26 pages, 2493 KB  
Review
Dendritic Cell-Derived Exosomes: Next Generation of Cancer Immunotherapy
by Rajib Dhar, Swarup Sonar, Asmit Das, Nur Aliaa Sorfina Tajul Akmal, Ainil Hawa Jasni, Vinod RMT Balasubramaniam, Kumaran Narayanan and Vetriselvan Subramaniyan
Biomedicines 2025, 13(10), 2497; https://doi.org/10.3390/biomedicines13102497 - 14 Oct 2025
Cited by 6 | Viewed by 3871
Abstract
Dendritic cells (DCs) are the most highlighted cell population for cancer immunotherapy development. Currently, DC-derived exosomes show promising anti-cancer activity. Exosomes are a subpopulation of extracellular vesicles (EVs) and originate from endosomes. It transports dynamic molecular cargos such as DNA, RNA, protein, and [...] Read more.
Dendritic cells (DCs) are the most highlighted cell population for cancer immunotherapy development. Currently, DC-derived exosomes show promising anti-cancer activity. Exosomes are a subpopulation of extracellular vesicles (EVs) and originate from endosomes. It transports dynamic molecular cargos such as DNA, RNA, protein, and lipid. This cellular cargo exchange reprograms the recipient cell naturally. In cancer research, DC-derived exosomes (DEXs) are used as a therapeutic tool. There are some approaches followed in the application of DEX in cancer as a therapeutic tool. DEX-based drug delivery, tumor antigen-loaded DEX, and modified DEX are applicable approaches in cancer therapy. DEXs are biocompatible, nontoxic, and have ability-specific targeting. On the other hand, this method faces some challenges, such as large-scale production, isolation, and heterogeneity. A multidisciplinary approach (advanced nanotechnology, multi-omics, and single-exosome profiling) comes up with a solution to this issue. This review provides a comprehensive overview of the DEX approach, tracing its developmental journey and therapeutic application in cancer immunotherapy. It examines key findings from clinical trials and outlines the challenges and future research directions in this field, ultimately underscoring the potential of DC-derived exosomes as a research-backed, cell-free solution for the next generation of cancer immunotherapies. Full article
(This article belongs to the Special Issue Exosomes in Medicine: Recent Advances in Drug Delivery, Diagnostics, and Therapeutics)
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