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Life
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Innovative Applications of Extracellular Vesicles: From Diagnostics to Drug Delivery
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Innovative Applications of Extracellular Vesicles: From Diagnostics to Drug Delivery

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Physiology and Pathology".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 17145

Special Issue Editor

Dr. Alessandra Lo Cicero

E-Mail Website
Guest Editor
Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, Ed. 16, 90128 Palermo, Italy
Interests: extracellular vesicles; exosomes; cancer biochemistry; tumor microenvironment; drug delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Extracellular vesicles (EVs) have received much scientific attention throughout the last decade as mediators of a newly discovered cell-to-cell communication system, acting over short and long distances. EVs are generated by the blebbing of the plasma membrane (microvesicles) formed in multivesicular bodies to be secreted by exocytosis as exosomes. Exosomes, microvesicles, and other EVs carry a wide range of cargo, including proteins, lipids, and RNAs. This composition can differ based on their site of biogenesis, making them rich sources of biomarkers for various diseases.

In diagnostics, EVs are extremely valuable due to their ability to reflect the physiological and pathological state of their cells of origin. The molecular cargo of EVs can provide detailed information about the presence and stage of diseases such as cancer, neurodegenerative disorders, and cardiovascular diseases. They can be isolated from bodily fluids, providing non-invasive methods for early disease detection, monitoring disease progression, and tailoring personalized treatment strategies.

Due to their biocompatibility, stability, lower immunogenicity, and unique features, EVs are widely explored as drug delivery systems, showing promising results in preclinical studies. EVs can be engineered to deliver therapeutic agents, including small molecules, proteins, and nucleic acids, directly to target cells.

This Special Issue aims to discuss recent advances in the field of EVs and their role as mediators of intercellular communication in pathological conditions, highlighting their potential innovative strategies for significant advancements in therapeutics and diagnostics.

Dr. Alessandra Lo Cicero
Guest Editor

Manuscript Submission Information

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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. Life 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

  • extracellular vesicles
  • exosomes
  • cancer
  • cardiovascular diseases
  • neurodegenerative diseases
  • biomarkers
  • diagnostics
  • cell-cell communication
  • drug delivery
  • therapeutics

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Published Papers (4 papers)

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Research

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27 pages, 5458 KB  
Article
Therapeutic Potential of Astrocyte-Derived Extracellular Vesicles in Post-Stroke Recovery: Behavioral and MRI-Based Insights from a Rat Model
by Yessica Heras-Romero, Axayácatl Morales-Guadarrama, Luis B. Tovar-y-Romo, Diana Osorio Londoño, Roberto Olayo-González and Ernesto Roldan-Valadez
Life 2025, 15(9), 1418; https://doi.org/10.3390/life15091418 - 9 Sep 2025
Viewed by 1258
Abstract
Astrocyte-derived extracellular vesicles (ADEVs) have emerged as promising neuroprotective agents for ischemic stroke. In this study, we evaluated the therapeutic potential of hypoxia-conditioned ADEVs (HxEVs) administered intracerebroventricularly in a rat model of transient middle cerebral artery occlusion (tMCAO). Serial magnetic resonance imaging (MRI) [...] Read more.
Astrocyte-derived extracellular vesicles (ADEVs) have emerged as promising neuroprotective agents for ischemic stroke. In this study, we evaluated the therapeutic potential of hypoxia-conditioned ADEVs (HxEVs) administered intracerebroventricularly in a rat model of transient middle cerebral artery occlusion (tMCAO). Serial magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) was performed at 1, 7, 14, and 21 days post-stroke. HxEV treatment produced a significant reduction in infarct volume from day 1, sustained through day 21, and was accompanied by improvements in motor and sensory recovery. DTI analyses showed progressive normalization of fractional anisotropy (FA) and radial diffusivity (RD), particularly in the corpus callosum and striatum, reflecting microstructural repair. In contrast, mean diffusivity (MD) was less sensitive to these treatment effects. Regional differences in therapeutic response were evident, with earlier and more sustained recovery in the corpus callosum than in other brain regions. Histological findings confirmed greater preservation of dendrites and axons in HxEV-treated animals, supporting the role of these vesicles in accelerating post-stroke neurorepair. Together, these results demonstrate that hypoxia-conditioned ADEVs promote both structural and functional recovery after ischemic stroke. They also highlight the value of DTI-derived biomarkers as non-invasive tools to monitor neurorepair. The identification of region-specific therapeutic effects and the validation of reliable imaging markers provide a strong foundation for future research and development. Full article
(This article belongs to the Special Issue Innovative Applications of Extracellular Vesicles: From Diagnostics to Drug Delivery)
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20 pages, 1865 KB  
Article
Trophoblast Extracellular Vesicles as Modulators of Keratinocyte Stress Response and Senescence
by Mirjana Nacka-Aleksić, Andrea Pirković, Aleksandra Vilotić, Maja Kosanović, Dragana Dekanski, Janko Legner and Milica Jovanović Krivokuća
Life 2025, 15(6), 918; https://doi.org/10.3390/life15060918 - 5 Jun 2025
Viewed by 1604
Abstract
Keratinocyte stress, caused by various intrinsic and extrinsic factors, contributes to the overall aging process. D-galactose-induced metabolic/oxidative stress is a commonly used in vitro model for studying premature aging. Due to their rich composition of bioactive molecules that influence critical pathways in cellular [...] Read more.
Keratinocyte stress, caused by various intrinsic and extrinsic factors, contributes to the overall aging process. D-galactose-induced metabolic/oxidative stress is a commonly used in vitro model for studying premature aging. Due to their rich composition of bioactive molecules that influence critical pathways in cellular aging and rejuvenation, placental derivatives have a well-established history in anti-aging skincare and therapy. However, trophoblast-derived extracellular vesicle (TEV) effects on D-galactose-induced premature aging in keratinocytes have not been investigated yet. TEV pretreatment for 24 h enhanced cellular resilience against D-galactose-induced stress, judging by the downregulated expression of senescence- and stress-associated markers (p19 and p21, HIF-1α, mTOR), and reduced production of reactive oxygen species and DNA damage. Additionally, TEV pretreatment enhanced keratinocyte proliferation and integrin-β1 subunit expression upon D-galactose exposure, most likely contributing to more efficient wound closure. In conclusion, this study underscores the potential of TEVs to modify expression of stress- and senescence-related proteins in keratinocytes and improve their wound healing properties. Their regenerative and protective characteristics position TEVs as promising candidates for developing innovative procedures to address skin conditions related to premature aging. Full article
(This article belongs to the Special Issue Innovative Applications of Extracellular Vesicles: From Diagnostics to Drug Delivery)
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11 pages, 1253 KB  
Article
Comparison of Methods for Isolating Exosomes from Plasma Subjects with Normal and High Fat Percentages
by Jacqueline Noboa-Velástegui, Juan Carlos León, Jorge Castro, Ana Fletes, Perla Madrigal, Iñaki Álvarez and Rosa Navarro
Life 2025, 15(3), 410; https://doi.org/10.3390/life15030410 - 6 Mar 2025
Cited by 3 | Viewed by 3898
Abstract
Adipose tissue is responsible for fat storage and is an important producer of extracellular vesicles (EVs). The biological content of exosomes, one kind of EV, provides information on aspects such as immunometabolic alterations. This study aimed to compare three plasma exosome isolation methods—using [...] Read more.
Adipose tissue is responsible for fat storage and is an important producer of extracellular vesicles (EVs). The biological content of exosomes, one kind of EV, provides information on aspects such as immunometabolic alterations. This study aimed to compare three plasma exosome isolation methods—using a commercial kit (CK), size exclusion chromatography (SEC), and differential centrifugation (DC)—and select the best one. Individuals categorized by normal and high body fat percentages were used. The DC and CK were proven to be the most advantageous out of the exosome isolation methods, so we suggest these methods for further protein and molecular analyses, respectively. Still, we emphasize the importance of selecting an appropriate methodology depending on the specific research objectives. At the same time, no statistical differences in exosome quality, morphology, total protein, or microRNA concentration were observed between individuals categorized by body fat percentage, so we suggest that the exosomal cargo varies in individuals with normal and high fat percentages. Full article
(This article belongs to the Special Issue Innovative Applications of Extracellular Vesicles: From Diagnostics to Drug Delivery)
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Review

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30 pages, 3595 KB  
Review
Extracellular Vesicles as Tools for Crossing the Blood–Brain Barrier to Treat Lysosomal Storage Diseases
by Giovanni Lerussi, Verónica Villagrasa-Araya, Marc Moltó-Abad, Mireia del Toro, Guillem Pintos-Morell, Joaquin Seras-Franzoso and Ibane Abasolo
Life 2025, 15(1), 70; https://doi.org/10.3390/life15010070 - 9 Jan 2025
Cited by 7 | Viewed by 9448
Abstract
Extracellular vesicles (EVs) are nanosized, membrane-bound structures that have emerged as promising tools for drug delivery, especially in the treatment of lysosomal storage disorders (LSDs) with central nervous system (CNS) involvement. This review highlights the unique properties of EVs, such as their biocompatibility, [...] Read more.
Extracellular vesicles (EVs) are nanosized, membrane-bound structures that have emerged as promising tools for drug delivery, especially in the treatment of lysosomal storage disorders (LSDs) with central nervous system (CNS) involvement. This review highlights the unique properties of EVs, such as their biocompatibility, capacity to cross the blood–brain barrier (BBB), and potential for therapeutic cargo loading, including that of enzymes and genetic material. Current therapies for LSDs, like enzyme replacement therapy (ERT), often fail to address neurological symptoms due to their inability to cross the BBB. EVs offer a viable alternative, allowing for targeted delivery to the CNS and improving therapeutic outcomes. We discuss recent advancements in the engineering and modification of EVs to enhance targeting, circulation time and cargo stability, and provide a detailed overview of their application in LSDs, such as Gaucher and Fabry diseases, and Sanfilippo syndrome. Despite their potential, challenges remain in scaling production, ensuring isolation purity, and meeting regulatory requirements. Future developments will focus on overcoming these barriers, paving the way for the clinical translation of EV-based therapies in LSDs and other CNS disorders. Full article
(This article belongs to the Special Issue Innovative Applications of Extracellular Vesicles: From Diagnostics to Drug Delivery)
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