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Pharmaceutics
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Extracellular Vesicle-Based Delivery System for Cancer and Neurodegenerative Disease Treatment
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Extracellular Vesicle-Based Delivery System for Cancer and Neurodegenerative Disease Treatment

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Gene and Cell Therapy".

Deadline for manuscript submissions: 15 July 2026 | Viewed by 8041

Special Issue Editors

Dr. Eva Costanzi

E-Mail Website
Guest Editor
Dipartimento di Medicina e Chirurgia, Università degli Studi di Milano-Bicocca, Piazza dell'Ateneo Nuovo, 1-20126 Milan, Italy
Interests: extracellular vesicles; cargo; cancer
Dr. Stefano Persano

E-Mail Website
Guest Editor
Department of Oncology and Hematology-Oncology, Università degli Studi di Milano, 20122 Milano, Italy
Interests: nanovaccines; nanomaterials; cancer immunotherapy; nanomedicine; mRNA-based immunotherapy; drug and gene delivery; non-viral vectors
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Stefano Leporatti

E-Mail Website
Guest Editor
CNR NANOTEC—Istituto di Nanotecnologia, Via Monteroni, 73100 Lecce, Italy
Interests: nanomedicine; drug delivery; scanning force microscopy; cytomechanics; nanocarriers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to our Special Issue on “Extracellular Vesicle-Based Delivery System for Cancer and Neurodegenerative Disease Treatment”.

Extracellular vesicles (EVs) have emerged as promising nanocarriers capable of crossing biological barriers and delivering therapeutic agents with high specificity and reduced toxicity. The most clinically approved delivery vehicles are represented by liposomes, which are EV-like structures sharing structural similarities with EVs but differing in composition and ease of production. EVs offer greater biological complexity and potential for drug loading but face manufacturing and quality control challenges. Future applications involve the use of EV-based platforms for the delivery of immunotherapeutics, such as mRNA-based drugs. Overall, the field of EVs could be critical for advancing targeted therapies, which can significantly contribute to improving the outcomes of patients with cancer or neurodegenerative conditions.

This Special Issue aims to gather innovative research and comprehensive reviews on the development and application of EV-based delivery systems. We seek to explore the mechanisms, challenges, and clinical potential of these systems (by EVs and EV-like structures), aligning with cutting-edge therapeutic strategies and drug/gene delivery technologies.

In this Special Issue, we welcome original research articles and reviews. Research areas may include (but are not limited to) the engineering of EVs for drug delivery, therapeutic applications in cancer and neurodegenerative diseases, and clinical translation of EV-based therapies.

We look forward to receiving your contributions.

Dr. Eva Costanzi
Dr. Stefano Persano
Prof. Dr. Stefano Leporatti
Guest Editors

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. Pharmaceutics 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 2900 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
  • liposomes
  • cancer
  • neurodegenerative diseases
  • immunotherapy
  • mRNA delivery
  • drug delivery system
  • therapeutics

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Published Papers (3 papers)

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Review

34 pages, 2603 KB  
Review
Extracellular Vesicles in Alzheimer’s Disease: Dual Roles in Pathogenesis, Promising Avenues for Diagnosis and Therapy
by Feng Li, Liyang Wu, Xin Feng, Yihong Li and Huadong Fan
Pharmaceutics 2026, 18(1), 70; https://doi.org/10.3390/pharmaceutics18010070 - 5 Jan 2026
Viewed by 1762
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) plaques, neurofibrillary tau tangles, chronic neuroinflammation, and synaptic loss, leading to cognitive decline. Extracellular vesicles (EVs)—lipid bilayer nanoparticles secreted by nearly all cell types—have emerged as critical mediators [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) plaques, neurofibrillary tau tangles, chronic neuroinflammation, and synaptic loss, leading to cognitive decline. Extracellular vesicles (EVs)—lipid bilayer nanoparticles secreted by nearly all cell types—have emerged as critical mediators of intercellular communication, playing a complex dual role in both the pathogenesis and potential treatment of AD. This review generally delineates two opposite roles of EVs in pathogenesis and potential treatment of AD. On one hand, EVs derived from neurons, astrocytes, microglia and oligodendrocytes can propagate toxic proteins (Aβ, tau) and inflammatory signals, thereby accelerating disease progression. On the other hand, EVs—especially those from mesenchymal stem cells (MSCs)—exert neuroprotective effects by facilitating toxic protein clearance, modulating immune responses, preserving synaptic integrity, and alleviating oxidative stress. The cargo-carrying function of EVs gives them considerable diagnostic value. The associated cargos such as proteins and microRNAs (miRNAs) in the EVs may serve as minimally invasive biomarkers for early detection and monitoring of AD. Therapeutically, engineered EVs, including those incorporating CRISPR/Cas9-based genetic modification, are being developed as sophisticated delivery platforms for targeting core AD pathologies. Furthermore, this review highlights emerging technologies such as microfluidic chips and focused ultrasound (FUS), discussing their potential to enhance the translational prospects of EV-based early diagnostic and treatment for AD. Full article
(This article belongs to the Special Issue Extracellular Vesicle-Based Delivery System for Cancer and Neurodegenerative Disease Treatment)
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20 pages, 1129 KB  
Review
Harnessing Extracellular Vesicles for Targeted Drug Delivery in Ovarian Cancer
by Jang-Hyuk Yun, Yoo Rim Noh, Seongkyeong Yoo, Soohyun Park, Yunsup Choi, Jiyeon An and Iljin Kim
Pharmaceutics 2025, 17(4), 528; https://doi.org/10.3390/pharmaceutics17040528 - 17 Apr 2025
Cited by 3 | Viewed by 2305
Abstract
Ovarian cancer remains one of the most lethal gynecologic malignancies, primarily due to late-stage diagnosis, high recurrence rates, and the development of chemoresistance. Although targeted therapies have improved patient outcomes, their efficacy is often limited by off-target toxicity and acquired drug resistance. Extracellular [...] Read more.
Ovarian cancer remains one of the most lethal gynecologic malignancies, primarily due to late-stage diagnosis, high recurrence rates, and the development of chemoresistance. Although targeted therapies have improved patient outcomes, their efficacy is often limited by off-target toxicity and acquired drug resistance. Extracellular vesicles (EVs), nanoscale vesicles naturally released by cells, have emerged as promising carriers for precision drug delivery. This review provides a comprehensive overview of recent advances in EV-based therapeutic strategies for ovarian cancer, including the delivery of chemotherapeutic agents, nucleic acid therapeutics, and immunomodulatory molecules. We further explore innovative engineering approaches to enhance targeting specificity, such as surface modification, cell source selection, biomaterial integration, and magnetic nanoparticle-assisted delivery. Key translational challenges in bringing EV-based therapies to clinical application are also addressed. Collectively, these insights underscore the transformative potential of EV-based platforms in advancing targeted and personalized treatment for ovarian cancer. Full article
(This article belongs to the Special Issue Extracellular Vesicle-Based Delivery System for Cancer and Neurodegenerative Disease Treatment)
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Graphical abstract

29 pages, 2805 KB  
Review
Molecular Targeting of Ischemic Stroke: The Promise of Naïve and Engineered Extracellular Vesicles
by Jihun Lee, Dongho Geum, Dong-Hyuk Park and Jong-Hoon Kim
Pharmaceutics 2024, 16(12), 1492; https://doi.org/10.3390/pharmaceutics16121492 - 21 Nov 2024
Cited by 7 | Viewed by 2845
Abstract
Ischemic stroke (IS) remains a leading cause of mortality and long-term disability worldwide, with limited therapeutic options available. Despite the success of early interventions, such as tissue-type plasminogen activator administration and mechanical thrombectomy, many patients continue to experience persistent neurological deficits. The pathophysiology [...] Read more.
Ischemic stroke (IS) remains a leading cause of mortality and long-term disability worldwide, with limited therapeutic options available. Despite the success of early interventions, such as tissue-type plasminogen activator administration and mechanical thrombectomy, many patients continue to experience persistent neurological deficits. The pathophysiology of IS is multifaceted, encompassing excitotoxicity, oxidative and nitrosative stress, inflammation, and blood–brain barrier disruption, all of which contribute to neural cell death, further complicating the treatment of IS. Recently, extracellular vesicles (EVs) secreted naturally by various cell types have emerged as promising therapeutic agents because of their ability to facilitate selective cell-to-cell communication, neuroprotection, and tissue regeneration. Furthermore, engineered EVs, designed to enhance targeted delivery and therapeutic cargo, hold the potential to improve their therapeutic benefits by mitigating neuronal damage and promoting neurogenesis and angiogenesis. This review summarizes the characteristics of EVs, the molecular mechanisms underlying IS pathophysiology, and the emerging role of EVs in IS treatment at the molecular level. This review also explores the recent advancements in EV engineering, including the incorporation of specific proteins, RNAs, or pharmacological agents into EVs to enhance their therapeutic efficacy. Full article
(This article belongs to the Special Issue Extracellular Vesicle-Based Delivery System for Cancer and Neurodegenerative Disease Treatment)
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