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Pharmaceutics
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Extracellular Vesicles for Targeted Delivery
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Extracellular Vesicles for Targeted Delivery

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biologics and Biosimilars".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 2959

Special Issue Editor

Dr. Beáta Soltész

E-Mail Website
Guest Editor
Department of Human Genetics, Faculty of Medicine, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary
Interests: clinical application of liquid biopsy; exosomes; nucleic acids (e.g., gDNA, mtDNA, miRNA, and lncRNA) and cell-free nucleic acids; molecular biology; genetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Extracellular vesicles (EVs), mainly exosomes, are more applicable in the early detection, characterization, and monitoring of various diseases. EVs are packed with several molecules, which may affect cell-to-cell communication after release. Therefore, these are ideal candidates for delivering molecules such as nucleic acids, proteins, and designed drugs. The modified and engineered exosomes may become star delivery vehicles and the importance of these in therapy may be highlighted. We may gather worthwhile information from EVs to understand their role in the progression of distinct diseases and in treatment options as carrying cargo to the target cells. Several beneficial properties of EVs make them promising therapeutic shuttle vesicles, and therefore, personalized medicine made from engineered extracellular vesicles may be a new treatment option for various diseases.

This Special Issue aims to address the latest research or new views on extracellular vesicles in the monitoring, characterizing, and understanding of background mechanisms, and thus, possible therapeutic applications.

Dr. Beáta Soltész
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. 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

  • computational approaches
  • drug delivery
  • engineered exosomes
  • exosomes
  • experimental approaches
  • extracellular vesicle-based delivery
  • extracellular vesicles
  • immunotherapy
  • nanomedicine
  • therapeutic cargo
  • therapy

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Published Papers (2 papers)

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Research

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27 pages, 6020 KB  
Article
Engineered Nanobody-Bearing Extracellular Vesicles Enable Precision Trop2 Knockdown in Resistant Breast Cancer
by Jassy Mary S. Lazarte, Mounika Aare, Sandeep Chary Padakanti, Arvind Bagde, Aakash Nathani, Zachary Meeks, Li Sun, Yan Li and Mandip Singh
Pharmaceutics 2025, 17(10), 1318; https://doi.org/10.3390/pharmaceutics17101318 - 11 Oct 2025
Viewed by 426
Abstract
Background/Objectives: Trophoblast cell surface antigen 2 (Trop2), a transmembrane glycoprotein overexpressed in a broad spectrum of epithelial malignancies but minimally expressed in normal tissues, has emerged as a clinically relevant prognostic biomarker and therapeutic target, particularly in breast cancer. This study aims [...] Read more.
Background/Objectives: Trophoblast cell surface antigen 2 (Trop2), a transmembrane glycoprotein overexpressed in a broad spectrum of epithelial malignancies but minimally expressed in normal tissues, has emerged as a clinically relevant prognostic biomarker and therapeutic target, particularly in breast cancer. This study aims to develop an enhanced way of targeting Trop2 expression in tumors and blocking it using extracellular vesicles (EVs) bioengineered to express a nanobody sequence against Trop2 (NB60 E). Methods: Here, a plasmid construct was designed to express the Trop2 sequence, NB60, flanked with HA tag and myc epitope and a PDGFR transmembrane domain in the C-terminal region, and was transfected into HEK293T cells for EVs isolation. The potency of NB60 E to knock down Trop2 in letrozole-resistant breast cancer cells (LTLT-Ca and MDA-MB-468 cells) was initially investigated. Thereafter, the effects of NB60 E on the cell viability and downstream signaling pathway of Trop2 via MTT assay and Western blotting were determined. Lastly, we also examined whether NB60 E treatment in Jurkat T cells affects IL-6, TNF-α, and IL-2 cytokine production by enzyme-linked immunosorbent assay (ELISA). Results: Results revealed treatment with NB60 E significantly reduced surface Trop2 expression across both cell lines by 23.5 ± 1.5% in MDA-MB-468, and 61.5 ± 1.5% in LTLT-Ca, relative to the HEK293T-derived control EVs (HEK293T E). NB60 E treatment resulted in a marked reduction in LTLT-Ca cell viability by 52.8 ± 0.9% at 48 h post-treatment. This was accompanied by downregulation of key oncogenic signaling molecules: phosphorylated ERK1/2 (p-ERK 1/2) decreased by 30 ± 4%, cyclin D1 by 67 ± 11%, phosphorylated STAT3 (p-STAT3) by 71.8 ± 1.6%, and vimentin by 40.8 ± 1.4%. ELISA analysis revealed significant decreases in IL-6 (−57.5 ± 1.5%, 7.4 ± 0.35 pg/mL) and TNF-α (−32.1 ± 0.3%, 6.1 ± 1.2 pg/mL) levels, coordinated by an increase in IL-2 secretion (22.1 ± 2.7%, 49.2 ± 1.1 pg/mL). Quantitative analysis showed marked reductions in the number of nodes (−45 ± 4.4%), junctions (−55 ± 3.5%), and branch points (−38 ± 1.2%), indicating suppression of angiogenic capacity. In vivo experiment using near-infrared Cy7 imaging demonstrated rapid and tumor-selective accumulation of NB60 E within 4 h post-administration, followed by efficient systemic clearance by 24 h. The in vivo results demonstrate the effectiveness of NB60 E in targeting Trop2-enriched tumors while being efficiently cleared from the system, thus minimizing off-target interactions with normal cells. Lastly, Trop2 expression in LTLT-Ca tumor xenografts revealed a significant reduction of 41.0 ± 4% following NB60 E treatment, confirming efficient targeted delivery. Conclusions: We present a first-in-field NB60 E-grafted EV therapy that precisely homes to Trop2-enriched breast cancers, silences multiple growth-and-invasion pathways, blocks angiogenesis, and rewires cytokine crosstalk, achieving potent antitumor effects with self-clearing, biomimetic carriers. Our results here show promising potential for the use of NB60 E as anti-cancer agents, not only for letrozole-resistant breast cancer but also for other Trop2-expressing cancers. Full article
(This article belongs to the Special Issue Extracellular Vesicles for Targeted Delivery)
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Review

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22 pages, 1826 KB  
Review
Nanomanaging Chronic Wounds with Targeted Exosome Therapeutics
by Anita Yadav, Anu Sharma, Mohini Moulick and Subhadip Ghatak
Pharmaceutics 2025, 17(3), 366; https://doi.org/10.3390/pharmaceutics17030366 - 13 Mar 2025
Cited by 3 | Viewed by 2055
Abstract
Chronic wounds pose a significant healthcare challenge, impacting millions of patients worldwide and burdening healthcare systems substantially. These wounds often occur as comorbidities and are prone to infections. Such infections hinder the healing process, complicating clinical management and proving recalcitrant to therapy. The [...] Read more.
Chronic wounds pose a significant healthcare challenge, impacting millions of patients worldwide and burdening healthcare systems substantially. These wounds often occur as comorbidities and are prone to infections. Such infections hinder the healing process, complicating clinical management and proving recalcitrant to therapy. The environment within the wound itself poses challenges such as lack of oxygen, restricted blood flow, oxidative stress, ongoing inflammation, and bacterial presence. Traditional systemic treatment for such chronic peripheral wounds may not be effective due to inadequate blood supply, resulting in unintended side effects. Furthermore, topical applications are often impervious to persistent biofilm infections. A growing clinical concern is the lack of effective therapeutic modalities for treating chronic wounds. Additionally, the chemically harsh wound microenvironment can reduce the effectiveness of treatments, highlighting the need for drug delivery systems that can deliver therapies precisely where needed with optimal dosages. Compared to cell-based therapies, exosome-based therapies offer distinct advantages as a cell-free approach for chronic wound treatment. Exosomes are of endosomal origin and enable cell-to-cell communications, and they possess benefits, including biocompatibility and decreased immunogenicity, making them ideal vehicles for efficient targeting and minimizing off-target damage. However, exosomes are rapidly cleared from the body, making it difficult to maintain optimal therapeutic concentrations at wound sites. The hydrogel-based approach and development of biocompatible scaffolds for exosome-based therapies can be beneficial for sustained release and prolong the presence of these therapeutic exosomes at chronic wound sites. Engineered exosomes have been shown to possess stability and effectiveness in promoting wound healing compared to their unmodified counterparts. Significant progress has been made in this field, but further research is essential to unlock their clinical potential. This review seeks to explore the benefits and opportunities of exosome-based therapies in chronic wounds, ensuring sustained efficacy and precise delivery despite the obstacles posed by the wound environment. Full article
(This article belongs to the Special Issue Extracellular Vesicles for Targeted Delivery)
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