Extracellular Vesicles as Surrogates for Drug Metabolism and Clearance: Promise vs. Reality.

Life (Basel)

Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.

Published: August 2023

Drug-metabolizing enzymes (DMEs) and transporters play a major role in drug efficacy and safety. They are regulated at multiple levels and by multiple factors. Estimating their expression and activity could contribute to predicting drug pharmacokinetics and their regulation by drugs or pathophysiological situations. Determining the expression of these proteins in the liver, intestine, and kidney requires the collection of biopsy specimens. Instead, the isolation of extracellular vesicles (EVs), which are nanovesicles released by most cells and present in biological fluids, could deliver this information in a less invasive way. In this article, we review the use of EVs as surrogates for the expression and activity of DMEs, uptake, and efflux transporters. Preliminary evidence has been provided for a correlation between the expression of some enzymes and transporters in EVs and the tissue of origin. In some cases, data obtained in EVs reflect the induction of phase I-DMEs in the tissues. Further studies are required to elucidate to what extent the regulation of other DMEs and transporters in the tissues reflects in the EV cargo. If an association between tissues and their EVs is firmly established, EVs may represent a significant advancement toward precision therapy based on the biotransformation and excretion capacity of each individual.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10455864PMC
http://dx.doi.org/10.3390/life13081745DOI Listing

Publication Analysis

Top Keywords

extracellular vesicles
8
dmes transporters
8
expression activity
8
evs
6
vesicles surrogates
4
surrogates drug
4
drug metabolism
4
metabolism clearance
4
clearance promise
4
promise reality
4

Similar Publications

Extracellular vesicles from pancreatic cancer and its tumour microenvironment promote increased Schwann cell migration.

Br J Cancer

January 2025

Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Background: Pancreatic ductal adenocarcinoma (PDAC) exhibits a high frequency of neural invasion (NI). Schwann cells (SCs) have been shown to be reprogrammed to facilitate cancer cell migration and invasion into nerves. Since extracellular vesicles (EVs) affect the tumour microenvironment and promote metastasis, the present study analysed the involvement of EVs from pancreatic cancer cells and their microenvironment in altering SC phenotype as part of the early events in the process of NI.

View Article and Find Full Text PDF

CAFs-released exosomal CREB1 promotes cell progression and immune evasion in thyroid cancer via the positive regulation of CCL20.

Autoimmunity

December 2025

Department of Thyroid Head and Neck Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.

Background: Exosomes derived from cancer-associated fibroblasts (CAFs) can affect tumor microenvironment (TME) of thyroid cancer (TC). The cAMP response element binding protein 1 (CREB1) acts as a transcription factor to participate in cancer development. Currently, we aimed to explore the molecular mechanism of exosome-associated CREB1 and C-C motif chemokine ligand 20 (CCL20) in TC.

View Article and Find Full Text PDF

Platelet extracellular vesicles-loaded hydrogel bandages for personalized wound care.

Trends Biotechnol

January 2025

Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Shuang-Ho Campus, New Taipei City 235603, Taiwan; International PhD Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Shuang-Ho Campus, New Taipei City 235603, Taiwan; International PhD Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan. Electronic address:

Autologous or allogeneic platelet-derived extracellular vesicles (pEVs) show potential in enhancing tissue recovery and healing chronic wounds. pEVs promote neovascularization and cell migration while reducing inflammation, oxidative stress, and scarring. However, their efficacy in clinical settings is challenged by their susceptibility to washout by wound exudate.

View Article and Find Full Text PDF

Validation of an automated quality control method to test sterility of two advanced therapy medicinal products: Mesenchymal stromal cells and their extracellular vesicles.

Hematol Transfus Cell Ther

November 2024

Hospital São Rafael, Salvador, Bahia, Brazil; Instituto D'Or de Pesquisa e Ensino (IDOR), Salvador, Bahia, Brazil; Instituto Gonçalo Moniz, FIOCRUZ, Salvador, Bahia, Brazil. Electronic address:

Mesenchymal stromal cells are multipotent cells present in various tissues that are widely studied for relevant therapeutic potential due to their paracrine immunomodulatory and tissue regenerating properties. Many mesenchymal stromal cell-based products are under investigation for the treatment of different clinical conditions. Recently, the therapeutic potential of the extracellular vesicles released by these cells has been under focus, with emphasis on clinical translation.

View Article and Find Full Text PDF

Mapping organism-wide single cell mRNA expression linked to extracellular vesicle biogenesis, secretion and cargo.

Function (Oxf)

January 2025

Department of Health and Exercise Science, College of Health and Human Sciences, Colorado State University, Fort Collins, CO, USA.

Extracellular vesicles (EVs) are functional lipid-bound nanoparticles trafficked between cells and found in every biofluid. It is widely claimed that EVs can be secreted by every cell, but the quantity and composition of these EVs can differ greatly among cell types and tissues. Defining this heterogeneity has broad implications for EV-based communication in health and disease.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!