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7.9
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Pharmaceutics
Special Issues
Targeting Cell Junctions for Therapy and Delivery
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Targeting Cell Junctions for Therapy and Delivery

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

Deadline for manuscript submissions: closed (30 December 2023) | Viewed by 11017

Special Issue Editors

Dr. Brian Belardi

E-Mail Website
Guest Editor
McKetta Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USA
Interests: cell contact and adhesion; extracellular matrix; synthetic biology; chemical biology; therapeutics; biophysics
Prof. Dr. Michael Koval

E-Mail Website
Guest Editor
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
Interests: intercellular interactions; tight junctions; integrins; super-resolution microscopy; nanotechnology; epithelial cells

Special Issue Information

Dear Colleagues,

I am pleased to invite you to submit manuscripts for a Special Issue in Pharmaceutics, focused on targeting cell junctions for therapy and delivery. Cell junctions integrate cells within a tissue, enabling long-range communication, collective action, tissue surveillance, and protective maintenance. Beyond mere connections, junctions have recently emerged as critical hubs for cellular decision-making functions, with dysfunctional organization and interactions leading to disease progression and cell death. This Special Issue highlights work on the frontier of designing molecules, materials, and interventions that target junctional components and their cellular organization. In doing so, junctions can be manipulated to reinforce their integrity or disrupt their function. The latter is particularly important for improving the delivery of therapeutics to their site of action. The articles that belong to this issue will showcase how junctions can be manipulated for therapeutic purposes and how delivery can be improved.

This Special Issue aims to highlight new pharmaceutical methodologies and materials which alter the junctional state, both directly—by acting on junctional molecules—and indirectly—by causing cell-wide responses. The scope of the issue also encompasses research on optimized assays for characterizing the state of junctions and their function within tissue. Both original research articles and reviews are welcome.

We look forward to receiving your contributions.

Dr. Brian Belardi
Prof. Dr. Michael Koval
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 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • barrier function
  • adhesion
  • permeability
  • cell Junctions
  • membrane receptors
  • membrane trafficking
  • cytoskeleton attachment
  • mechanotransduction
  • biologics
  • nanotechnology

Published Papers (4 papers)

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Research

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23 pages, 7793 KiB  
Article
cCPE Fusion Proteins as Molecular Probes to Detect Claudins and Tight Junction Dysregulation in Gastrointestinal Cell Lines, Tissue Explants and Patient-Derived Organoids
by Ayk Waldow, Laura-Sophie Beier, Janine Arndt, Simon Schallenberg, Claudia Vollbrecht, Philip Bischoff, Martí Farrera-Sal, Florian N. Loch, Christian Bojarski, Michael Schumann, Lars Winkler, Carsten Kamphues, Lukas Ehlen and Jörg Piontek
Pharmaceutics 2023, 15(7), 1980; https://doi.org/10.3390/pharmaceutics15071980 - 19 Jul 2023
Cited by 2 | Viewed by 1534
Abstract
Claudins regulate paracellular permeability, contribute to epithelial polarization and are dysregulated during inflammation and carcinogenesis. Variants of the claudin-binding domain of Clostridium perfringens enterotoxin (cCPE) are highly sensitive protein ligands for generic detection of a broad spectrum of claudins. Here, we investigated the [...] Read more.
Claudins regulate paracellular permeability, contribute to epithelial polarization and are dysregulated during inflammation and carcinogenesis. Variants of the claudin-binding domain of Clostridium perfringens enterotoxin (cCPE) are highly sensitive protein ligands for generic detection of a broad spectrum of claudins. Here, we investigated the preferential binding of YFP- or GST-cCPE fusion proteins to non-junctional claudin molecules. Plate reader assays, flow cytometry and microscopy were used to assess the binding of YFP- or GST-cCPE to non-junctional claudins in multiple in vitro and ex vivo models of human and rat gastrointestinal epithelia and to monitor formation of a tight junction barrier. Furthermore, YFP-cCPE was used to probe expression, polar localization and dysregulation of claudins in patient-derived organoids generated from gastric dysplasia and gastric cancer. Live-cell imaging and immunocytochemistry revealed cell polarity and presence of tight junctions in glandular organoids (originating from intestinal-type gastric cancer and gastric dysplasia) and, in contrast, a disrupted diffusion barrier for granular organoids (originating from discohesive tumor areas). In sum, we report the use of cCPE fusion proteins as molecular probes to specifically and efficiently detect claudin expression, localization and tight junction dysregulation in cell lines, tissue explants and patient-derived organoids of the gastrointestinal tract. Full article
(This article belongs to the Special Issue Targeting Cell Junctions for Therapy and Delivery)
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16 pages, 2996 KiB  
Article
The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn’s Disease but Not Ulcerative Colitis Patients
by Young Su Park, Sang Bum Kang, Ronald R. Marchelletta, Harrison M. Penrose, Roos Ruiter-Visser, Barbara Jung, Michael J. Docherty, Brigid S. Boland, William J. Sandborn and Declan F. McCole
Pharmaceutics 2023, 15(3), 811; https://doi.org/10.3390/pharmaceutics15030811 - 2 Mar 2023
Cited by 2 | Viewed by 1736
Abstract
The prostone analog, lubiprostone, is approved to manage constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in animal models of colitis. The aim of this study was to determine if lubiprostone improves barrier properties in isolated colonic biopsies from Crohn’s [...] Read more.
The prostone analog, lubiprostone, is approved to manage constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in animal models of colitis. The aim of this study was to determine if lubiprostone improves barrier properties in isolated colonic biopsies from Crohn’s disease (CD) and ulcerative colitis (UC) patients. Sigmoid colon biopsies from healthy subjects, CD and UC patients in remission, and CD patients with active disease were mounted in Ussing chambers. Tissues were treated with lubiprostone or vehicle to determine the effects on transepithelial electrical resistance (TER), FITC-dextran 4kD (FD4) permeability, and electrogenic ion transport responses to forskolin and carbachol. Localization of the tight junction protein, occludin, was determined by immunofluorescence. Lubiprostone significantly increased ion transport across control, CD and UC remission biopsies but not active CD. Lubiprostone selectively improved TER in both CD remission and active disease biopsies but not in control or UC biopsies. The improved TER was associated with increased membrane localization of occludin. Lubiprostone selectively improved barrier properties of biopsies from CD patients vs. UC and independent of an ion transport response. These data indicate that lubiprostone has potential efficacy in improving mucosal integrity in Crohn’s disease. Full article
(This article belongs to the Special Issue Targeting Cell Junctions for Therapy and Delivery)
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12 pages, 1823 KiB  
Article
Tumor Treating Fields (TTFields) Induce Cell Junction Alterations in a Human 3D In Vitro Model of the Blood-Brain Barrier
by Ellaine Salvador, Theresa Köppl, Julia Hörmann, Sebastian Schönhärl, Polina Bugaeva, Almuth F. Kessler, Malgorzata Burek, Ralf-Ingo Ernestus, Mario Löhr and Carsten Hagemann
Pharmaceutics 2023, 15(1), 185; https://doi.org/10.3390/pharmaceutics15010185 - 4 Jan 2023
Cited by 11 | Viewed by 2377
Abstract
In a recent study, we showed in an in vitro murine cerebellar microvascular endothelial cell (cerebEND) model as well as in vivo in rats that Tumor-Treating Fields (TTFields) reversibly open the blood–brain barrier (BBB). This process is facilitated by delocalizing tight junction proteins [...] Read more.
In a recent study, we showed in an in vitro murine cerebellar microvascular endothelial cell (cerebEND) model as well as in vivo in rats that Tumor-Treating Fields (TTFields) reversibly open the blood–brain barrier (BBB). This process is facilitated by delocalizing tight junction proteins such as claudin-5 from the membrane to the cytoplasm. In investigating the possibility that the same effects could be observed in human-derived cells, a 3D co-culture model of the BBB was established consisting of primary microvascular brain endothelial cells (HBMVEC) and immortalized pericytes, both of human origin. The TTFields at a frequency of 100 kHz administered for 72 h increased the permeability of our human-derived BBB model. The integrity of the BBB had already recovered 48 h post-TTFields, which is earlier than that observed in cerebEND. The data presented herein validate the previously observed effects of TTFields in murine models. Moreover, due to the fact that human cell-based in vitro models more closely resemble patient-derived entities, our findings are highly relevant for pre-clinical studies. Full article
(This article belongs to the Special Issue Targeting Cell Junctions for Therapy and Delivery)
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Review

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32 pages, 1245 KiB  
Review
Airway Epithelial Cell Junctions as Targets for Pathogens and Antimicrobial Therapy
by Nannan Gao and Fariba Rezaee
Pharmaceutics 2022, 14(12), 2619; https://doi.org/10.3390/pharmaceutics14122619 - 27 Nov 2022
Cited by 9 | Viewed by 4010
Abstract
Intercellular contacts between epithelial cells are established and maintained by the apical junctional complexes (AJCs). AJCs conserve cell polarity and build epithelial barriers to pathogens, inhaled allergens, and environmental particles in the respiratory tract. AJCs consist of tight junctions (TJs) and adherens junctions [...] Read more.
Intercellular contacts between epithelial cells are established and maintained by the apical junctional complexes (AJCs). AJCs conserve cell polarity and build epithelial barriers to pathogens, inhaled allergens, and environmental particles in the respiratory tract. AJCs consist of tight junctions (TJs) and adherens junctions (AJs), which play a key role in maintaining the integrity of the airway barrier. Emerging evidence has shown that different microorganisms cause airway barrier dysfunction by targeting TJ and AJ proteins. This review discusses the pathophysiologic mechanisms by which several microorganisms (bacteria and viruses) lead to the disruption of AJCs in airway epithelial cells. We present recent progress in understanding signaling pathways involved in the formation and regulation of cell junctions. We also summarize the potential chemical inhibitors and pharmacological approaches to restore the integrity of the airway epithelial barrier. Understanding the AJCs–pathogen interactions and mechanisms by which microorganisms target the AJC and impair barrier function may further help design therapeutic innovations to treat these infections. Full article
(This article belongs to the Special Issue Targeting Cell Junctions for Therapy and Delivery)
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