Cargando…

The Basement Membrane in a 3D Breast Acini Model Modulates Delivery and Anti-Proliferative Effects of Liposomal Anthracyclines

Breast cancer progression is marked by cancer cell invasion and infiltration, which can be closely linked to sites of tumor-connected basement membrane thinning, lesion, or infiltration. Bad treatment prognosis frequently accompanies lack of markers for targeted therapy, which brings traditional che...

Descripción completa

Detalles Bibliográficos
Autores principales: Wiedenhoeft, Tabea, Braun, Tobias, Springer, Ronald, Teske, Michael, Noetzel, Erik, Merkel, Rudolf, Csiszár, Agnes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558514/
https://www.ncbi.nlm.nih.gov/pubmed/32961780
http://dx.doi.org/10.3390/ph13090256
_version_ 1783594655269519360
author Wiedenhoeft, Tabea
Braun, Tobias
Springer, Ronald
Teske, Michael
Noetzel, Erik
Merkel, Rudolf
Csiszár, Agnes
author_facet Wiedenhoeft, Tabea
Braun, Tobias
Springer, Ronald
Teske, Michael
Noetzel, Erik
Merkel, Rudolf
Csiszár, Agnes
author_sort Wiedenhoeft, Tabea
collection PubMed
description Breast cancer progression is marked by cancer cell invasion and infiltration, which can be closely linked to sites of tumor-connected basement membrane thinning, lesion, or infiltration. Bad treatment prognosis frequently accompanies lack of markers for targeted therapy, which brings traditional chemotherapy into play, despite its adverse effects like therapy-related toxicities. In the present work, we compared different liposomal formulations for the delivery of two anthracyclines, doxorubicin and aclacinomycin A, to a 2D cell culture and a 3D breast acini model. One formulation was the classical phospholipid liposome with a polyethylene glycol (PEG) layer serving as a stealth coating. The other formulation was fusogenic liposomes, a biocompatible, cationic, three-component system of liposomes able to fuse with the plasma membrane of target cells. For the lysosome entrapment-sensitive doxorubicin, membrane fusion enabled an increased anti-proliferative effect in 2D cell culture by circumventing the endocytic route. In the 3D breast acini model, this process was found to be limited to cells beneath a thinned or compromised basement membrane. In acini with compromised basement membrane, the encapsulation of doxorubicin in fusogenic liposomes increased the anti-proliferative effect of the drug in comparison to a formulation in PEGylated liposomes, while this effect was negligible in the presence of intact basement membranes.
format Online
Article
Text
id pubmed-7558514
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-75585142020-10-26 The Basement Membrane in a 3D Breast Acini Model Modulates Delivery and Anti-Proliferative Effects of Liposomal Anthracyclines Wiedenhoeft, Tabea Braun, Tobias Springer, Ronald Teske, Michael Noetzel, Erik Merkel, Rudolf Csiszár, Agnes Pharmaceuticals (Basel) Article Breast cancer progression is marked by cancer cell invasion and infiltration, which can be closely linked to sites of tumor-connected basement membrane thinning, lesion, or infiltration. Bad treatment prognosis frequently accompanies lack of markers for targeted therapy, which brings traditional chemotherapy into play, despite its adverse effects like therapy-related toxicities. In the present work, we compared different liposomal formulations for the delivery of two anthracyclines, doxorubicin and aclacinomycin A, to a 2D cell culture and a 3D breast acini model. One formulation was the classical phospholipid liposome with a polyethylene glycol (PEG) layer serving as a stealth coating. The other formulation was fusogenic liposomes, a biocompatible, cationic, three-component system of liposomes able to fuse with the plasma membrane of target cells. For the lysosome entrapment-sensitive doxorubicin, membrane fusion enabled an increased anti-proliferative effect in 2D cell culture by circumventing the endocytic route. In the 3D breast acini model, this process was found to be limited to cells beneath a thinned or compromised basement membrane. In acini with compromised basement membrane, the encapsulation of doxorubicin in fusogenic liposomes increased the anti-proliferative effect of the drug in comparison to a formulation in PEGylated liposomes, while this effect was negligible in the presence of intact basement membranes. MDPI 2020-09-19 /pmc/articles/PMC7558514/ /pubmed/32961780 http://dx.doi.org/10.3390/ph13090256 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wiedenhoeft, Tabea
Braun, Tobias
Springer, Ronald
Teske, Michael
Noetzel, Erik
Merkel, Rudolf
Csiszár, Agnes
The Basement Membrane in a 3D Breast Acini Model Modulates Delivery and Anti-Proliferative Effects of Liposomal Anthracyclines
title The Basement Membrane in a 3D Breast Acini Model Modulates Delivery and Anti-Proliferative Effects of Liposomal Anthracyclines
title_full The Basement Membrane in a 3D Breast Acini Model Modulates Delivery and Anti-Proliferative Effects of Liposomal Anthracyclines
title_fullStr The Basement Membrane in a 3D Breast Acini Model Modulates Delivery and Anti-Proliferative Effects of Liposomal Anthracyclines
title_full_unstemmed The Basement Membrane in a 3D Breast Acini Model Modulates Delivery and Anti-Proliferative Effects of Liposomal Anthracyclines
title_short The Basement Membrane in a 3D Breast Acini Model Modulates Delivery and Anti-Proliferative Effects of Liposomal Anthracyclines
title_sort basement membrane in a 3d breast acini model modulates delivery and anti-proliferative effects of liposomal anthracyclines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558514/
https://www.ncbi.nlm.nih.gov/pubmed/32961780
http://dx.doi.org/10.3390/ph13090256
work_keys_str_mv AT wiedenhoefttabea thebasementmembraneina3dbreastacinimodelmodulatesdeliveryandantiproliferativeeffectsofliposomalanthracyclines
AT brauntobias thebasementmembraneina3dbreastacinimodelmodulatesdeliveryandantiproliferativeeffectsofliposomalanthracyclines
AT springerronald thebasementmembraneina3dbreastacinimodelmodulatesdeliveryandantiproliferativeeffectsofliposomalanthracyclines
AT teskemichael thebasementmembraneina3dbreastacinimodelmodulatesdeliveryandantiproliferativeeffectsofliposomalanthracyclines
AT noetzelerik thebasementmembraneina3dbreastacinimodelmodulatesdeliveryandantiproliferativeeffectsofliposomalanthracyclines
AT merkelrudolf thebasementmembraneina3dbreastacinimodelmodulatesdeliveryandantiproliferativeeffectsofliposomalanthracyclines
AT csiszaragnes thebasementmembraneina3dbreastacinimodelmodulatesdeliveryandantiproliferativeeffectsofliposomalanthracyclines
AT wiedenhoefttabea basementmembraneina3dbreastacinimodelmodulatesdeliveryandantiproliferativeeffectsofliposomalanthracyclines
AT brauntobias basementmembraneina3dbreastacinimodelmodulatesdeliveryandantiproliferativeeffectsofliposomalanthracyclines
AT springerronald basementmembraneina3dbreastacinimodelmodulatesdeliveryandantiproliferativeeffectsofliposomalanthracyclines
AT teskemichael basementmembraneina3dbreastacinimodelmodulatesdeliveryandantiproliferativeeffectsofliposomalanthracyclines
AT noetzelerik basementmembraneina3dbreastacinimodelmodulatesdeliveryandantiproliferativeeffectsofliposomalanthracyclines
AT merkelrudolf basementmembraneina3dbreastacinimodelmodulatesdeliveryandantiproliferativeeffectsofliposomalanthracyclines
AT csiszaragnes basementmembraneina3dbreastacinimodelmodulatesdeliveryandantiproliferativeeffectsofliposomalanthracyclines