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...
Autores principales: | , , , , , , |
---|---|
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 |