Journal Article

FZJ-2020-03203

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The Basement Membrane in a 3D Breast Acini Model Modulates Delivery and Anti-Proliferative Effects of Liposomal Anthracyclines

Wiedenhoeft, T. ; Braun, T. ; Springer, R.FZJ* ; Teske, M. ; Noetzel, E.FZJ* ; Merkel, R.FZJ* ; Csiszar, A. (Corresponding author)FZJ*

2020
MDPI Basel

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Please use a persistent id in citations: http://hdl.handle.net/2128/25697  doi:10.3390/ph13090256

Abstract: 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

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Contributing Institute(s):

1. Mechanobiologie (IBI-2)

Research Program(s):

1. 552 - Engineering Cell Function (POF3-552) (POF3-552)

Appears in the scientific report 2020

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Database coverage:
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