%0 Journal Article
%A Wiedenhoeft, Tabea
%A Braun, Tobias
%A Springer, Ronald
%A Teske, Michael
%A Noetzel, Erik
%A Merkel, Rudolf
%A Csiszar, Agnes
%T The Basement Membrane in a 3D Breast Acini Model Modulates Delivery and Anti-Proliferative Effects of Liposomal Anthracyclines 
%J Pharmaceuticals
%V 13
%N 9
%@ 1424-8247
%C Basel
%I MDPI
%M FZJ-2020-03203
%P 256
%D 2020
%X 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
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:32961780
%U <Go to ISI:>//WOS:000580249000001
%R 10.3390/ph13090256
%U https://juser.fz-juelich.de/record/884702