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.
Highlights
Breast cancer occurrence is rather well monitored by the mammographic screening of females in the European Union [1]
Characterization of fusogenic liposomes (FL) and polyethylene glycol (PEG)-EL Loaded with ACL and DOX
We investigated the suitability of FL for the delivery of anti-cancer therapeutics in comparison to a liposomal drug formulation similar to liposomes already used in cancer therapy [7,28]
Summary
Breast cancer occurrence is rather well monitored by the mammographic screening of females in the European Union [1]. Breast cancer is still the most common female cancer by far, with second-highest mortality [2,3]. Anthracyclines have been an integral part of commonly used regimens in adjuvant and non-targeted therapy, decreasing the 10-year risk of breast cancer recurrence and overall mortality [4]. The use of anthracyclines in cancer therapy increases the risk of adverse effects like therapy-related toxicities including cardiomyopathy [5,6]. To improve the safety profile, doxorubicin formulation was optimized by encapsulation in polyethylene glycol (PEG)ylated liposomes that led to the approval of Doxil®. This liposomal drug formulation has markedly reduced the risk of doxorubicin-induced cardiotoxicity [7,8]
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