Abstract
Tumor electroporation (EP) refers to the permeabilization of the cell membrane by means of short electric pulses thus allowing the potentiation of chemotherapeutic drugs. Standard plate adhesion 2D cell cultures can simulate the in vivo environment only partially due to lack of cell–cell interaction and extracellular matrix (ECM). In this study, we assessed a novel 3D scaffold for cell cultures based on hyaluronic acid and ionic-complementary self-assembling peptides (SAPs), by studying the growth patterns of two different breast carcinoma cell lines (HCC1569 and MDA-MB231). This 3D scaffold modulates cell shape and induces extracellular matrix deposit around cells. In the MDA-MB 231 cell line, it allows three-dimensional growth of structures known as spheroids, while in HCC1569 it achieves a cell organization similar to that observed in vivo. Interestingly, we were able to visualize the electroporation effect on the cells seeded in the new scaffold by means of standard propidium iodide assay and fluorescence microscopy. Thanks to the presence of cell–cell and cell–ECM interactions, the new 3D scaffold may represent a more reliable support for EP studies than 2D cancer cell cultures and may be used to test new EP-delivered drugs and novel EP protocols.
Highlights
Cell membrane electroporation (EP) is a physical phenomenon exploited in different emerging cancer treatments such as electrochemotherapy (ECT) and irreversible EP (IRE)
This paper presents a first evaluation of the use of a new 3D scaffold for cell cultures to be used in electroporation experiments
In this work we present a new 3D scaffold able to modulate cell shape and to induce an extracellular matrix deposit around cells, making this model more useful than 2D cancer cell cultures to test drug delivery protocols by electroporation
Summary
Cell membrane electroporation (EP) is a physical phenomenon exploited in different emerging cancer treatments such as electrochemotherapy (ECT) and irreversible EP (IRE). Through the administration of properly tuned electric pulses, EP leads to reversible (as in ECT) or irreversible (as in IRE) cell membrane permeabilization. While in ECT, EP increases the uptake and activity of concomitant chemotherapy, in IRE it is applied as a standalone therapy which provokes irrecoverable cell imbalance [1,2,3,4,5,6]. ECT has been first standardized in 2006 and the currently adopted protocols in clinical practice include pre-determined standardized parameters [1,7]. The electroporation protocol for skin tumors is standardized in terms of voltage and the number of pulses in the framework of the European Standard Operating Procedure on Electrochemotherapy (ESOPE). The voltage amplitude is related to the electrode geometry and in particular to the distance between electrode needles
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