Nowadays, electroporation (EP) represents a promising method for the intracellular delivery of anticancer
drugs. To setting up the process, the EP efficiency is usually evaluated by using cell suspension and adherent cell cultures that are not representative of the in vivo conditions. Indeed, cells are surrounded by
extracellular matrix (ECM) whose composition and physical characteristics are different for each tissue.
So, various three-dimensional (3D) in vitro models, such as spheroids and hydrogel-based cultures, have
been proposed to mimic the tumour microenvironment.
Herein, a 3D breast cancer in vitro model has been proposed. HCC1954 cells were seeded on crosslinked
and lyophilized matrices composed of hyaluronic acid (HA) and ionic complementary self-assembling
peptides (SAPs) already known to provide a fibrous structure mimicking collagen network. Herein,
SAPs were functionalized with laminin derived IKVAV adhesion motif. Cultures were characterized by
spheroids surrounded by ECM produced by cancer cells as demonstrated by collagen1a1 and laminin
B1 transcripts. EP was carried out on both 2D and 3D cultures: a sequence of 8 voltage pulses at 5 kHz
with different amplitude was applied using a plate electrode. Cell sensitivity to EP seemed to be modulated by the presence of ECM and the different cell organization. Indeed, cells cultured on HA-IKVAV were
more sensitive than those treated in 2D and HA cultures, in terms of both cell membrane permeabilization and viability. Collectively, our results suggest that HA-IKVAV cultures may represent an interesting
model for EP studies. Further studies will be needed to elucidate the influence of ECM composition on EP
efficiency