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.

如今，电穿孔（EP）代表了一种有望在细胞内递送抗癌药物的方法。为了建立该过程，通常通过使用不代表体内条件的细胞悬浮液和贴壁细胞培养物来评估EP效率。实际上，细胞被细胞外基质（ECM）包围，细胞外基质的组成和物理特性对于每个组织而言都是不同的。因此，已经提出了各种三维（3D）体外模型，例如球体和基于水凝胶的培养物，以模拟肿瘤的微环境。

这里是体外的3D乳腺癌已经提出了模型。将HCC1954细胞接种在由透明质酸（HA）和离子互补自组装肽（SAPs）组成的交联冻干基质上，已知该基质可提供模仿胶原网络的纤维结构。在本文中，SAP用层粘连蛋白衍生的IKVAV粘附基序功能化。如胶原1a1和层粘连蛋白B1转录本所证明，培养物的特征是由癌细胞产生的被ECM包围的球状体。对2D和3D培养均进行EP：使用平板电极以5 kHz的振幅施加8个电压脉冲序列，振幅不同。细胞对EP的敏感性似乎受到ECM的存在和不同细胞组织的调节。实际上，在HA-IKVAV上培养的细胞比在2D和HA培养中处理的细胞更敏感，就细胞膜通透性和生存力而言。总的来说，我们的结果表明，HA-IKVAV培养可能代表了EP研究的一个有趣模型。需要进一步的研究来阐明ECM组成对EP效率的影响。