Breast cancer cells grown on hyaluronic acid-based scaffolds as 3D in vitro model for electroporation

被引:15
|
作者
Sieni, Elisabetta [1 ]
Bazzolo, Bianca [2 ]
Pieretti, Fabio [3 ]
Zamuner, Annj [3 ]
Tasso, Alessia [2 ]
Dettin, Monica [3 ]
Conconi, Maria Teresa [2 ]
机构
[1] Univ Insubria, Dept Theoret & Appl Sci, Via Dunant 3, I-21100 Varese, Italy
[2] Univ Padua, Dept Pharmaceut & Pharmacol Sci, I-35131 Padua, Italy
[3] Univ Padua, Dept Ind Engn, Via Marzolo 9, I-35131 Padua, Italy
关键词
Electroporation; Breast cancer; Hyaluronic acid; Self-assembling peptides; IKVAV adhesion motif; STANDARD OPERATING PROCEDURES; IRREVERSIBLE ELECTROPORATION; ELECTROCHEMOTHERAPY; ELECTROPERMEABILIZATION; METASTASES; CULTURES; SPHEROIDS; BLEOMYCIN; DELIVERY; MATRIX;
D O I
10.1016/j.bioelechem.2020.107626
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2020 Elsevier B.V. All rights reserved.
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页数:11
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