Niosomes-based gene delivery systems for effective transfection of human mesenchymal stem cells

• Published in: Materials Science & Engineering C 2021-09, Vol.128, p.112307-112307, Article 112307
• Main Authors: Carballo-Pedrares, Natalia, Kattar, Axel, Concheiro, Angel, Alvarez-Lorenzo, Carmen, Rey-Rico, Ana
• Format: Article
• Language: English
• Subjects: Cell culture; Cell lines; Cholesterol; Cytotoxicity; Deoxyribonucleic acid; Dispersions; DNA; DOTMA; Evaporation; Galactosidase; Gene transfer; Lipids; Materials science; Mesenchymal stem cells; MSCs; Niosomes; Physicochemical properties; Reagents; Room temperature; Self-assembly; Stability; Steam; Stem cells; Sucrose; System effectiveness; Toxicity; Transfection; β-Galactosidase
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2021.112307

Gene transfer to mesenchymal stem cells (MSCs) has arisen as a powerful approach to increase the therapeutic potential of this effective cell population. Over recent years, niosomes have emerged as self-assembled carriers with promising performance for gene delivery. The aim of our work was to develop effective niosomes-based DNA delivery platforms for targeting MSCs. Niosomes based on 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA; 0, 7 or 15%) as cationic lipid, cholesterol as helper lipid, and polysorbate 60 as non-ionic surfactant, were prepared using a reverse phase evaporation technique. Niosomes dispersions (filtered or not) and their corresponding nioplexes with a lacZ plasmid were characterized in terms of size, charge, protection, and complexation abilities. DOTMA concentration had a large influence on the physicochemical properties of resulting nioplexes. Transfection efficiency and cytotoxic profiles were assessed in two immortalized cell lines of MSCs. Niosomes formulated with 15% DOTMA provided the highest values of β-galactosidase activity, being similar to those achieved with Lipofectamine®, but showed less cytotoxicity. Filtration of niosomes dispersions before adding to the cells resulted in a loss of their biological activities. Storage of niosomes formulations (for 30 days at room temperature) caused minor modification of their physicochemical properties but also attenuated the transfection capability of the nioplexes. Differently, addition of the lysosomotropic agent sucrose into the culture medium during transfection or to the formulation itself improved the transfection performance of non-filtered niosomes. Indeed, steam heat-sterilized niosomes prepared in sucrose medium demonstrated transfection capability. [Display omitted] •Niosomes are suitable gene delivery platforms for targeting immortalized MSCs.•Filtration of niosomes precludes their biological activities.•Storage of niosomes at RT reduces their transfection efficiency.•Addition of sucrose improved gene transfer performance from niosomes.