Accordingly, as this study examined cationic niosomes containing Span 20 and spermine-cationic lipids, the high gene transfection observed in this work might be due to the ability of these cationic lipids to become protonated at intralysosomal acidic pH, which could lead to endosomal membrane destabilization and the cytosolic release of the carried DNA, finally, gene transcription and translation. Lysosomotropic detergents such as lipophilic amine can be protonated at intralysosomal acidic pH levels, resulted in enhanced endosomal escape (Liang and Hughes, 1998). Therefore, the role of cationic niosomes in gene delivery and the mechanism of cellular uptake and intracellular process will be further investigated.