Effect of hydrophobic tails of plier-like cationic lipids on nucleic acid delivery and intracellular trafficking

In this study, the plier-like cationic niosomes (PCNs) containing PCL (A, B, and C) were evaluated their performance to deliver pDNA and siRNA to HeLa cells. Among the PCNs, PCN-B with saturated asymmetric hydrocarbon tails (C18 and C12) provided the highest efficiency for pDNA and siRNA delivery. Furthermore, the results revealed that the structure of the cationic lipids affected the internalization pathway and the intracellular trafficking. PCL-B and PCL-C with asymmetric tails preferred clathrin- and caveolae-mediated endocytosis as the predominant internalization pathways and were also involved in the polymerization process for transfection. However, PCL-A with symmetry hydrocarbon tails (C12) was predominantly taken up via macropinocytosis. All PCNs were able to escape from endosomal–lysosomal systems through facilitation of acidification. Results obtained from the cytotoxicity test revealed that the PCNs were safe in vitro. Therefore, PCNs provide a great prospect as an alternative effective gene delivery system.Graphical abstract
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research