Nonviral Gene Delivery Systems Based on Cationic Benzimidazolium Surfactants and Fusogenic Lipids

The incorporation of biocompatible cationic surfactants into non-viral gene nanocarriers is an attractive approach that has recently gained increasing interest. In this work, cationic liposomes based on a benzimidazolium surfactant with a hexadecyl tail (BI-16) and auxiliary lipids (DOTAP, DOPE, and Chol) were prepared for evaluation as potential carriers of genetic material (model oligonucleotide). An interdisciplinary approach was used to study the systems: (1) physicochemical evaluation of the obtained liposomes and lipoplexes (depending on the charge ratio of the N/P components), including the study of size, zeta potential, polydispersity index, and stability; (2) biological studies, including experiments to evaluate the cytotoxic effects of the systems, their ability to be internalized by cancer cells (depending on the charge ratio of the N/P components), and a study of hemolytic and hemagglutination activities. The results showed that the resulting nanocarriers are capable of effectively binding the oligonucleotide into compact complexes with an average size of 60 to 150 nm. The lipoplexes exhibited a spherical morphology and were effectively internalized by M-HeLa, A549, and HuTu80 cancer cells. A key influence of the charge ratio of the N/P components on the ability of the systems to cause hemagglutination and to be internalized by cancer cells was established.