Developing New Self-Assembled Cationic Amino Liposomes for Stem Cell Transfection

Cationic liposomes as good DNA or siRNA delivery carriers have been widely reported for many different cells. However, for hard-to-transfect stem cells, most of cationic liposomes showed low transfection efficiency and high cytotoxicity, which hampered their applications in clinical and industry. Here, to conquer this limitation, we design and parallelly synthesize a library of new cationic amino liposomes via a facile one-step method based on Michael addition. A library of 83 structurally diverse cationic amino liposomes has been successfully constructed, which is made from 6 different amines, 9 different linkers and 2 different mercaptan hydrophobic tails. Compared with the commercial reagent named Lipofectamine 2000 in terms of plasmid transfection efficiency in HEK293T cells and siRNA transfection efficiency in U87Luc-GFP cells, several cationic amino liposomes that we designed showed comparable or even better transfection efficiency in both siRNA and plasmid delivery. The structure-activity relationship study shows that both the length of the alkyl amines and surface charge play important roles in the transfection efficiency in stem cells. Among this batch of liposome library, A2cT2 showed best transfection efficiency in hard-to-transfect stem cells. It is envisioned that the cationic amine liposomes could be extended to other hard-to-transfer cells and with higher cellular transfection efficiency, which is of high importance in clinical applications.