An efficient and low toxic human serum albumin conjugated polyethylenimine nano-sized complex for gene delivery

A novel low cytotoxicity and high efficiency transfection reagent, human serum albumin (HSA)-conjugated polyethylenimine (PEI) was prepared to improve the effect of PEI on gene transfection in this study. Transfecting a cell with DNA is a crucial step for DNA vaccination or gene therapy. PEI, a non-viral vector, is one of the popularly used cationic polymers because of its intensive positive charge that condenses DNA as a nano-sized complex, and attaches on the negative-charged cell membrane, triggering cell endocytosis. In this study, we used a zero-length cross-linkage EDC system to chemically conjugate HSA and PEI, and the size of final synthesized product HSA-conjugated PEI (HSA-PEI) was 14 nm with a positive zeta potential 20.8 mV. We also evaluated the characteristics of HSA-PEI in cells. We chose the A549 cell line as our evaluation model because of its GP-60 receptor. Our results showed that HSA-conjugated PEI was easily applied to form a nano-sized complex with plasmid DNA (pDNA) by simply mixing. The functional ligand, HSA, has a large size, much free PEI (or equivalent free PEI effect) and increases the protection of pDNA by stereo-barring, good condensation effect. HSA-PEI also showed good pDNA transfection enhancement in A549 cell lines, and low toxic characteristics.