Modified bovine serum albumin as an effective charge-reversal platform for simultaneously improving the transfection...

The charge-reversal strategy is usually employed in gene delivery to facilitate the endosomal escape of gene carriers and the release of the payload into cytoplasm. However, most of the charge-reversal materials are far from perfect biocompatible materials due to the cytotoxicity of themselves or their hydrolyzed products. In this study, an excellent charge-reversal material named modified bovine serum albumin (mBSA) was prepared. The charge reversal of biocompatible mBSA is a physical process and can instantly occur, which was confirmed by zeta potential, size detection and morphological studies. The introduction of mBSA can not only reduce the zeta potential of binary complexes (pDNA-PEI) but also increase the nuclease resistance ability of the pDNA-PEI binary complexes. In addition, cell viabilities tested by MTT assay and gene transfection assay demonstrated that mBSA can reduce the cytotoxicity of pDNA-PEI polyplexes and improve their gene transfection efficiency (serum free and 10% FBS medium) both in 293T and HepG2 cells at the same time. The experimental results of cell internalization and intracellular distribution of pDNA-PEI-mBSA ternary complexes confirmed that the improvement of transfection efficiency originated from the enhancement of endosomal escape of polyplexes. Therefore, mBSA has been proven to be a perfect charge-reversal platform to simultaneously improve the transfection efficiency and biocompatibility of polyplexes.