Polyethyleneimine/DNA/Modified Bovine Serum Albumin Ternary Complex, A Biocompatible And Effective Gene Delivery System

Gene therapy has been proved to be an attractive way to treat various intractablediseases. To achieve successful gene therapy, safe and efficient gene delivery systemis required. Nonviral gene delivery systems based on cationic polymers (polycations)have attracted much attention due to their potential advantages such as flexiblemanufacturing and facile modification. As the golden standard of nonviral genedelivery, polyethyleneimine (PEI) has been widely used in gene therapy. But thefurther application of PEI is still limited by its high cytotoxicity which is caused byionic interaction between the excess positive charges of PEI/nucleic acid complexes(polyplexes) and the negative cell membrane. Various methods have been applied toreduce the cytotoxicity of PEI polyplexes by shielding the positive surface charges.Unfortunately, those shielding strategies often reduced transfection efficiency of PEIpolyplexes.In this study, PEI/DNA/modified bovine serum albumin (mBSA) ternarycomplexes were prepared, which have excellent biocompatibility and higher genetransfection efficiency compared with PEI/DNA binary complexes. The molecularweight of mBSA was confirmed by MALDI-TOF. PEI/DNA/mBSA ternarycomplexes were formed by electrostatic interaction in physiological pH. Thedissociation of ternary complexes in pH5.5was confirmed by DLS and TEM. Cellviabilities assayed by MTT and gene transfection assay demonstrated that mBSAreduced the cytotoxicity of the binary complexes (PEI/DNA) while increased theirgene transfection efficiency at the same time. The ternary complexes were also provedto be resistive to serum albumin. The experimental results of cell internalization andintracellular distribution of ternary complexes (PEI/DNA/mBSA) confirmed that theimprovement of transfection efficiency originated from the enhancement ofendosomal escape of PEI polyplexes. Therefore, compare with PEI/DNA binarycomplexes, PEI/DNA/mBSA ternary complexes has been proven to have higher genetransfection efficiency and more biocompatible.