Efficient gene delivery using a novel core‐shell nanoparticle and HMGB1 system

Abstract

We have recently developed a highly efficient gene delivery system of amphiphilic core-shell nanoparticle composed of poly(methyl methyacrylate) core and branched poly(ethylenimine) shell for transfection of DNA into mammalian cells. In order to enhance the efficiency and to provide the nuclear targeting capability, we have tried the inclusion of a nuclear protein HMGB1 in our system. The high mobility group protein HMGB1 itself has been shown in various earlier studies to be able to enhance the transfection efficiency when used with both naked DNA and liposomes. In our present study, HMGB1 protein was added together with the DNA and the nanoparticles to form the gene delivery complexes. Formation of the complexes was demonstrated using agarose gel retardation assay and the DNA with HMGB1 still bound can be released from the complexes with the use of polyaspartic acids. When used in transfection into mammalian cells, transfection efficiency of the HMGB1-nanoparticle-DNA complexes was found to be significantly higher than that without HMGB1. We believe that this system with the inclusion of HMGB1 has the potential to be developed into a viable and efficient non-viral gene carrier for use in vivo. YSS is supported by a PolyU studentship, KLDL is supported by a PolyU internal research grant and PL is supported by a CERG grant.