Self-assembled CaP-based hybrid nanoparticles to enhance gene transfection efficiency in vitro and in vivo: beneficial utilization of PEGylated bisphosphate and nucleus locating signal

Abstract

Calcium phosphate (CaP) nanoparticles have been considered as a non-viral gene delivery vehicle, but the weakness of inconsistent and low transfection efficiencies is limited to its progress. In order to overcome these weaknesses and to improve the consistency and efficiency of CaP nanoparticles, a pH-sensitive core–shell system mPEG-Pam/CaP/HMGB1/pDNA hybrid nanoparticle was prepared. The PEGylated pamidronate (mPEG-Pam) segment forms a hydrophilic outer shell for enhancing the stability of nanoparticles and HMGB1 was used as a nucleus locating signal (NLS) to improve the efficiency of nucleus importation and gene expression. The formed hybrid nanoparticles presented small particle size and desired serum stability with the assistance of the mPEG-Pam outer layer. The results of RFP fluorescence intensity analysis in HepG2 cells showed that the hybrid nanoparticles exhibited higher transfection capability with the help of HMGB1 as compared to that of the nanoparticles without the HMGB1. More importantly, after intravenous injection in tumor-bearing S180 nude mice, the hybrid nanoparticles specifically accumulated into the tumor regions by EPR effect, leading to efficient gene expression and anti-tumor effects in vivo. We concluded that the hybrid nanoparticles possessed potential as a safe and effective pDNA delivery system.