Guanidinylated bioresponsive poly(amido amine)s designed for intranuclear gene delivery

Abstract

Guanidinylated poly(amido amine)s with multiple disulfide linkages (Gua-SS-PAAs) were designed and constructed as nonviral gene carriers. The main chains of these novel carriers were synthesized based on monomers containing guanidino groups (guanidine hydrochloride and chlorhexidine), which could avoid complicated side-chain-modification reactions while introducing the guanidino groups. The synthesized Gua-SS-PAAs polymers were characterized by ¹H nuclear magnetic resonance, molecular weight, and polydispersity. Furthermore, Gua-SS-PAAs polymers were complexed with pDNA, and the properties of the complexes were determined, including entrapment efficiency, particle size, ζ-potential, atomic force microscopy images, stability, DNA complexation ability, reduction sensitivity, cytotoxicity, and transfection efficiency. The new Gua-SS-PAAs carriers exhibited higher transfection efficiency and lower cytotoxicity compared with two widely used gene delivery carriers, polyethylenimine and lipofectamine 2000. Furthermore, the relationship between the side-chain structure and morphological/biological properties was extrapolated, and the results showed that guanidine in the side chain aids in the improvement of transfection efficiency. In addition, the introduction of guanidino group might confer the new carriers with nuclear localization function compared to carriers without it.

Keywords:

• gene carrier
• transfection efficiency
• cytotoxicity
• nuclear localization
• guanidine

Acknowledgments

This work was supported in whole or in part by the Center for Biological Imaging, Institute of Biophysics, Chinese Academy of Sciences, and the School of Pharmacy, China Medical University. The authors are grateful to the Natural Science Foundation Committee of China for financial support (no 81373335).

Disclosure

The authors report no conflicts of interest in this work.