Chitosan-based core–shell structured particles for in vivo sustainable gene transfection

A core–shell structured chitosan (CS)-based gene vector with a sustainable gene transfection effect was designed and successfully prepared in this study. The pEGFP was first combined with the thiolated and N-alkylated chitosan (TACS). Then, hydroxybutyl chitosan grafted with poly(ethylene glycol) (EG–HBC) was coated on the pEGFP-loaded TACS particles. The prepared pEGFP-loaded TACS@EG–HBC particles have a size of about 200 nm and little cytotoxicity. The in vitro and in vivo gene transfection experiments indicate that the pEGFP-loaded TACS@EG–HBC particles possess a better sustainable gene transfection capacity and a high transfection efficiency, which should be attributed to the biodegradation of the CS-based shell, the thiolation and N-alkylation modification on CS cores, and the grafted PEG chains with better biocompatibility. The in vivo gene expression of the loaded pEGFP can persist up to 60 days. This novel gene vector has a theoretical and practical significance for gene therapy with sustained transfection effect.