Bilirubin-based ROS responsive hydrophobicity/hydrophilicity switchable hybrid vector for gene delivery

The insufficient endocytosis and the low expression efficiency of the transfected gene in the lesion are still the main challenge for gene therapy. Herein, a novel bilirubin (BR)-based ROS responsive hydrophobicity/hydrophilicity switchable BR-grafted polylysine (PLL)/DNA nanosystem is designed by condensing indocyanine green (ICG) onto the surface of vector through electrostatic interaction between ICG and PLL, which can prolong the blood circulation time of nanocomplexes, and thus enhance the gene transfection efficiency due to the favorable solubility exchange of BR from hydrophobicity to hydrophilicity under ROS stimulus and the increased roughness of coated ICG. The in vitro and in vivo results demonstrate that the BR-based ROS responsive hydrophobicity/hydrophilicity switchable nanosystem with a rough surface can enhance the endocytosis of the nanoparticles, and consequently facilitate the gene therapy in an inflammatory environment. Our delicate design concept can expand to develop an anti-inflammation nanocarrier for efficient gene therapy in an inflammatory setting.