Surface-Potential-Regulated Transmembrane and Cytotoxicity of Chitosan/Gold Hybrid Nanospheres

Chitosan−gold hybrid nanospheres with varying surface zeta potentials were designed as a model system to investigate cell internalization. Gold nanoparticle was selected as optical marker to facilitate the visualization of the hybrid polymeric nanosphere internalization course and the localization in the cell by dark-field optical microscopy and transmission electron microscopy. It is found that surface potential has significant biological implications in the transmembrane efficiency, intracellular fate, and cytotoxicity of the hybrid nanospheres. Compared to those with lower surface potential, the spheres with higher surface potential show a faster cell uptake and enhance the nucleus targeting. However, too high a surface potential may destabilize the cell membrane and induce cell damage as well as cytotoxicity. These finding can help us to design suitable drug or gene nanocarriers with low cytotoxicity and high delivering ability.