Surface charge-reversible polyelectrolyte complex nanoparticles for hepatoma-targeting delivery of doxorubicin

Polymeric nanoparticles are greatly advancing the field of nanomedicine due to their ability for targeted and controlled drug release. Here, monodisperse pH-responsive surface charge-reversible and hepatoma-targeting polyelectrolyte complex nanoparticles (GC/HA NPs) near 80 nm were prepared via the ionotropic gelification by simple and mild co-precipitation of galactosylated chitosan (GC) and hyaluronate (HA). Their surface charges could transfer from negative in neutral or basic media to positive in acidic media, indicating their potential application for delivering anti-tumor drugs in response to the extracellular pH of the tumor environment. The unique "electrostatic sponge" structure enhanced their drug-loading capacity and encapsulation efficiency towards the anti-cancer agent doxorubicin (DOX), as well as the pH-triggered controlled release. MTT assays and fluorescence microscopy analysis revealed that the DOX-loaded GC/HA NPs possessed the hepatoma-targeting capacity with favorable biocompatibility. These features make them advanced anti-cancer drug nanocarriers for intelligent drug delivery systems.