Zwitterionic pH/redox nanoparticles based on dextran as drug carriers for enhancing tumor intercellular uptake of doxorubicin

Zwitterionic nanoparticles have excellent serum stability. In this study, pH/redox responsive polymer was synthesized through a modification of dextran using succinic acid, followed by crosslinking with cystamine. The polymer could self-assemble into stable nanoparticles (NPs) in aqueous solution. The NPs carried certain amount of free carboxyl and amino groups on the surface, which endowed the NPs excellent anti-protein adsorption ability. The surface charge was negative at pH 7.4 and was converted to positive at pH 5.0. It was revealed that the NPs showed little non-specific protein adsorption and had excellent serum stability, and the NPs could be internalized in Hela cells rapidly. This result was ascribed to the charge reversible feature of the NPs. Doxorubicin (DOX) was loaded in the NPs for release studies in vitro. The DOX-loaded NPs exhibited obvious pH and reduction sensitivities in response to the environment in tumor cells due to the introduction of carboxyl groups, amino groups and disulfide bonds in the NPs. The NPs were biocompatible, biodegradable, and could be potentially applied as anticancer drug carriers for enhancement of tumor intercellular uptake of doxorubicin. (C) 2015 Elsevier B.V. All rights reserved.