FIG. 1.

Dynamic nanocarriers utilizing different cellular microenvironments. Differences in pH (lower in endocytic vesicles and also in special extracellular tumor situations) and redox situation (higher intracellular glutathione [GSH] concentration) can be utilized in the delivery process. Polyplexes stabilized by disulfide formation get internalized by an electrostatic interaction with the cell membrane. Protonation of polymers in the acidifying vesicle triggers destabilizing membrane interactions that are necessary to induce endosomal escape into the cytosol. In the reductive environment of the cytosol, disulfide bonds are cleaved and the cargo is released. Plasmid DNA (pDNA) has to enter the nucleus to get transcribed.