Nanocarriers with tunable surface properties to unblock bottlenecks in systemic drug and gene delivery

Nanocarriers with fixed surface properties, such as a PEGylated, cationized and bioconjugated surface, play conflicting roles at different stages of the extracellular and intracellular delivery of drugs and genes in vivo. One of these conflicts is the well-known “PEG dilemma” that PEGylated nanocarriers achieve a prolonged circulation time but strongly inhibit cellular uptake and endosomal escape. Cationized and bioconjugated ligands have been successfully utilized to enhance intracellular delivery, but they are more easily cleared from blood circulation. Thereby, the tunable surfaces of nanocarriers surmounting both extracellular and intracellular barriers open up the possibility of high-efficient delivery in vivo.216