Gateways for the intracellular access of nanocarriers: a review of receptor-mediated endocytosis mechanisms and of strategies in receptor targeting.

IMPORTANCE OF THE FIELD: The last 10 years have seen a dramatic growth in understanding and controlling how complex, drug-loaded (nano)structures, as well as pathogens, or biopharmaceuticals can gather access to the cytoplasm, which is a key step to increasing the effectiveness of their action. AREAS COVERED IN THIS REVIEW: The review offers an updated overview of the current knowledge of endocytic processes; furthermore, the cell surface receptors most commonly used in drug delivery are here discussed on the basis of their reported internalization mechanisms, with examples of their use as nanocarrier targets taken from the most recent scientific literature. WHAT THE READER WILL GAIN: Knowledge of molecular biology details is increasingly necessary for a rational design of drug delivery systems. Here, the aim is to provide the reader with an attempt to link a mechanistic knowledge of endocytic mechanisms with the identification of appropriate targets (internalization receptors) for nanocarriers. TAKE HOME MESSAGE: Much advance is still needed to create a complete and coherent biological picture of endocytosis, but current knowledge already allows individuation of a good number of targetable groups for a predetermined intracellular fate of nanocarriers.