Endocytosis is a fundamental process in which eukaryotic cells internalise molecules and macromolecules via deformation of the membrane and generation of membrane-bound carriers. Functional aspects are not only limited to uptake of nutrients, but also play a primary role in evolutionary conserved processes such as the regulation of plasma membrane protein activity (i.e. signal-transducing receptors, small-molecule transporters and ion channels), cell motility and mitosis. The macromolecular nature of the material transported by endocytosis makes this route one of the most important targets for nanomedicine. Indeed, many nanoparticle formulations have been customised to enter cells through endocytosis and deliver the cargo within the cell. In this critical review, we present an overview of the biology of endocytosis and discuss its implications in cell internalisation of nanoparticles. We discuss how nanoparticle size, shape and surface chemistry can control this process effectively. Finally, we discuss different drug delivery strategies on how to evade lysosomal degradation to promote effective release of the cargo (376 references).
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