This theme issue, edited by Hamm-Alvarez and Okamoto (University of Southern California), brings together a collection of articles authored by experts working in the areas of pharmaceutical and/or cell biological aspects of endocytosis. The text provides a unique insight into the growing understanding of the cell’s trafficking machinery and how this intricate network of intracellular highways can be best exploited to improve drug delivery. The collected reviews describe mechanisms of cellular uptake and trafficking of proteins and viruses using transferrin, riboflavin (Rf), adenovirus and adenovirus capsid proteins, and herpes simplex virus as examples. Also described are the sorting motifs that influence receptor and vesicle trafficking. Motor proteins and cytoskeleton play an important role in the regulation of vesicle movement and this topic is also reviewed. Dysfunction in trafficking and endosomal/lysosomal systems causes many diseases and contributes to the ageing process. This topic is discussed with particular emphasis on aspects of neuronal degeneration during ageing.

Since the pioneering work of De Duve et al.[1] in the 1970s, it has been recognised that the promise of macromolecular therapeutics and drug delivery systems can only be realised with a thorough understanding of the biochemistry and cell biology of endocytosis. There are an increasing number of macromolecular drugs (proteins, oligonucleotides, and synthetic polymers), macromolecular conjugates (of polymers, proteins, and antibodies), and nanosized drug carriers (liposomes, nanoparticles, and viral vectors) in research and development, so the need to comprehend endocytic pathways has never been more apparent. Although the last decade has seen the first polymer–protein conjugates and liposomal formulations enter routine clinical use [1–4], rapid progress in genomics and proteomics research is discovering many new and interesting therapeutic targets. Effective delivery systems able promote the targeted delivery of peptides, proteins, and oligonucleotides to specific intracellular compartments are desperately required.