Endosome-disruptive peptides for improving cytosolic delivery of bioactive macromolecules.

Along with recent advances in therapeutic technologies based on biomacromolecules, including genes, oligonucleotides, and proteins, the development of technologies for improving the efficiency of the delivery of these therapeutic molecules into cells, more specifically into the cytosol and nucleus, is significantly required. Cell membranes are major impediments to the delivery of therapeutic macromolecules into cells. These macromolecules are usually taken up by the cells via endocytosis, and their translocation from endosomes to the cytosol is a critical step to determine their therapeutic effects. Many viruses and bacterial toxins use endocytic pathways to invade the host mammalian cells, and some of these pathogens have the ability to facilitate their endosomal escape into the cytosol by pH-induced alteration in their component proteins that leads to the disruption of the endosomal membranes and the eventual membrane fusions. To simulating these functions, endosome-disruptive peptides have been used for the intracellular delivery of biomacromolecules to accelerate their endosomal escape by sensing the endosomal acidification. In this review, current approaches for the intracellular delivery using these endosome-disruptive peptides are surveyed.