Cellular Uptake Mechanisms of Arginine‐Rich Cell‐Penetrating Peptides

Arginine-rich cell-penetrating peptides (CPPs), such as human immunodeficiency virus type 1(HIV-1) Tat peptide [Tat (48–60)], oligoarginines, and other functionalized peptides, have been developed and used as carriers to obtain efficient intracellular delivery of bioactive and therapeutic molecules. In this chapter, the latest findings regarding our understanding of the cellular uptake mechanisms of arginine-rich CPPs are summarized from the viewpoint of chemical biology. This includes endocytosis and membrane penetration, membrane curvature, toxicity, and the importance of controlling the intracellular location of the peptides following uptake to obtain the desired biological activity of the cargo molecules delivered by arginine-rich CPPs.