Intracellular Protein Delivery Systems Formed by Noncovalent Bonding Interactions between Amphipathic Peptide Carriers and Protein Cargos.

Successful molecular therapy using protein-based therapeutic agents for intracellular targets depends on the development of efficient and safe protein delivery systems that are able to overcome the problem of poor permeability of cell membrane to proteins. Here, we summarize recent studies elucidating how one particular class of peptide-based carriers, amphipathic peptide, has been designed and utilized for intracellular protein delivery in a simple yet effective manner. The unique feature of these delivery systems lies in the noncovalent binding of amphipathic peptides to protein cargos, mainly through hydrophobic interactions. At least five different types of amphipathic peptides have been developed and demonstrated to be able to deliver various biologically active proteins into a variety of cell types without the use of chemical conjugation. In view of their efficiency and presumably low toxicity, we anticipate that amphipathic peptides will continue to be developed as powerful carriers for intracellular delivery of protein therapeutics.