Challenge to overcome current limitations of cell-penetrating peptides

The penetration of biological membranes is a prime obstacle for the delivery of pharmaceutical drugs. Cell-penetrating peptide (CPP) is an efficient vehicle that can deliver various cargos across the biological membranes. Since the discovery, CPPs have been rigorously studied to unveil the underlying penetrating mechanism as well as to exploit CPPs for various biomedical applications. This review will focus on the various strategies to overcome current limitations regarding stability, selectivity, and efficacy of CPPs. • Cell-penetrating peptides effectively deliver various cargo molecules across the cell membranes • Cargo molecules are covalently or non-covalently loaded on the cell-penetrating peptides • Clinical application of cell-penetrating peptides is hampered by limited stability, selectivity and efficacy • Various chemical and biological strategies are developed to overcome the limitations of cell-penetrating peptides