Taming Cell Penetrating Peptides: Never Too Old To Teach Old Dogs New Tricks

Cell penetrating peptides (CPPs) have received substantial attention due to their intrinsic property to cross plasma membranes or even as helpers to facilitate the cellular entry of drug molecules, macromolecules, and nanoparticles. Although CPPs and CPP-like peptides provided versatile platforms for drug delivery, their nonselectivity or lack of delivery efficiency is stirring up debates as to the tactics for the optimizing the CPPs themselves. The good news is that, as spurred by the recent progress in the understanding of tumor microenvironment as well as biochemistry and material sciences, we have made attempts in working on perfecting or even "taming" CPPs and CPP-functionalized drug vectors for tumor delivery, and some of them afforded gratifying results. Due to the fact that these peptides are mainly short peptides made up of amino acids (5-30 amino acids), the addition, modification, or replacement of amino acids might lead to surprisingly improved performance. Several novel environment-responsive CPPs or CPP-like peptides have also been discovered. In this review we will discuss the measures taken to harness the power of CPPs and the discovery of environment-responsive peptides with CPP properties.