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Cationic antimicrobial peptides (AMPs) have long been considered for the development of novel therapeutics due to their potent antimicrobial activity and biocompatibility. However, it is becoming increasingly evident that these peptides are endowed with a number of additional properties, particularly for their ability to cross biological membranes. In this regard, cell-penetrating peptides (CPPs) have the unique property of being able to translocate across the plasma membrane, having the potential to facilitate delivery of therapeutic payloads to cells. Based on this feature, the development of CPP-based therapeutic vectors is emerging as a promising area of research. In this study, we used a panel of antimicrobial peptides to identify cationic peptides that possess the capacity to cross cell membranes in a highly efficient manner. One of these peptides, which we name “CECPP,” was then used in conjunction with a tumor-targeting antibody, anti-CCR4, to create an efficacious bi-functional transmembrane protein (TM) delivery vehicle that possesses the ability to penetrate tumor cells and target cancer stem cells.
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