Abstract

The therapeutic potential of biomacromolecules in treating various diseases is undeniable; however, their application is significantly limited by the inherent barrier function of the cell membrane. Cell-penetrating peptides (CPPs), a class of small peptides comprising fewer than 30 amino acids, have garnered considerable attention due to their exceptional ability to traverse cell membranes. These peptides facilitate the intracellular delivery of various macromolecules, such as proteins, polypeptides, and nucleic acids, thereby overcoming the limitations imposed by the plasma membrane. CPPs exhibit versatile translocation properties, allowing them not only to penetrate cells independently but also to serve as delivery vehicles for therapeutic agents or CPP/cargo complexes. This unique capability has positioned them as promising candidates in the treatment and diagnosis of diseases, including cancer. Their ability to transport biologically active molecules across the plasma membrane enhances the efficacy of therapeutic interventions that would otherwise face significant challenges due to poor cellular uptake. This review explores the classification of CPPs based on their structure and properties, shedding light on the mechanisms that enable their efficient membrane penetration. It also touches into various therapeutic applications of CPPs, emphasizing their potential to revolutionize drug delivery systems. Despite their promise, the clinical utility of CPPs is hindered by challenges such as stability, specificity, and potential cytotoxicity. Addressing these limitations is crucial to unlocking the full potential of CPPs as innovative delivery tools in modern medicine.