Crossing biological barriers is often required for drug delivery. Cell-penetrating peptides (CPPs) are short strands of amino acids that have been widely used as a delivery vehicle to overcome barriers for various applications. This review aims to emphasize the role of CPPs as permeation enhancers for targeted drug delivery applications. We also discuss the prospect of clinical translation of CPP-functionalized drug delivery systems in oncology. This may help facilitate the development of new types of CPPs for preventing or treating cancer.

Cell-Penetrating Peptides (CPPs) are short peptides consisting of <30 amino acids. Their ability to translocate through the cell membrane while carrying large cargo biomolecules has been the topic of pre-clinical and clinical trials. The ability to deliver cargo complexes through membranes yields potential for therapeutics and diagnostics for diseases such as cancer. Upon cellular entry, some CPPs have the ability to target specific organelles. CPP-based intracellular targeting strategies hold tremendous potential as they can improve efficacy and reduce toxicities and side effects. Further, recent clinical trials show a significant potential for future CPP-based cancer treatment. In this review, we summarize recent advances in CPPs based on systematic searches in PubMed, Embase, Web of Science, and Scopus databases until 30 September 2022. We highlight targeted delivery and explore the potential uses for CPPs as diagnostics, drug delivery, and intrinsic anti-cancer agents.