Delivery of Various Cargos into Cancer Cells and Tissues via Cell-Penetrating Peptides: A Review of the Last Decade

Abstract

Cell-penetrating peptides (CPPs), also known as protein transduction domains, are a class of diverse amino acid sequences with the ability to cross cellular membranes. CPPs can deliver several bioactive cargos, including proteins, peptides, nucleic acids and chemotherapeutics, into cells. Ever since their discovery, synthetic and natural CPPs have been utilized in therapeutics delivery, gene editing and cell imaging in fundamental research and clinical experiments. Over the years, CPPs have gained significant attention due to their low cytotoxicity and high transduction efficacy. In the last decade, multiple investigations demonstrated the potential of CPPs as carriers for the delivery of therapeutics to treat various types of cancer. Besides their remarkable efficacy owing to fast and efficient delivery, a crucial benefit of CPP-based cancer treatments is delivering anticancer agents selectively, rather than mediating toxicities toward normal tissues. To obtain a higher therapeutic index and to improve cell and tissue selectivity, CPP-cargo constructions can also be complexed with other agents such as nanocarriers and liposomes to obtain encouraging outcomes. This review summarizes various types of CPPs conjugated to anticancer cargos. Furthermore, we present a brief history of CPP utilization as delivery systems for anticancer agents in the last decade and evaluate several reports on the applications of CPPs in basic research and preclinical studies.

Advances in Nanoparticles for Effective Delivery of RNA Therapeutics

“…Cell-penetrating peptides (CPPs) are short cationic peptide sequences that mediate the intracellular delivery of numerous biological cargos [62]. It is difficult for large protein complexes, genetic materials, and other molecules to penetrate cellular membranes; however, CPPs, a class of 5-30 residue peptides, can pass through membranes in an energydependent or independent manner [63]. In this regard, peptide-based delivery platforms have been studied as mRNA carriers of genetic materials for intracellular delivery.…”

Designed Multifunctional Peptides for Intracellular Targets

“…One can speculate that DNA-binding and cell-penetrating functions are related and equally ancient for penetratin analogs found in homeobox-like proteins ( Table 1 and Table 2 ). More to the point, membrane activity, cell-penetrating ability, antimicrobial potency, and anticancer activity are also related to the highly cationic and moderately amphipathic structure of the penetratin and its natural or synthetic analogs [ 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ].…”

“…The penetratin (PEN) and other cell-penetrating peptides have a promising potential for drug targeting and oncological pharmacotherapy [ 57 , 58 ]. Combating drug-resistant cancers by targeted delivery of drugs should facilitate the development of effective personalized therapies.…”

Overcoming the cellular barriers and beyond: Recent progress on cell penetrating peptide modified nanomedicine in combating physiological and pathological barriers

“…The combination with CPPs further elevates the delivery efficiency of nanomedicines. Detailed progress has been reviewed elsewhere [ 137 , 138 ], so here we summarize the key advantages of CPP-NPs. Efficiency tumor targeted delivery faces the challenges of (1) targeting efficiency, (2) prolonged retention, (3) deep penetration [139] .…”