Cell-penetrating peptides in nanodelivery of nucleic acids and drugs

The hydrophobic nature of cell membranes is one of the major obstacles in the therapeutic delivery of nucleic acids and drug-loaded nanoparticles. Cell-penetrating peptides (CPPs) have the ability to pass biological membranes and enter cells. Due to this intrinsic property, CPPs are employed as vectors for intracellular delivery of nucleic acids and nanoparticles. In this chapter, we first briefly describe the classification and uptake mechanisms of CPPs. Then, we describe the recent therapeutic applications of CPP-modified nanoparticles as drug carriers. In this context, we give an overview of covalent and noncovalent conjugation of CPPs. The second part involves the use of CPPs in nonviral delivery of nucleic acids. Although viral vectors are highly efficient systems for introducing genes, the safety issues with viral systems need to be considered. Nanoparticle-based nonviral vectors provide an attractive alternative, but their gene transfection efficiency is very low. Therefore, novel design strategies are needed to enhance the efficiency. We summarize the use of CPPs in enhancing gene transfer efficiency of nonviral vectors. Besides the clinical potential of currently known CPPs, we also discuss the limitations and the need for designing novel CPPs. © 2018 Elsevier Inc. All rights reserved.