The Utilization of Cell-Penetrating Peptides in the Intracellular Delivery of Viral Nanoparticles

Abstract

Viral particles (VPs) have evolved so as to efficiently enter target cells and to deliver their genetic material. The current state of knowledge allows us to use VPs in the field of biomedicine as nanoparticles that are safe, easy to manipulate, inherently biocompatible, biodegradable, and capable of transporting various cargoes into specific cells. Despite the fact that these virus-based nanoparticles constitute the most common vectors used in clinical practice, the need remains for further improvement in this area. The aim of this review is to discuss the potential for enhancing the efficiency and versatility of VPs via their functionalization with cell-penetrating peptides (CPPs), short peptides that are able to translocate across cellular membranes and to transport various substances with them. The review provides and describes various examples of and means of exploitation of CPPs in order to enhance the delivery of VPs into permissive cells and/or to allow them to enter a broad range of cell types. Moreover, it is possible that CPPs are capable of changing the immunogenic properties of VPs, which could lead to an improvement in their clinical application. The review also discusses strategies aimed at the modification of VPs by CPPs so as to create a useful cargo delivery tool.

Self-Assembly of Organic Nanomaterials and Biomaterials: The Bottom-Up Approach for Functional Nanostructures Formation and Advanced Applications

“…A variety of CPPs has been synthesized and utilized to translocate a variety of active compounds, such nucleic acids, proteins, nanoparticles and imaging and contrast agents in preclinical (and clinical) investigations [141]. Recently, CPPs were utilized in the enhancement of the intracellular delivery efficiency of viral nanoparticles, which caused a reduction of the consumption of materials, thus allowing a minimization of virus nanoparticles cytotoxicity, and reducing the risks in their potential clinical application [142].…”

Materials promoting viral gene delivery

“…302 Their ability to transport variable cargo across cellular membranes has made CPPs a facile tool for the delivery of DNA and RNA, liposomes, nanoparticles, proteins, and drugs as reviewed elsewhere 303,304 and of viral nanoparticles for efficient transduction as comprehensively reviewed. 305,306 In this segment, we highlight the most important developments in CPPs for facilitating transport of VP into target cells.…”

Oncogenic Properties of the EBV ZEBRA Protein

“…CPDs are short sequences with a composition that enables them (and the adjacent protein) to penetrate cells either via endocytotic entry followed by endosomal escape, or by directly penetrating the cell membrane. Their composition is usually either cationic (with a high number of positively charged residues) or amphipathic (with hydrophilic and hydrophobic regions of residues) [46]. ZEBRA CPD is rich in positively charged residues (seven lysines and seven arginines), mostly within DBD (basic region) ( Figure S1A in blue), whereas hydrophobic amino acids (one valine, five alanines, seven leucines) of CPD are mostly within DD (leucine zipper) (Figure S1B in red) [36].…”