Cyclic Cell-Penetrating Peptides as Efficient Intracellular Drug Delivery Tools

Abstract

Cyclic cell-penetrating peptides are relatively a newer class of peptides that have a huge potential for the intracellular delivery of therapeutic agents aimed at treating challenging ailments like multidrug-resistant bacterial diseases, cancer, and HIV infection. Cell-penetrating peptides (CPPs) have been extensively explored as intracellular delivery vehicles; however, they have some inherent limitations like poor stability, endosomal entrapment, toxicity, and suboptimal cell penetration. Owing to their favorable properties that avoid these limitations, cyclic CPPs can provide a good alternative to linear CPPs. Several Reviews have been published in the past decade that cover CPPs and cyclic peptides independently. To the best of our knowledge, this is one of the first Reviews that covers cyclic CPPs comprehensively in the light of studies published so far. In this Review, we have detailed examples of cyclic CPPs, their structures, and cyclization strategies followed by a detailed account of their advantages over their linear counterparts. A hot area in cyclic CPPs is the exploration of cell-penetration mechanisms; this Review highlights this topic in detail. Finally, we will review the applications of cyclic CPPs, followed by conclusions and future prospects.

Anticancer peptide: Physicochemical property, functional aspect and trend in clinical application (Review)

“…Drug concentration and cell and tissue barriers are an obstacle for therapeutic efficacy. Medical application for drug delivery requires biologically active conjugates (cargoes) and/or binding peptides ('guiding missile') to reach specific intracellular targets ( 102 - 104 ). Minimal amino acid sequences of various cell-penetrating peptides, typically comprising 5-30 amino acid residues, especially cationic residues, can pass through tissue and cell membranes using energy-dependent or -independent mechanisms without the interaction of specific receptors ( 36 ).…”

Cyclic Peptide-Gadolinium Nanoparticles for Enhanced Intracellular Delivery

“…A peptide-based drug delivery system is one of the extensively used tools to overcome major obstacles in permeation into cells. In recent years, synthetically engineered cyclic peptides have been utilized as drug delivery systems for transporting various types of molecular cargos such as anticancer drugs and siRNAs [16]. The cyclic nature of peptides has been discovered to be critically important to enhance their intracellular transporting efficiency [17][18][19].…”

A gold mine for drug discovery: Strategies to develop cyclic peptides into therapies

“…Moreover, cyclic CPPs also exhibit efficient endosomal escape and strong ability of conjugation with therapeutic and imaging agents . Thus, cyclic CPPs have been widely used as powerful intracellular drug delivery tools, aiming for the therapy of challenging diseases like cancer, multidrug‐resistant bacteria and HIV infections …”