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.