Table 7.

Sample cell-penetrating peptides and their applications in targeted and untargeted peptide delivery.

Name/Description	Sequence	Category	Outcomes of interest	Ref.
TAT	CGRKKRRQRRRPPQC	Protein derived CPP from HIV-1	Able to deliver peptides, proteins, nanoparticles and oligonucleotides intracellularly	[222]
Penetratin	RQIKIWFQNRRMKWKK	Protein derived CPP from Drosophila antennapedia domain	Able to deliver a variety of cargoes to many cell types	[223]
LS-CPP	CAYHRLRRC	Dual-motif CPP	Specific delivery to leukemia cells	[221]
Tumor prodrug CPP	EEEEEDDDDK/ARRRRRRRRR	Prodrug with tumor environment activation	Proteases in the tumor environment cleave the sequence, removing the acidic (negative) amino acid residues	[219]
Antibody–CPP conjugate	Penetratin+MAb CC49	MAb targeted CPP	Increased tumor: normal tissue delivery ratio	[217]

This table contains representative CPPs that represent the major classes of targeted and untargeted CPPs. TAT and Penetratin are generally untargeted, although their biodistribution may cause site-selective accumulation. LS-CPP is a leukemia-specific CPP. The tumor prodrug CPP is cleaved at the ‘/’ when in the tumor environment, thus separating the negatively charged amino acids from the positively charged CPP-cargo conjugate. Antibody-targeted CPPs can be used to selectively deliver a CPP–cargo conjugate to desired cell types.

CPP: Cell-penetrating peptide; LS-CPP: Leukemia-specific cell-penetrating peptide; MAb: Monoclonal antibody; TAT: Trans-activating transcriptional activator.