Research Paper
Cell-penetrating peptides as part of therapeutics used in cancer research

https://doi.org/10.1016/j.medidd.2021.100092Get rights and content
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Highlights

  • Cell-penetrating peptides (CPPs) are versatile tools for intracellular drug delivery.

  • Still, no CPP-based therapeutic with indication in oncology is FDA approved.

  • Novel CPP-based therapeutics are in pipeline comprising CPP-drug conjugates or CPPs with intrinsic anti-cancer activity.

Abstract

Peptides have gained more and more interest as therapeutics for different fields of medical indications. Built up via a peptide bond from naturally occurring amino acids they stand out by their high target selectivity and good biocompatibility. However, using chemical peptide synthesis also modifications are easily introduced and offer various opportunities to fine-tune their activity spectrum. One of the main areas of the global peptide market is oncology and during the past years, many peptide therapeutics with anti-tumor activity have been reported that evoke metastasis in malignant cells or evasion of cell death. Cell-penetrating peptides (CPPs) are a particular group of bioactive peptides that can be naturally or synthetically derived and have the ability to autonomously translocate in cells and transport various cargoes with them. These versatile carriers have been widely used to deliver different kinds of therapeutic molecules, and have also found application in cancer research. Within this review we will summarize recent efforts made in this direction with a focus on the specific cancer indications for which CPP-related therapeutics have been developed and studied.

Abbreviations

ACM
acute myeloid leukemia
ACPP
activatable cell-penetrating peptide
ANG
Angiopep
ASO
antisense oligonucleotide
BBB
blood–brain-barrier
CPPs
cell-penetrating peptides
CPT
camptothecin
CRC
colorectal cancer
Cur
curcumin
EGFP
enhanced green fluorescent protein
EPS8
epidermal growth factor receptor pathway substrate no.8
GBM
glioblastoma
IA-TCH
intra-arterially-transient cerebral hyperfusion
Mad
multiple antigen domain
MDM
murine double minute
MMP
matrix metalloproteinase
MTX
methotrexan
NSCLC
non-small cell lung cancer
NLS
nuclear localization sequence
NRP
neuropilin
PCNA
proliferating cell nuclear antigen
PEI
polyethyleneimine
PIP2
phosphatidylinositol-bisphosphate
PPI
protein–protein interaction
PS
phosphatidylserine
PTX
paclitaxel
RNP
ribonucleoprotein
SCLC
small cell lung cancer
STAT3
signal transducer and activator of transcription 3
TLR
toll-like receptor
VEGF
vascular endothelial growth factor

Keywords

Cell-penetrating peptides
Peptide–drug conjugates
Drug delivery
Peptide therapeutics
Cancer therapy

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