Cell penetrating peptides are short protein fragments that can cross cell membranes, acting as delivery vehicles to carry drugs, genes, proteins, and nanoparticles into cells that they couldn't otherwise enter.
Versatile intracellular delivery vehiclesCPPs can transport nucleic acids, proteins, siRNA, small molecule drugs, and nanoparticles across cell membranes — making them one of the most adaptable delivery tools in biomedical research
What the researchers found
Cell penetrating peptides (CPPs) are short peptide sequences that can cross cell membranes — a feat that most therapeutic molecules cannot accomplish. This review classifies CPPs into categories based on their origin and properties, describes their uptake mechanisms (direct penetration vs. endocytosis), and catalogs their biomedical applications as delivery vehicles for nucleic acids, proteins, siRNA, drugs, and nanoparticles.
The key insight is that CPPs can carry virtually any type of therapeutic cargo across cell membranes, making them one of the most versatile drug delivery tools in biomedical research.
Why it matters
Getting drugs inside cells is one of the biggest challenges in medicine. Many promising therapeutics — gene therapies, siRNA, proteins — can't cross cell membranes to reach their targets. CPPs solve this problem by acting as molecular taxis, ferrying cargo through the membrane barrier. This technology underpins a wide range of emerging therapies from cancer treatment to gene editing.
The numbers in context
Review covering 20+ years of CPP research · cargo types: nucleic acids, proteins, siRNA, drugs, nanoparticles · multiple CPP classes and uptake mechanisms reviewed
How the study worked
Narrative review synthesizing the CPP literature. The authors describe CPP classification schemes (cationic, amphipathic, hydrophobic), uptake mechanisms (direct penetration, endocytosis-dependent pathways), and biomedical applications across drug delivery, gene therapy, and diagnostic imaging.
Who was studied
Review of preclinical and biomedical CPP research literature
What this study cannot tell us
As a concise review, it doesn't cover all CPPs or applications exhaustively. The review primarily describes in vitro and preclinical evidence — few CPP-based therapeutics have reached clinical approval. Endosomal entrapment (where cargo gets stuck after uptake) is a major unresolved challenge that is not deeply explored. The review is from 2018 and doesn't capture more recent developments.
How to read the evidence
This is a well-cited review covering an established field of research. The existence and utility of CPPs is well-proven in vitro and in animal models. However, clinical translation remains limited, and the review doesn't present new data. Moderate evidence for the field overall.
When this study was published
Published in 2018. The CPP field has continued to advance, with improvements in endosomal escape, cell-specific targeting, and clinical translation. The fundamental concepts described remain accurate and relevant.
The bigger picture
CPPs are a foundational technology in modern drug delivery. As medicine moves toward increasingly sophisticated intracellular therapies — gene editing, mRNA therapeutics, targeted protein degradation — the ability to get these tools inside cells becomes critical. CPPs represent one of the most promising solutions, and understanding their biology is essential for anyone working in pharmaceutical development or biomedical engineering.
Questions still open
- How can the endosomal escape problem be solved to improve the efficiency of CPP-mediated delivery?
- Can CPPs be engineered to target specific cell types rather than entering all cells indiscriminately?
- What safety concerns arise from widespread cellular penetration in a therapeutic context?
Common questions
What are cell penetrating peptides made of?
Why can't most drugs get inside cells on their own?
Read the original research
Cell penetrating peptides: A concise review with emphasis on biomedical applications.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 108, 1090-1096
Citation
Derakhshankhah, Hossein; Jafari, Samira. (2018). Cell penetrating peptides: A concise review with emphasis on biomedical applications.. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 108, 1090-1096. https://doi.org/10.1016/j.biopha.2018.09.097