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Updated: Jul 15, 2026

Construction of Cyclic Cell-Penetrating Peptides for Enhanced Penetration of Biological Barriers
Published on: September 19, 2022
Cell penetrating peptides: intracellular pathways and pharmaceutical perspectives
Leena N Patel1, Jennica L Zaro, Wei-Chiang Shen
1Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California 90089, USA.
Cell penetrating peptides (CPPs) offer non-invasive macromolecule delivery. This review examines CPP internalization mechanisms and intracellular processing, crucial for selecting effective drug delivery systems.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Delivery Systems
Background:
- Cell penetrating peptides (CPPs) are emerging as non-invasive carriers for diverse cargo.
- Their amphipathic or cationic nature influences their function.
- Despite extensive research, CPP internalization mechanisms remain debated, with endocytosis involvement unclear.
Purpose of the Study:
- To critically evaluate methodologies used to study CPP internalization.
- To provide a novel perspective on the intracellular processing of CPPs.
- To review recent applications of CPPs in delivering various therapeutic agents.
Main Methods:
- Review of existing literature on CPP internalization mechanisms.
- Analysis of methodological challenges in studying CPP uptake.
- Discussion of intracellular processing pathways.
Main Results:
- Methodological limitations contribute to the lack of consensus on CPP internalization.
- Intracellular processing is a critical, often overlooked, factor in CPP-based delivery.
- CPPs have demonstrated versatility in delivering small molecules, peptides, proteins, oligonucleotides, nanoparticles, and liposomes.
Conclusions:
- Standardized methodologies are needed to elucidate CPP internalization pathways.
- Understanding intracellular processing is vital for optimizing CPP drug delivery.
- CPPs represent a promising platform for advanced therapeutic delivery systems.
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