ArticleBiochemistry2014
Early endosomal escape of a cyclic cell-penetrating peptide allows effective cytosolic cargo delivery.
Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed.
- Protein Modifications for Cellular Protein Delivery.Chemical reviews · 2026Review
- SSEL-CPP: A SHAP-based feature-selection ensemble learning framework identifies molecular properties of cell-penetrating peptides.Protein science : a publication of the Protein Society · 2026Article
- Macrocyclic Peptides Containing an Imidazopyridinium (IPJournal of the American Chemical Society · 2026Article
- Macrocyclic Peptides Containing an Imidazopyridinium (IPbioRxiv : the preprint server for biology · 2025Article
- Peptide-Based Inorganic Nanoparticles as Efficient Intracellular Delivery Systems.Pharmaceutics · 2025Review
- Clinical applications of exon-skipping antisense oligonucleotides in neuromuscular diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Advances in Cytosolic Delivery of Proteins: Approaches, Challenges, and Emerging Technologies.Chemistry & biodiversity · 2025Review
- Nanoimmunotherapy: the smart trooper for cancer therapy.Exploration of targeted anti-tumor therapy · 2025Review
- Endosomal Escape and Nuclear Localization: Critical Barriers for Therapeutic Nucleic Acids.Molecules (Basel, Switzerland) · 2024Review
- Cell-Penetrating Peptides Translocate across the Plasma Membrane by Inducing Vesicle Budding and Collapse.Journal of the American Chemical Society · 2024Article
- Discovery and Development of Cyclic Peptide Proteasome Stimulators.Chembiochem : a European journal of chemical biology · 2024Article
- PractiCPP: a deep learning approach tailored for extremely imbalanced datasets in cell-penetrating peptide prediction.Bioinformatics (Oxford, England) · 2024Article
- Intracellular Protein Delivery: Approaches, Challenges, and Clinical Applications.BME frontiers · 2024Review
- Targeting the ExpandedACS omega · 2023Article
- Cell-Surface-Retained Peptide Additives for the Cytosolic Delivery of Functional Proteins.Journal of the American Chemical Society · 2023Article
- The endosomal escape vehicle platform enhances delivery of oligonucleotides in preclinical models of neuromuscular disorders.Molecular therapy. Nucleic acids · 2023Article
- Cell-Penetrating and Targeted Peptides Delivery Systems as Potential Pharmaceutical Carriers for Enhanced Delivery across the Blood-Brain Barrier (BBB).Pharmaceutics · 2023Review
- Cell-Penetrating Peptide-Based Delivery of Macromolecular Drugs: Development, Strategies, and Progress.Biomedicines · 2023Review
- Development of a Cyclic, Cell Penetrating Peptide Compatible with In Vitro Selection Strategies.ACS chemical biology · 2023Article
- Recent Trends in Antisense Therapies for Duchenne Muscular Dystrophy.Pharmaceutics · 2023Review
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Cyclic heptapeptide cyclo(FΦRRRRQ) (cFΦR4, where Φ is l-2-naphthylalanine) was recently found to be efficiently internalized by mammalian cells. In this study, its mechanism of internalization was investigated by perturbing various endocytic events through the introduction of pharmacologic agents and genetic mutations. The results show that cFΦR4 binds directly to membrane phospholipids, is internalized into human cancer cells through endocytosis, and escapes from early endosomes into the cytoplasm. Its cargo capacity was examined with a wide variety of molecules, including small-molecule dyes, linear and cyclic peptides of various charged states, and proteins. Depending on the nature of the cargos, they may be delivered by endocyclic (insertion of cargo into the cFΦR4 ring), exocyclic (attachment of cargo to the Gln side chain), or bicyclic approaches (fusion of cFΦR4 and cyclic cargo rings). The overall delivery efficiency (i.e., delivery of cargo into the cytoplasm and nucleus) of cFΦR4 was 4-12-fold higher than those of nonaarginine, HIV Tat-derived peptide, or penetratin. The higher delivery efficiency, coupled with superior serum stability, minimal toxicity, and synthetic accessibility, renders cFΦR4 a useful transporter for intracellular cargo delivery and a suitable system for investigating the mechanism of endosomal escape.
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Registered trials
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