ArticleJournal of controlled release : official journal of the Controlled Release Society2011
Cellular uptake of cyclotide MCoTI-I follows multiple endocytic pathways.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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The trial behind it
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Who cites it
47 citing papers in PubMed, 110 citations in OpenAlex.
- Fighting the invader: strategies against intracellular bacteria.Frontiers in pharmacology · 2026Review
- Plant Defense Peptides: Exploring the Structure-Function Correlation for Potential Applications in Drug Design and Therapeutics.ACS omega · 2025Review
- Small and Versatile Cyclotides as Anti-infective Agents.ACS infectious diseases · 2025Review
- Molecular Chimera in Cancer Drug Discovery: Beyond Antibody Therapy, Designing Grafted Stable Peptides Targeting Cancer.International journal of peptide research and therapeutics · 2025Review
- Research Progress on Cyclic-Peptide Functionalized Nanoparticles for Tumor-Penetrating Delivery.International journal of nanomedicine · 2024Review
- Resistance is futile: targeting multidrug-resistant bacteria withRSC chemical biology · 2023Review
- Native and Engineered Cyclic Disulfide-Rich Peptides as Drug Leads.Molecules (Basel, Switzerland) · 2023Review
- Review
- Using the Cyclotide Scaffold for Targeting Biomolecular Interactions in Drug Development.Molecules (Basel, Switzerland) · 2022Review
- Targeting intracellular protein-protein interactions with macrocyclic peptides.Trends in pharmacological sciences · 2022Review
- Importance of the Cyclic Cystine Knot Structural Motif for Immunosuppressive Effects of Cyclotides.ACS chemical biology · 2021Article
- Engineered Cyclotides with Potent Broad in Vitro and in Vivo Antimicrobial Activity.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Cellular Uptake and Cytosolic Delivery of a Cyclic Cystine Knot Scaffold.ACS chemical biology · 2020Article
- Recombinant Expression of Cyclotides Using Expressed Protein Ligation.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Understanding Cell Penetration of Cyclic Peptides.Chemical reviews · 2019Review
- Visualizing the cellular route of entry of a cystine-knot peptide with Xfect transfection reagent by electron microscopy.Scientific reports · 2019Article
- The Potential of the Cyclotide Scaffold for Drug Development.Biomedicines · 2019Review
- The Membrane-Active Phytopeptide Cycloviolacin O2 Simultaneously Targets HIV-1-infected Cells and Infectious Viral Particles to Potentiate the Efficacy of Antiretroviral Drugs.Medicines (Basel, Switzerland) · 2019Article
- Using backbone-cyclized Cys-rich polypeptides as molecular scaffolds to target protein-protein interactions.The Biochemical journal · 2019Review
- Designing macrocyclic disulfide-rich peptides for biotechnological applications.Nature chemical biology · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cyclotides are plant-derived proteins that naturally exhibit various biological activities and whose unique cyclic structure makes them remarkably stable and resistant to denaturation or degradation. These attributes, among others, make them ideally suited for use as drug development tools. This study investigated the cellular uptake of cyclotide, MCoTI-I in live HeLa cells. Using real time confocal fluorescence microscopy imaging, we show that MCoTI-I is readily internalized in live HeLa cells and that its endocytosis is temperature-dependent. Endocytosis of MCoTI-I in HeLa cells is achieved primarily through fluid-phase endocytosis, as evidenced by its significant colocalization with 10K-dextran, but also through other pathways as well, as evidenced by its colocalization with markers for cholesterol-dependent and clathrin-mediated endocytosis, cholera toxin B and EGF respectively. Uptake does not appear to occur only via macropinocytosis as inhibition of this pathway by Latrunculin B-induced disassembly of actin filaments did not affect MCoTI-I uptake and treatment with EIPA which also seemed to inhibit other pathways collectively inhibited approximately 80% of cellular uptake. As well, a significant amount of MCoTI-I accumulates in late endosomal and lysosomal compartments and MCoTI-I-containing vesicles continue to exhibit directed movements. These findings demonstrate internalization of MCoTI-I through multiple endocytic pathways that are dominant in the cell type investigated, suggesting that this cyclotide has ready access to general endosomal/lysosomal pathways but could readily be re-targeted to specific receptors through addition of targeting ligands.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.