ArticleMolecular pharmaceutics2015
Inhibition of cancer cell proliferation and breast tumor targeting of pHLIP-monomethyl auristatin E conjugates.
Article in Molecular pharmaceutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 65 citations in OpenAlex.
- Rational design of a protein-protein interaction inhibitor that activates Protein Tyrosine Phosphatase 1B.bioRxiv : the preprint server for biology · 2026Article
- Engraftment of a surrogate antigen onto tumor cell surface via pHLIP peptide to universally target CAR-T cell therapy to solid tumors.Cancer letters · 2025Article
- Selective Recruitment of Antibodies to Cancer Cells and Immune Cell-mediated Killing via In Situ Click Chemistry.ChemMedChem · 2024Article
- Enhancing Anti-Cancer Immune Response by Acidosis-Sensitive Nanobody Display.The Journal of membrane biology · 2024Article
- Aiming the magic bullet: targeted delivery of imaging and therapeutic agents to solid tumors by pHLIP peptides.Frontiers in pharmacology · 2024Review
- Targeted acidosis mediated delivery of antigenic MHC-binding peptides.Frontiers in immunology · 2024Article
- Promoting the activity of a receptor tyrosine phosphatase with a novel pH-responsive transmembrane agonist inhibits cancer-associated phenotypes.Protein science : a publication of the Protein Society · 2023Article
- Antibody-Drug Conjugates in Solid Tumor Oncology: An Effectiveness Payday with a Targeted Payload.Pharmaceutics · 2023Review
- Recent Advances of Studies on Cell-Penetrating Peptides Based on Molecular Dynamics Simulations.Cells · 2022Review
- Selective Display of a Chemoattractant Agonist on Cancer Cells Activates the Formyl Peptide Receptor 1 on Immune Cells.Chembiochem : a European journal of chemical biology · 2022Article
- PET Imaging of Acidic Tumor Environment WithFrontiers in oncology · 2022Article
- Roles of key residues and lipid dynamics reveal pHLIP-membrane interactions at intermediate pH.Biophysical journal · 2021Article
- Discovery of Dolastatinol: A Synthetic Analog of Dolastatin 10 and Low Nanomolar Inhibitor of Tubulin Polymerization.ACS medicinal chemistry letters · 2021Article
- Review
- An Experimental Study on [Molecular imaging · 2021Article
- Using Simulation to Understand the Role of Titration on the Stability of a Peptide-Lipid Bilayer Complex.Langmuir : the ACS journal of surfaces and colloids · 2020Article
- Ku80-Targeted pH-Sensitive Peptide-PNA Conjugates Are Tumor Selective and Sensitize Cancer Cells to Ionizing Radiation.Molecular cancer research : MCR · 2020Article
- pH-Dependent Grafting of Cancer Cells with Antigenic Epitopes Promotes Selective Antibody-Mediated Cytotoxicity.Journal of medicinal chemistry · 2020Article
- pHLIP(Var7)-P1AP suppresses tumor cell proliferation in MDA-MB-231 triple-negative breast cancer by targeting protease activated receptor 1.Breast cancer research and treatment · 2020Article
- Tumor-Targeted, Cytoplasmic Delivery of Large, Polar Molecules Using a pH-Low Insertion Peptide.Molecular pharmaceutics · 2020Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Localized delivery is vital for the successful development of novel and effective therapeutics for the treatment of cancer. The targeting and delivery described herein is based on the pH (low) insertion peptide (pHLIP), a unique delivery peptide that can selectively target tumors in mice and translocate and release cargo molecules intracellularly based solely on the low extracellular pH intrinsic to cancer cells. In this study, we investigate the efficacy of pHLIP to target and deliver the highly potent and clinically validated microtubule inhibitor monomethyl auristatin E (MMAE) to cancer cells and breast tumors. We show that pHLIP-MMAE conjugates induce a potent cytotoxic effect (>90% inhibition of cell growth) in a concentration- and pH-dependent manner after only 2 h incubation without any apparent disruption of the plasma membrane. pHLIP-MMAE conjugates exhibit between an 11- and 144-fold higher antiproliferative effect at low pH than that at physiological pH and a pronounced pH-dependent cytotoxicity as compared to that of free drug. Furthermore, we demonstrate that a pHLIP-MMAE drug conjugate effectively targets triple-negative breast tumor xenografts in mice. These results indicate that pHLIP-based auristatin conjugates may have an enhanced therapeutic window as compared to that of free drug, providing a targeting mechanism to attenuate systemic toxicity.
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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.