ArticleProceedings of the National Academy of Sciences of the United States of America2015
The pH low insertion peptide pHLIP Variant 3 as a novel marker of acidic malignant lesions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 68 citations in OpenAlex.
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- Nanomaterial isolated extracellular vesicles enable high precision identification of tumor biomarkers for pancreatic cancer liquid biopsy.Journal of nanobiotechnology · 2025Article
- Tumor-Specific Antigen Delivery for T-cell Therapy via a pH-Sensitive Peptide Conjugate.Molecular cancer therapeutics · 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
- Peptide-based capture-and-release purification of extracellular vesicles and statistical algorithm enabled quality assessment.bioRxiv : the preprint server for biology · 2024Article
- Aiming the magic bullet: targeted delivery of imaging and therapeutic agents to solid tumors by pHLIP peptides.Frontiers in pharmacology · 2024Review
- Article
- Arginine Residues Modulate the Membrane Interactions of pHLIP Peptides.Journal of chemical information and modeling · 2023Article
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- CaProtein science : a publication of the Protein Society · 2022Article
- Efficient Delivery of Curcumin by Alginate Oligosaccharide Coated Aminated Mesoporous Silica Nanoparticles and In Vitro Anticancer Activity against Colon Cancer Cells.Pharmaceutics · 2022Article
- Eradication of tumors and development of anti-cancer immunity using STINGa targeted by pHLIP.Frontiers in oncology · 2022Article
- PET Imaging of Acidic Tumor Environment WithFrontiers in oncology · 2022Article
- Pharmacokinetic modeling reveals parameters that govern tumor targeting and delivery by a pH-Low Insertion Peptide (pHLIP).Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- An Experimental Study on [Molecular imaging · 2021Article
- pHLIP ICG for delineation of tumors and blood flow during fluorescence-guided surgery.Scientific reports · 2020Article
- T-cells produce acidic niches in lymph nodes to suppress their own effector functions.Nature communications · 2020Article
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- iNOS Regulates the Therapeutic Response of Pancreatic Cancer Cells to Radiotherapy.Cancer research · 2020Article
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 2 countries.
Funding
Abstract
Current strategies for early detection of breast and other cancers are limited in part because some lesions identified as potentially malignant do not develop into aggressive tumors. Acid pH has been suggested as a key characteristic of aggressive tumors that might distinguish aggressive lesions from more indolent pathology. We therefore investigated the novel class of molecules, pH low insertion peptides (pHLIPs), as markers of low pH in tumor allografts and of malignant lesions in a mouse model of spontaneous breast cancer, BALB/neu-T. pHLIP Variant 3 (Var3) conjugated with fluorescent Alexa546 was shown to insert into tumor spheroids in a sequence-specific manner. Its signal reflected pH in murine tumors. It was induced by carbonic anhydrase IX (CAIX) overexpression and inhibited by acetazolamide (AZA) administration. By using (31)P magnetic resonance spectroscopy (MRS), we demonstrated that pHLIP Var3 was retained in tumors of pH equal to or less than 6.7 but not in tissues of higher pH. In BALB/neu-T mice at different stages of the disease, the fluorescent signal from pHLIP Var3 marked cancerous lesions with a very low false-positive rate. However, only ∼60% of the smallest lesions retained a pHLIP Var3 signal, suggesting heterogeneity in pH. Taken together, these results show that pHLIP can identify regions of lower pH, allowing for its development as a theranostic tool for clinical applications.
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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.