ArticleProceedings of the National Academy of Sciences of the United States of America2016
Probe for the measurement of cell surface pH in vivo and ex vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 214 citations in OpenAlex.
- Applications of Nanopipettes in Scanning Ion Conductance Microscopy for High-Spatial-Resolution Topographic Imaging and Sensing in Single Cells.ACS measurement science au · 2026Review
- AuAg-Carbon-Based Quantum Dot Nanocomposites to Reduce Andrographolide's Hydrophobicity and Drug Internalization Tracking in PC-3 Cells.Nanomaterials (Basel, Switzerland) · 2026Article
- Harnessing tumor acidity: innovative lactic acid-responsive promoter enables precision control of CAR-T cell activity in solid tumors.Journal for immunotherapy of cancer · 2026Article
- The Impact of Tumor Microenvironmental Acidity on Bicalutamide Sensitivity in Prostate Cancer Cells.Prostate cancer · 2026Article
- Bright and pH-sensitive Baby Spinach aptamer with RNA triplex fusion.Nucleic acids research · 2025Article
- Tumor-Specific Antigen Delivery for T-cell Therapy via a pH-Sensitive Peptide Conjugate.Molecular cancer therapeutics · 2025Article
- 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
- Synthesis and Optimization of Ethylenediamine-Based Zwitterion on Polymer Side Chain for Recognizing Narrow Tumorous pH Windows.Biomacromolecules · 2024Article
- How the bone microenvironment shapes the pre-metastatic niche and metastasis.Nature cancer · 2024Review
- Enhanced glycolysis causes extracellular acidification and activates acid-sensing ion channel 1a in hypoxic pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Multifunctional Fluoropolymer-Engineered Magnetic Nanoparticles to Facilitate Blood-Brain Barrier Penetration and Effective Gene Silencing in Medulloblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Severely polarized extracellular acidity around tumour cells.Nature biomedical engineering · 2024Article
- A targeted fluorescent nanosensor for ratiometric pH sensing at the cell surface.Scientific reports · 2024Article
- Article
- pH-responsive i-motif-conjugated nanoparticles for MRI analysis.Sensors & diagnostics · 2024Article
- VISTA checkpoint inhibition by pH-selective antibody SNS-101 with optimized safety and pharmacokinetic profiles enhances PD-1 response.Nature communications · 2024Article
- Tumor therapy by targeting extracellular hydroxyapatite using novel drugs: A paradigm shift.Cancer medicine · 2024Article
- Targeted acidosis mediated delivery of antigenic MHC-binding peptides.Frontiers in immunology · 2024Article
- Aiming the magic bullet: targeted delivery of imaging and therapeutic agents to solid tumors by pHLIP peptides.Frontiers in pharmacology · 2024Review
- Fluorescent nano- and microparticles for sensing cellular microenvironment: past, present and future applications.Nanoscale advances · 2023Review
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
We have developed a way to measure cell surface pH by positioning a pH-sensitive fluorescent dye, seminaphtharhodafluor (SNARF), conjugated to the pH low insertion peptide (pHLIP). It has been observed that many diseased tissues are acidic and that tumors are especially so. A combination of effects acidifies tumor cell interiors, and cells pump out lactic acid and protons to maintain intracellular pH, acidifying the extracellular space. Overexpression of carbonic anhydrases on cell surfaces further contributes to acidification. Thus, the pH near tumor cell surfaces is expected to be low and to increase with distance from the membrane, so bulk pH measurements will not report surface acidity. Our new surface pH-measurement tool was validated in cancer cells grown in spheroids, in mouse tumor models in vivo, and in excised tumors. We found that the surface pH is sensitive to cell glycolytic activity: the pH decreases in high glucose and increases if glucose is replaced with nonmetabolized deoxyglucose. For highly metastatic cancer cells, the pH measured at the surface was 6.7-6.8, when the surrounding external pH was 7.4. The approach is sensitive enough to detect 0.2-0.3 pH unit changes in vivo in tumors induced by i.p. injection of glucose. The pH at the surfaces of highly metastatic cells within tumors was found to be about 6.1-6.4, whereas in nonmetastatic tumors, it was 6.7-6.9, possibly creating a way to distinguish more aggressive from less aggressive tumors. Other biological roles of surface acidity may be found, now that targeted measurements are possible.
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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.