ArticleMolecular cancer research : MCR2020
Ku80-Targeted pH-Sensitive Peptide-PNA Conjugates Are Tumor Selective and Sensitize Cancer Cells to Ionizing Radiation.
Article in Molecular cancer research : MCR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Engineered miR-122 inhibitors preserve endothelial mitochondrial function and prevent vascular dysfunction in obesity-associated prediabetes.Molecular therapy. Nucleic acids · 2026Article
- Gamma-FIT-PNAs as sensitive RNA probes.RSC chemical biology · 2026Article
- Advances in MicroRNA Therapy for Heart Failure: Clinical Trials, Preclinical Studies, and Controversies.Cardiovascular drugs and therapy · 2025Review
- 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
- Development of bioconjugate-based delivery systems for nucleic acids.RNA (New York, N.Y.) · 2024Review
- Enhancing Anti-Cancer Immune Response by Acidosis-Sensitive Nanobody Display.The Journal of membrane biology · 2024Article
- Nucleic acid drugs: recent progress and future perspectives.Signal transduction and targeted therapy · 2024Review
- Peptide Nucleic Acid-Mediated Regulation of CRISPR-Cas9 Specificity.Nucleic acid therapeutics · 2024Article
- Detecting theBiomolecules · 2024Article
- Therapeutic and diagnostic applications of antisense peptide nucleic acids.Molecular therapy. Nucleic acids · 2024Review
- Aiming the magic bullet: targeted delivery of imaging and therapeutic agents to solid tumors by pHLIP peptides.Frontiers in pharmacology · 2024Review
- Multivalent Lactobionic Acid and N-Acetylgalactosamine-Conjugated Peptide Nucleic Acids for Efficient In Vivo Targeting of Hepatocytes.Advanced healthcare materials · 2023Article
- Unlocking the potential of chemically modified peptide nucleic acids for RNA-based therapeutics.RNA (New York, N.Y.) · 2023Review
- Perspectives on conformationally constrained peptide nucleic acid (PNA): insights into the structural design, properties and applications.RSC chemical biology · 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
- γ Peptide Nucleic Acid-Based miR-122 Inhibition Rescues Vascular Endothelial Dysfunction in Mice Fed a High-Fat Diet.Journal of medicinal chemistry · 2022Article
- The Challenges and Opportunities in the Development of MicroRNA Therapeutics: A Multidisciplinary Viewpoint.Cells · 2021Review
- Hypoxia-Induced Cancer Cell Responses Driving Radioresistance of Hypoxic Tumors: Approaches to Targeting and Radiosensitizing.Cancers · 2021Review
- Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The development of therapeutic agents that specifically target cancer cells while sparing healthy tissue could be used to enhance the efficacy of cancer therapy without increasing its toxicity. Specific targeting of cancer cells can be achieved through the use of pH-low insertion peptides (pHLIP), which take advantage of the acidity of the tumor microenvironment to deliver cargoes selectively to tumor cells. We developed a pHLIP-peptide nucleic acid (PNA) conjugate as an antisense reagent to reduce expression of the otherwise undruggable DNA double-strand break repair factor, KU80, and thereby radiosensitize tumor cells. Increased antisense activity of the pHLIP-PNA conjugate was achieved by partial mini-PEG sidechain substitution of the PNA at the gamma position, designated pHLIP-αKu80(γ). We evaluated selective effects of pHLIP-αKu80(γ) in cancer cells in acidic culture conditions as well as in two subcutaneous mouse tumor models. Fluorescently labeled pHLIP-αKu80(γ) delivers specifically to acidic cancer cells and accumulates preferentially in tumors when injected i.v. in mice. Furthermore, pHLIP-αKu80(γ) selectively reduced KU80 expression in cells under acidic conditions and in tumors
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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.