ArticleProceedings of the National Academy of Sciences of the United States of America2021
Pharmacokinetic modeling reveals parameters that govern tumor targeting and delivery by a pH-Low Insertion Peptide (pHLIP).
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed, 18 citations in OpenAlex.
- CAR T-cell therapy in renal cell carcinoma: opportunities, challenges, and new strategies to overcome.Medical oncology (Northwood, London, England) · 2025Review
- Emerging Strategies to Overcome Current CAR-T Therapy Dilemmas - Exosomes Derived from CAR-T Cells.International journal of nanomedicine · 2024Review
- Bacterial delivery of therapeutic proteins to the nuclei of cancer cells.Biotechnology and bioengineering · 2023Article
- A double-switch pHLIP system enables selective enrichment of circulating tumor microenvironment-derived extracellular vesicles.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- ES-MION-Based Dual-Modality PET/MRI Probes for Acidic Tumor Microenvironment Imaging.ACS omega · 2022Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
A pH-Low Insertion Peptide (pHLIP) is a pH-sensitive peptide that undergoes membrane insertion, resulting in transmembrane helix formation, on exposure to acidity at a tumor cell surface. As a result, pHLIPs preferentially accumulate within tumors and can be used for tumor-targeted imaging and drug delivery. Here we explore the determinants of pHLIP insertion, targeting, and delivery through a computational modeling approach. We generate a simple mathematical model to describe the transmembrane insertion process and then integrate it into a pharmacokinetic model, which predicts the tumor vs. normal tissue biodistribution of the most studied pHLIP, "wild-type pHLIP," over time after a single intravenous injection. From these models, we gain insight into the various mechanisms behind pHLIP tumor targeting and delivery, as well as the various biological parameters that influence it. Furthermore, we analyze how changing the properties of pHLIP can influence the efficacy of tumor targeting and delivery, and we predict the properties for optimal pHLIP phenotypes that have superior tumor targeting and delivery capabilities compared with wild-type pHLIP.
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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 Socratic graph.