globalchange  > 气候变化与战略
DOI: 10.1073/pnas.2016605118
论文题名:
Pharmacokinetic modeling reveals parameters that govern tumor targeting and delivery by a pH-Low Insertion Peptide (pHLIP)
作者: Svoronos A.A.; Engelman D.M.
刊名: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
出版年: 2021
卷: 118, 期:1
语种: 英语
英文关键词: PH-Low Insertion Peptide ; Pharmacokinetic modeling ; PHLIP ; Tumor acidity ; Tumortargeted drug delivery
英文摘要: 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. © 2021 National Academy of Sciences. All rights reserved.
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资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/163349
Appears in Collections:气候变化与战略

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作者单位: Svoronos, A.A., Department of Biomedical Engineering, Yale University, New Haven, CT 06511, United States, Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, United States; Engelman, D.M., Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, United States

Recommended Citation:
Svoronos A.A.,Engelman D.M.. Pharmacokinetic modeling reveals parameters that govern tumor targeting and delivery by a pH-Low Insertion Peptide (pHLIP)[J]. Proceedings of the National Academy of Sciences of the United States of America,2021-01-01,118(1)
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