气候变化领域集成服务门户(CCPortal): Pharmacokinetic modeling reveals parameters that govern tumor targeting and delivery by a pH-Low Insertion Peptide (pHLIP)

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DOI	10.1073/pnas.2016605118
	Pharmacokinetic modeling reveals parameters that govern tumor targeting and delivery by a pH-Low Insertion Peptide (pHLIP)
	Svoronos A.A.; Engelman D.M.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:1
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.
英文关键词	PH-Low Insertion Peptide; Pharmacokinetic modeling; PHLIP; Tumor acidity; Tumortargeted drug delivery
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/160184
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
推荐引用方式 GB/T 7714	Svoronos A.A.,Engelman D.M.. Pharmacokinetic modeling reveals parameters that govern tumor targeting and delivery by a pH-Low Insertion Peptide (pHLIP)[J],2021,118(1).
APA	Svoronos A.A.,&Engelman D.M..(2021).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,118(1).
MLA	Svoronos A.A.,et al."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 118.1(2021).