气候变化领域集成服务门户(CCPortal): Peptides of pHLIP family for targeted intracellular and extracellular delivery of cargo molecules to tumors

CCPortal

DOI	10.1073/pnas.1715350115
	Peptides of pHLIP family for targeted intracellular and extracellular delivery of cargo molecules to tumors
	Wyatt L.C.; Moshnikova A.; Crawford T.; Engelman D.M.; Andreev O.A.; Reshetnyak Y.K.
发表日期	2018
ISSN	0027-8424
起始页码	E2811
结束页码	E2818
卷号	115 期号:12
英文摘要	The pH (low) insertion peptides (pHLIPs) target acidity at the surfaces of cancer cells and show utility in a wide range of applications, including tumor imaging and intracellular delivery of therapeutic agents. Here we report pHLIP constructs that significantly improve the targeted delivery of agents into tumor cells. The investigated constructs include pHLIP bundles (conjugates consisting of two or four pHLIP peptides linked by polyethylene glycol) and Var3 pHLIPs containing either the nonstandard amino acid, γ-carboxyglutamic acid, or a glycine-leucine-leucine motif. The performance of the constructs in vitro and in vivo was compared with previous pHLIP variants. A wide range of experiments was performed on nine constructs including (i) biophysical measurements using steady-state and kinetic fluorescence, circular dichroism, and oriented circular dichroism to study the pH-dependent insertion of pHLIP variants across the membrane lipid bilayer; (ii) cell viability assays to gauge the pH-dependent potency of peptide-toxin constructs by assessing the intracellular delivery of the polar, cellimpermeable cargo molecule amanitin at physiological and low pH (pH 7.4 and 6.0, respectively); and (iii) tumor targeting and biodistribution measurements using fluorophore-peptide conjugates in a breast cancer mouse model. The main principles of the design of pHLIP variants for a range of medical applications are discussed. © 2018 National Academy of Sciences. All rights reserved.
英文关键词	Cytoplasmic drug delivery; Membrane-associated folding; Polar drugs; Targeted chemotherapy; Tumor acidity
语种	英语
scopus关键词	4 carboxyglutamic acid; alpha amanitin; antineoplastic agent; fluorophore peptide conjugate; glycine; leucine; macrogol; peptide; pH low insertion peptide; unclassified drug; amanitin; antineoplastic agent; liposome; membrane protein; peptide; pHLIP protein; adult; animal experiment; animal model; animal tissue; Article; breast cancer; cell viability assay; circular dichroism; controlled study; cytotoxicity; drug delivery system; drug distribution; drug mechanism; female; fluorescence analysis; in vitro study; in vivo study; lipid bilayer; molecularly targeted therapy; mouse; mouse model; nonhuman; peptide analysis; pH measurement; priority journal; protein motif; steady state; animal; Bagg albino mouse; chemistry; drug delivery system; experimental neoplasm; genetics; HeLa cell line; human; pH; procedures; tissue distribution; Amanitins; Animals; Antineoplastic Agents; Circular Dichroism; Drug Delivery Systems; Female; HeLa Cells; Humans; Hydrogen-Ion Concentration; Lipid Bilayers; Liposomes; Membrane Proteins; Mice, Inbred BALB C; Neoplasms, Experimental; Peptides; Polyethylene Glycols; Tissue Distribution
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/160535
作者单位	Wyatt, L.C., Physics Department, University of Rhode Island, Kingston, RI 02881, United States; Moshnikova, A., Physics Department, University of Rhode Island, Kingston, RI 02881, United States; Crawford, T., Physics Department, University of Rhode Island, Kingston, RI 02881, United States; Engelman, D.M., Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, United States; Andreev, O.A., Physics Department, University of Rhode Island, Kingston, RI 02881, United States; Reshetnyak, Y.K., Physics Department, University of Rhode Island, Kingston, RI 02881, United States
推荐引用方式 GB/T 7714	Wyatt L.C.,Moshnikova A.,Crawford T.,et al. Peptides of pHLIP family for targeted intracellular and extracellular delivery of cargo molecules to tumors[J],2018,115(12).
APA	Wyatt L.C.,Moshnikova A.,Crawford T.,Engelman D.M.,Andreev O.A.,&Reshetnyak Y.K..(2018).Peptides of pHLIP family for targeted intracellular and extracellular delivery of cargo molecules to tumors.Proceedings of the National Academy of Sciences of the United States of America,115(12).
MLA	Wyatt L.C.,et al."Peptides of pHLIP family for targeted intracellular and extracellular delivery of cargo molecules to tumors".Proceedings of the National Academy of Sciences of the United States of America 115.12(2018).