G protein-coupled receptors function as logic gates for nanoparticle binding and cell uptake

Hild W.; Pollinger K.; Caporale A.Cabrele C.Keller M.Pluym N.Buschauer A.Rachel R.Tessmar J.Breunig M.Goepferich A.

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G protein-coupled receptors function as logic gates for nanoparticle binding and cell uptake

机译：G protein-coupled receptors function as logic gates for nanoparticle binding and cell uptake

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More selective interactions of nanoparticles with cells would substantially increase their potential for diagnostic and therapeutic applications. Thus, it would not only be highly desirable that nanoparticles can be addressed to any cell with high target specificity and affinity, but that we could unequivocally define whether they rest immobilized on the cell surface as a diagnostic tag, or if they are internalized to serve as a delivery vehicle for drugs. To date no class of targets is known that would allow direction of nanoparticle interactions with cells alternatively into one of these mutually exclusive events. Using MCF-7 breast cancer cells expressing the human Y _1-receptor, we demonstrate that G protein-coupled receptors provide us with this option. We show that quantum dots carrying a surface-immobilized antagonist remain with nanomolar affinity on the cell surface, and particles carrying an agonist are internalized upon receptor binding. The receptor functions like a logic "and-gate" that grants cell access only to those particles that carry a receptor ligand "and" where the ligand is an agonist. We found that agonist- and antagonist-modified nanoparticles bind to several receptor molecules at a time. This multiligand binding leads to five orders of magnitude increased-receptor affinities, compared with free ligand, in displacement studies. More than 800 G protein-coupled receptors in humans provide us with the paramount advantage that targeting of a plethora of cells is possible, and that switching from cell recognition to cell uptake is simply a matter of nanoparticle surface modification with the appropriate choice of ligand type.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2010年第23期|10667-10672|共6页
作者
Hild W.; Pollinger K.; Caporale A.Cabrele C.Keller M.Pluym N.Buschauer A.Rachel R.Tessmar J.Breunig M.Goepferich A.;
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作者单位

Department of Pharmaceutical Technology, University of Regensburg, 93053 Regensburg, Germany;

Department of Pharmaceutical and Medicinal Chemistry, University of Regensburg, 93053 Regensburg, Germany;

Center for Electron Microscopy, Institute for Anatomy, University of Regensburg, 93053 Regensburg, GermanyDepartment of Organic Chemistry, Ruhr-University Bochum, 44801 Bochum, Germany;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Cell membrane binding; Drug delivery; Nanoparticle receptor interaction; Nanoparticle targeting; Quantum dots;

G protein-coupled receptors function as logic gates for nanoparticle binding and cell uptake

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