Dokumentenart: | Artikel | ||||
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Titel eines Journals oder einer Zeitschrift: | Proceedings of the National Academy of Sciences USA: PNAS | ||||
Verlag: | NATL ACAD SCIENCES | ||||
Ort der Veröffentlichung: | WASHINGTON | ||||
Band: | 107 | ||||
Nummer des Zeitschriftenheftes oder des Kapitels: | 23 | ||||
Seitenbereich: | S. 10667-10672 | ||||
Datum: | 8 Juni 2010 | ||||
Institutionen: | Biologie und Vorklinische Medizin > Institut für Anatomie Chemie und Pharmazie > Institut für Pharmazie > Lehrstuhl Pharmazeutische / Medizinische Chemie II (Prof. Buschauer) Chemie und Pharmazie > Institut für Pharmazie > Lehrstuhl Pharmazeutische Technologie (Prof. Göpferich) | ||||
Sonstige Projekte: | GRK 760, Graduiertenkolleg Medizinische Chemie | ||||
Identifikationsnummer: |
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Stichwörter / Keywords: | TARGETED DRUG-DELIVERY; NEUROPEPTIDE-Y; GOLD NANOPARTICLES; BREAST-CANCER; HIGHLY POTENT; HEPATITIS-C; Y-1-RECEPTOR; THERAPEUTICS; ENDOCYTOSIS; ANTAGONIST; nanoparticle targeting; drug delivery; quantum dots; nanoparticle receptor interaction; cell membrane binding | ||||
Dewey-Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik > 540 Chemie 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie | ||||
Status: | Veröffentlicht | ||||
Begutachtet: | Ja, diese Version wurde begutachtet | ||||
An der Universität Regensburg entstanden: | Ja | ||||
Dokumenten-ID: | 17435 |
Zusammenfassung
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 ...

Zusammenfassung
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.
Metadaten zuletzt geändert: 29 Sep 2021 07:38