The nanoparticles (NPs) surface plays an important role in the interaction of the NPs with surrounding environments, defines their fate in the biological media and it can be engineered to provide a large number of functional groups for different applications. The main topic of this thesis is the synthesis, the surface modification and the characterization of gold NPs (GNPs). The NPs were prepared with different sizes (up to 100 nm) and shapes (spherical and rods). The employed NPs were prepared originally in aqueous medium, stabilized by citric ions in case of spherical GNPs (SGNPs) and by hexadecyltrimethylammonium bromide (CTAB) in case of gold nanorods (GNRs). These ligand molecules are weakly bound to the NPs surface and thus, they are unsuitable for biomedical applications. Stabilizing of these NPs was the target of this work and then, it was achieved by exchange these ligands by other molecules with higher affinity and finally wrapping the NPs with an amphiphilic polymer (poly(isobutylene-alt-maleic anhydride) dodecylamine grafted, (PMA)). The polymer coating technique has been used over the past years for coating of NPs, which are synthesized originally, and only dispersible in organic media. The NPs obtained using this methodology are highly stable in physiological media. Aiming to use this technique in water-soluble NPs, a new round-trip process was developed using a phase transfer step before the polymer coating. The NPs were stabilized with α-metoxi-ω-thiol-poly-(ethyleneglycol)- (PEG) chains (mPEG-SH (Mw= 750 Da)) and then transferred from water to chloroform using dodecylamine (DDA). The DDA-capped NPs were coated with a modified amphiphilic polymer due to the hydrophobic interaction between the hydrophobic ligands (carbon chains) on the surface of the NPs and the hydrophobic side chains of the used polymer. The resulted polymer coated NPs were cleaned and characterized using different techniques, such as agarose gel electrophoresis, UV-Vis spectroscopy, dynamic light scattering (DLS), laser Doppler anemometry (LDA) and transmission electron microscopy (TEM). Furthermore, the surface of the polymer-coated NPs was modified using different molecular weight of PEG to provide them with higher colloidal stability and prevent the formation of the so-called protein corona. The colloidal stability of all particles was assayed against different biological media via UV-Vis spectroscopy and DLS. The toxicity of these NPs was tested in cancer and non-cancer cells lines showing no-toxicity up to 1 mg/mL concentration levels. Additionally, the effect of NPs size, shape, and surface coating on their interaction with plasma proteins and blood cells was studied. polymer coating colloidal stability doctoralThesis Polymerbeschichtung gold nanoparticles Philipps-Universität Marburg 2016-10-18 ths Prof. Parak Wolfgang Parak, Wolfgang (Prof.) monograph biocompatibility 208 application/pdf 2016-09-15 Gold-Nanopartikel: Synthese, Oberflächenmodifizierung und Funktionalisierung für biomedizinische Anwendungen Physics Physik https://archiv.ub.uni-marburg.de/diss/z2016/0671/cover.png urn:nbn:de:hebis:04-z2016-06716 2016 Publikationsserver der Universitätsbibliothek Marburg Universitätsbibliothek Marburg English Fachbereich Physik 175. 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National Institutes of Health Clinical Center (CC), National Cancer Institute (NCI) (2012) http://www.clinicaltrials.gov; identifier: NCT00356980 Soliman, Mahmoud Soliman Mahmoud https://doi.org/10.17192/z2016.0671 Physik toxicity Gold Nanoparticles: Synthesis, Surface Modification and Functionalization for Biomedical Applications PEGylation kolloidale Stabilität, Toxizität, Biokompatibilität opus:6896 Gold-Nanopartikel, PEGylierung, Phasentransfer phase transfer Die Oberfläche von Nanopartikeln (NP) spielt eine wichtige Rolle bei der Interaktion der Partikel mit ihrer Umgebung, definiert insbesondere ihr Schicksal in biologischen Medien und kann genutzt werden, um eine große Anzahl an funktionalen Gruppen aufzunehmen, die verschiedenste Anwendungsmöglichkeiten bieten. Das Hauptthema dieser Thesis ist die Synthese, die Oberflächenmodifikation sowie die Charakterisierung von Gold NP (GNP). Die Nanopartikel wurden in den gängigsten Größen (bis hin zu 100 nm Durchmesser) und Formen (sphärisch und stabförmig) synthetisiert. Die verwendeten NP wurden ursprünglich in wässriger Lösung vorbereitet, stabilisiert mittels Zitrat-Ionen im Falle der sphärischen GNP (SGNP) und mittels Cetyltrimethylammoniumbromid (CTAB) während der Synthese der stabförmigen GNP (GNR). Diese Ligandenmoleküle sind jedoch nur schwach an die Oberfläche gebunden und daher ungeeignet für biomedizinische Anwendungen der Partikel. Die Stabilisation der GNP war das Hauptziel dieser Arbeit welches durch den Austausch der vorhandenen Liganden durch andere Moleküle mit höherer Affinität zum Kern der GNP und der Anwendung eines das Partikel umgebenden, amphiphilen Polymers (poly(isobutylene-alt-maleic anhydride) dodecylamine grafted, (PMA)) erreicht wurde. Die Technik der Polymer-Beschichtung wird bereits seit Jahren erfolgreich für die Beschichtung verschiedenster NP-Systeme verwendet, welche ursprünglich in organischen Lösungsmitteln synthetisiert werden müssen und auch nur dort stabil sind. Die NP, die mittels dieser Herstellungsvariante erhalten wurden, sind höchst stabil, auch in physiologischen Medien. Um dieser Methode auch für wasserlösliche Systeme nutzen zu können, wurde ein neuartiger Ansatz mittels eines so genannten Wechsels eingeführt, welcher einen Phasentransfer vor dem eigentlichen Beschichten einführt. Zuerst wurden die NP mit Hilfe von α-metoxi-ω-thiol-poly-(ethyleneglycol)- (PEG) Ketten (mPEG-SH (Mw= 750 Da)) stabilisiert, um dann mittels Dodecylamin (DDA) von wässriger Lösung in Chloroform überführt werden zu können. Diese solcher Art DDA-beschichteten NP wurden anschließend mit einem amphiphilen Polymer vermischt und beschichtet, ermöglicht durch die hydrophobe Interaktion der Liganden (Kohlenstoff Ketten) an der Oberfläche der NP sowie den hydrophoben Seitenketten des Polymers. Die resultierenden Polymer-beschichteten-NP wurden anschließend aufgereinigt mittels Gel-Elektrophorese, charakterisiert über UV-Vis Spektroskopie sowie Dynamische Licht Streuung (DLS), Laser Doppler Anemometrie (LDA) und Transmissions Elektronen Mikroskopie (TEM). Ferner wurde die Oberfläche der NP mit PEG verschiedenster Größen modifiziert um die Bildung einer so genannten Protein-Korona zu verhindern sowie die kolloidale Stabilität zu erhöhen. Diese Stabilität wurde daraufhin in unterschiedlichen biologischen Medien mittels UV_VisSpektroskopie und DLS getestet. Außerdem wurde die Toxizität der hergestellten NP sowohl in Krebszelllinien als auch in standard-Zelllinien überprüft und als nicht toxisch eingestuft unterhalb einer Konzentration von 1 mg/mL. Außerdemwurde der Einfluss von GrÖße, Geometrie sowie Oberflächenbeschaffenheit von Nanopartikeln auf deren Interaktion mit Proteinen und Blutzellen untersucht.