Development of colloids for cell and tissue targeting: bisphosphonate-functionalized gold nanoparticles for the investigation of bone targeting

摘要: Gold nanoparticles (GNPs) possess a great potential as model systems for the investigation of nanoparticulate drug delivery due to their ease production, low toxicity and also high stability noble metal in biological fluids. Due unique surface chemistry, they can be used building platform stable self assembled monolayers thioalkylated poly(ethylene glycol)s with different functionalities, allowing targeting principles. In this thesis gold nanoparticles, suitable intravenous vivo applications, were prepared aqueous media by citrate reduction chloride, yielding particles size range 40 150 nm appropriate distributions. Adjustment particle was achieved varying ratio salt subsequently obtained investigated via photon correlation spectroscopy transmission electron microscopy sufficient determination. For subsequent stabilization functionalization, heterobifunctional glycol) derivatives [PEG] synthesized, carrying thioalkyl chain binding hydrophilic PEG coating. The synthesis further improved applying new synthetic strategy, order avoid non polymer components interfering For additional functionalization ligands, polymers furthermore modified provide functional amine group, which attach molecules necessary specific colloids target sites. In two [methoxy glycol)-undecyl mercaptane amino mercaptane] synthesized conjugated bone ligand, namely bisphosphonate, using standard DCC/NHS chemistry. characterized 1H-NMR, HPLC mass demonstrated degree purity, immobilization on surfaces. In functionalize particles, bisphosphonate methoxy terminated (BP-PEG-AlkSH mPEG-AlkSH) mixed ratios coat nanoparticles. investigations that coated slightly increased determined PCS, but no significant changes observed TEM contrast layer. charge UV-Vis absorption spectra only changed, indicating well separated successful replacement coating polymers. polymer-coated proved (5M NaCl, 200 µg/ml BSA 10% (V/V) serum), strong established steric uncharged Bisphosphonate incubated porous hydroxyapatite ceramics (Endobon®, Biomet) it adsorption apatite strongly dependent content not affected calcium ions or proteins added media. The conducted radioactively labeled indicated functionalized non-functionalized showed minimum uptake reticuloendothelial system (liver spleen) therefore circulated very long time bloodstream compared other systems. On hand tendency extravasate distribute into organs after injection mice, largest accumulation kidneys. Besides steady comparison control studies have investigate especially term fate accurate location kidney. Due beneficial behavior developed here presented may active strategies many fields.