An aptamer specifically binding the interleukin-6 receptor and intrinsically comprising multiple units of the nucleoside analogue 5-fluoro-2′-deoxyuridine can exert a cytostatic effect direcly on certain cells presenting the receptor. Thus the modified aptamer fulfils the requirements for active drug targeting in an unprecedented manner. It can easily be synthesized in a single enzymatic step and it binds to a cell surface receptor that is conveyed into the lysosome. Upon degradation of the aptamer by intracellular nucleases the active drug is released within the targeted cells exclusively. In this way the aptamer acts as a prodrug meeting two major prerequisites of a drug delivery system: specific cell targeting and the controlled release of the drug triggered by an endogenous stimulus.

Ein Aptamer, das spezifisch an den Interleukin-6-Rezeptor bindet und intrinsisch mehrere Einheiten des Nukleosidanalogons 5-Fluor-2′-desoxyuridin beinhaltet, ist in der Lage, gezielt einen zytostatischen Effekt auf Zellen auszuüben, die diesen Rezeptor tragen. Das Aptamer kann in einem einzigen enzymatischen Schritt synthetisiert werden und bindet an einen Zelloberflächenrezeptor, der in das Lysosom transportiert wird. Ausschließlich dort in den Zielzellen führt der Abbau durch intrazelluläre Nukleasen zur Freisetzung des aktivierten Wirkstoffs. Dadurch erfüllt das Aptamer als Prodrug zwei grundlegende Voraussetzungen eines Systems zur gezielten Pharmakotherapie: das spezifische Ansteuern von Zielzellen und die durch einen endogenen Stimulus ausgelöste kontrollierte Wirkstoff-Freisetzung.

The benefits of directed and selective therapy for systemic treatment are reasons for increased interest in exploiting aptamers for cell-specific drug delivery. Nucleic acid based pharmaceuticals represent an interesting and novel tool to counter human diseases. Combining inhibitory potential and cargo transfer upon internalization, nanocarriers as well as various therapeutics including siRNAs, chemotherapeutics, photosensitizers, or proteins can be imported via these synthetic nucleic acids. However, widespread clinical application is still hampered by obstacles that must be overcome. In this review, we give an overview of applications and recent advances in aptamer-mediated drug delivery. We also introduce prominent selection methods as well as useful approaches in choice of drug and conjugation method. We discuss the challenges that need to be considered and present strategies that have been applied to achieve intracellular delivery of effectors transported by readily internalized aptamers.

Fucosylation is often the final process in glycan biosynthesis. The resulting glycans are involved in a variety of biological processes, such as cell adhesion, inflammation, or tumor metastasis. Fucosyltransferases catalyze the transfer of fucose residues from the activated donor molecule GDP-β-L-fucose to various acceptor molecules. However, detailed information about the reaction processes is still lacking for most fucosyltransferases. In this work we have monitored α1,3-fucosyltransferase activity. For both donor and acceptor substrates, the introduction of a fluorescent ATTO dye was the last step in the synthesis. The subsequent conversion of these substrates into fluorescently labeled products by α1,3-fucosyltransferases was examined by high-performance thin-layer chromatography coupled with mass spectrometry as well as dual-color fluorescence cross-correlation spectroscopy, which revealed that both fluorescently labeled donor GDP-β-L-fucose-ATTO 550 and acceptor N-acetyllactosamine-ATTO 647N were accepted by recombinant human fucosyltransferase IX and Helicobacter pylori α1,3-fucosyltransferase, respectively. Analysis by fluorescence cross-correlation spectroscopy allowed a quick and versatile estimation of the progress of the enzymatic reaction and therefore this method can be used as an alternative method for investigating fucosyltransferase reactions.