For the design of a biohybrid structure as a ligand-tailored drug delivery system (DDS), it is highly sophisticated to fabricate a DDS based on smoothly controllable conjugation steps. This article reports on the synthesis and the characterization of biohybrid conjugates based on noncovalent conjugation between a multivalent biotinylated and PEGylated poly(amido amine) (PAMAM) dendrimer and a tetrameric streptavidin-small protein binding scaffold. This protein binding scaffold (SA-ABDwt) possesses nM affinity toward human serum albumin (HSA). Thus, well-defined biohybrid structures, finalized by binding of one or two HSA molecules, are available at each conjugation step in a controlled molar ratio. Overall, these biohybrid assemblies can be used for (i) a controlled modification of dendrimers with the HSA molecules to increase their blood-circulation half-life and passive accumulation in tumor; (ii) rendering dendrimers a specific affinity to various ligands based on mutated ABD domain, thus replacing tedious dendrimer-antibody covalent coupling and purification procedures.

Department of Biology Faculty of Science University of J E Purkinje 400 96 Ústí nad Labem Czech Republic

Institute of Biotechnology CAS v v i Pru˚myslová 595 Vestec 252 42 Jesenice u Prahy Czech Republic

Institute of Chemical Process Fundamentals CAS v v i Rozvojová 135 165 02 Prague Czech Republic

Institute of Microbiology CAS v v i Vídeˇnská 1083 142 20 Prague Czech Republic

Leibniz Institute of Polymer Research Dresden Hohe Straße 6 D 01069 Dresden Germany

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