Biocompatible Size-Defined Dendrimer-Albumin Binding Protein Hybrid Materials as a Versatile Platform for Biomedical Applications.

Abstract

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.

• Authors: Jan Maly, Ondrej Stanek, Jan Frolik, Marek Maly, Franka Ennen, Dietmar Appelhans, Alena Semeradtova, Dominika Wrobel, Marcel Stofik, Tereza Knapova, Milan Kuchar, Lucie Cervenkova Stastna, Jan Cermak, Peter Sebo, Petr Maly
• Journal: Macromolecular bioscience (Macromol Biosci) Vol. 16 Issue 4 Pg. 553-66 (Apr 2016) ISSN: 1616-5195 [Electronic] Germany
• PMID: 26748571 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Bacterial Proteins
• Dendrimers
• Ligands
• PAMAM Starburst
• Polyamines
• Recombinant Fusion Proteins
• Serum Albumin
• Polyethylene Glycols
• Biotin
• Streptavidin

Topics

• Amino Acid Sequence
• Animals
• Bacterial Proteins (genetics, metabolism)
• Biotin (chemistry)
• Biotinylation
• Cell Line
• Dendrimers (chemical synthesis, pharmacology)
• Drug Delivery Systems
• Epithelial Cells (cytology, drug effects)
• Escherichia coli (genetics, metabolism)
• Gene Expression
• Humans
• Ligands
• Models, Molecular
• Nanoparticles (chemistry, ultrastructure)
• Polyamines (chemistry)
• Polyethylene Glycols (chemistry)
• Protein Binding
• Rats
• Recombinant Fusion Proteins (genetics, metabolism)
• Serum Albumin (chemistry)
• Streptavidin (chemistry)
• Streptomyces (genetics, metabolism)