PEGylated Cationic Serum Albumin for Boosting Retroviral Gene Transfer.

Retroviral vectors are common tools for introducing genes into the genome of a cell. However, low transduction rates are a major limitation in retroviral gene transfer, especially in clinical applications. We generated cationic human serum albumin (cHSA) protected by a shell of poly(ethylene glycol) (PEG); this significantly enhanced retroviral gene transduction with potentially attractive pharmacokinetics and low immunogenicity.

Efficient delivery of p53 and cytochrome c by supramolecular assembly of a dendritic multi-domain delivery system.

Versatile nanocarrier systems facilitating uptake of exogenous proteins are highly alluring in evaluating these proteins for therapeutic applications. The self-assembly of an efficient nano-sized protein transporter consisting of three different entities is presented: A streptavidin protein core functioning as an adapter, second generation polyamidoamine dendrons for facilitating cell uptake as well as two different therapeutic proteins (tumor suppressor p53 or pro-apoptotic cytochrome c as cargo). Well-defined dendrons containing a biotin core are prepared and display no cytotoxic behavior upon conjugation to streptavidin.

A core-shell albumin copolymer nanotransporter for high capacity loading and two-step release of doxorubicin with enhanced anti-leukemia activity.

The native transportation protein serum albumin represents an attractive nano-sized transporter for drug delivery applications due to its beneficial safety profile. Existing albumin-based drug delivery systems are often limited by their low drug loading capacity as well as noticeable drug leakage into the blood circulation. Therefore, a unique albumin-derived core-shell doxorubicin (DOX) delivery system based on the protein denaturing-backfolding strategy was developed.

A quantum dot photoswitch for DNA detection, gene transfection, and live-cell imaging.

Quantum dots (QDs) coated with an albumin-derived copolymer shell exhibit significant photoresponsiveness to DNA loading and have great potential for investigating gene delivery processes. The QDs reported herein are positively charged, have attractive optical properties, and are noncytotoxic and notably stable in live cells. Their complex formation with plasmid DNA leads to proportionally decreased photoluminescence and efficient gene transfection is observed.

Convenient approach to polypeptide copolymers derived from native proteins.

A convenient approach for the synthesis of narrowly dispersed polypeptide copolymers of defined compositions is presented. The controlled denaturation of the proteins serum albumin and lysozyme followed by an in situ stabilization with polyethylene(oxide) chains yields polypeptide side chain copolymers of precisely defined backbone lengths as well as the presence of secondary structure elements. Supramolecular architectures are formed in solution because of the presence of hydrophobic and hydrophilic amino acids along the polypeptide main chain.

Bioactive unnatural somatostatin analogues through bioorthogonal iodo- and ethynyl-disulfide intercalators.

Iodo- and ethynyl-containing bisalkylating bioconjugation agents 5 and 8 were achieved and allow the introduction of reactive unnatural substituents into proteins and peptides whilst the bioactive 3D structure is retained. Derivatives of the peptide hormone somatostatin bearing a single iodo or ethynyl group were prepared through intercalation into the disulfide bridge. For the first time, the exact reaction mechanism of the intercalation was elucidated by applying 2D NMR experiments and it was shown that, during the reaction, somatostatin diastereomers were formed.

Tailored Albumin-based Copolymers for Receptor-Mediated Delivery of Perylenediimide Guest Molecules.

The synthesis of a novel and multifunctional copolymer based on a human serum albumin backbone bearing several folic acid as well as PEO groups was presented. In solution, this side-chain copolymer adopts a globular architecture and about five molecules of the water-insoluble chromophore PDI were successfully incorporated into these micelles for receptor-mediated cell uptake investigations. A significant uptake of these bioconjugates via receptor-mediated endocytosis was detected for cells expressing folic acid receptors in the cell membrane.

Cationized albumin-biocoatings for the immobilization of lipid vesicles.

Tethered lipid membranes or immobilized lipid vesicles are frequently used as biomimetic systems. In this article, the authors presented a suitable method for efficient immobilization of lipid vesicles onto a broad range of surfaces, enabling analysis by quantitative methods even under rigid, mechanical conditions-bare surfaces such as hydrophilic glass surfaces as well as hydrophobic polymer slides or metal surfaces such as gold. The immobilization of vesicles was based on the electrostatic interaction of zwitterionic or negatively charged lipid vesicles with two types of cationic chemically modified bovine serum albumin (cBSA) blood plasma proteins (cBSA-113 and cBSA-147).

cBSA-147 for the preparation of bacterial biofilms in a microchannel reactor.

Whole cells are attractive biocatalysts, particularly if the reaction requires cofactors or involves multiple transformations. Immobilization of the catalyst is often a prerequisite for continuous processes. The highly cationic chemically modified plasma protein bovine serum albumin (cBSA-147) has been applied for the electrostatically mediated immobilization of the planktonic bacterium E.

Fine-tuning DNA/albumin polyelectrolyte interactions to produce the efficient transfection agent cBSA-147.

We present the preparation and isolation of different chemically modified BSA species with varying numbers of primary amino groups at the surface. Highly cationic albumin proteins with increased numbers of amino groups were achieved and complex formation with plasmid DNA was carefully investigated. We compare the transfection results, polyelectrolyte complexes morphologies with their impact on complex stabilities, cytotoxicities and DNA accessibility.

Phage release from biofilm and planktonic Staphylococcus aureus cells.

The ability of pathogenic staphylococci to form biofilms facilitates colonization and the development of chronic infections. Therapy is hampered by the high tolerance of biofilms towards antibiotic treatment and the immune system. We found evidence that lysogenic Staphylococcus aureus cells in a biofilm and in planktonic cultures spontaneously release phages into their surroundings.