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Wu Y.,Institute of Organic Chemistry III
Biointerphases | Year: 2012

We present the discovery of a nano-sized protein-derived micellar drug delivery system based on the polycationic albumin precursor protein cBSA-147. The anticancer drug doxorubicin (DOX) was efficiently encapsulated into nanosized micelles based on hydrophobic interactions with the polypeptide scaffold. These micelles revealed attractive stabilities in various physiological buffers and a wide pH range as well as very efficient uptake into A549 cells after 1 h incubation time only. In vitro cytotoxicity was five-times increased compared to free DOX also indicating efficient intracellular drug release. In addition, multiple functional groups are available for further chemical modifications. Based on the hydrophobic loading mechanism, various classical anti-cancer drugs, in principle, could be delivered even synergistically in a single micelle. Considering these aspects, this denatured albumin-based drug delivery system represents a highly attractive platform for nanomedicine approaches towards cancer therapy. Source


Wu Y.,Institute of Organic Chemistry III | Wu Y.,National University of Singapore | Shih E.K.,National University of Singapore | Ramanathan A.,National University of Singapore | And 3 more authors.
Biointerphases | Year: 2012

We present the discovery of a nano-sized protein- derived micellar drug delivery system based on the polycationic albumin precursor protein cBSA-147. The anticancer drug doxorubicin (DOX) was efficiently encapsulated into nanosized micelles based on hydrophobic interactions with the polypeptide scaffold. These micelles revealed attractive stabilities in various physiological buffers and a wide pH range as well as very efficient uptake into A549 cells after 1 h incubation time only. In vitro cytotoxicity was five-times increased compared to free DOX also indicating efficient intracellular drug release. In addition, multiple functional groups are available for further chemical modifications. Based on the hydrophobic loading mechanism, various classical anti-cancer drugs, in principle, could be delivered even synergistically in a single micelle. Considering these aspects, this denatured albumin-based drug delivery system represents a highly attractive platform for nanomedicine approaches towards cancer therapy. © The Author(s) 2012. Source


Wu Y.,Institute of Organic Chemistry III | Wu Y.,Max Planck Institute for Polymer Research | Ihme S.,Institute of Experimental Cancer Research | Feuring-Buske M.,Institute of Experimental Cancer Research | And 8 more authors.
Advanced Healthcare Materials | Year: 2013

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. 28 DOX molecules were covalently conjugated to the albumin polypeptide backbone via an acid sensitive hydrazone linker. Polycationic and pegylated human serum albumin formed two non-toxic and enzymatically degradable protection shells around the encapsulated DOX molecules. This core-shell delivery system possesses notable advantages, including a high drug loading capacity critical for low administration doses, a two-step drug release mechanism based on pH and the presence of proteases, an attractive biocompatibility and narrow size distribution inherited from the albumin backbone, as well as fast cellular uptake and masking of epitopes due to a high degree of pegylation. The IC50 of these nanoscopic onion-type micelles was found in the low nanomolar range for Hela cells as well as leukemia cell lines. In vivo data indicate its attractive potential as anti-leukemia treatment suggesting its promising profile as nanomedicine drug delivery system. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Wu Y.,Institute of Organic Chemistry III | Ng D.Y.W.,Institute of Organic Chemistry III | Kuan S.L.,Institute of Organic Chemistry III | Weil T.,Institute of Organic Chemistry III
Biomaterials Science | Year: 2015

The development of protein-polymer hybrids emerged several decades ago with the vision that their synergistic combination will offer macromolecular hybrids with manifold features to succeed as the next generation therapeutics. From the first generation of protein-polymer therapeutics represented by PEGylated proteins, the field has since advanced, reinforced by the progress in contemporary chemical techniques for designing polymeric scaffolds and protein engineering. Novel polymerization techniques that offer multifunctional strategies as well as a greater understanding of proteins and their biological behavior have both proven to be exceptional tools in the construction of these hybrid materials. In this review, we seek to summarize and highlight the recent progress in these semi-synthetic protein hybrids in terms of their preparation, design, resulting bioarchitectures and bioactivities for their intended bio-applications. © The Royal Society of Chemistry 2015. Source


Wu Y.,Institute of Organic Chemistry III | Eisele K.,Institute of Organic Chemistry III | Doroshenko M.,Max Planck Institute for Polymer Research | Algara-Siller G.,University of Ulm | And 4 more authors.
Small | Year: 2012

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. Therefore, they are suitable for live-cell bioimaging and mechanistic studies of nonviral gene delivery. Fluorescence correlation spectroscopy is applied for the first time to investigate individual QDs diffusing in large endosomes inside living cells, and serves as a valuable tool to study the physical properties of QDs inside live cells. The data obtained in this study strongly support the notable stability of these QDs, even in cell endosomes. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

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