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Dendronized Albumin Biohybrids as Efficient Core-Shell Delivery Systems.


Biomacromolecules. 2012 Dec 4;


Authors: Kuan SL, Stoeckle B, Reichenwallner J, Ng DY, Wu Y, Doroshenko M, Koynov K, Hinderberger D, Mullen K, Weil T


Abstract

Nanocarriers which can facilitate cell uptake are highly attractive for therapeutic purposes. We describe the synthesis of a core-shell biohybrid consisting of a human serum albumin (HSA) core that serves as a reservoir for hydrophobic drugs and a cationized shell region consisting of ethynyl-G2.0-PAMAM and ethynyl-G3.0-PAMAM dendrons as candidates for drug delivery. The binding capacity of lipohilic guest molecules was quantified applying Electron Paramagnetic Resonance (EPR) Spectroscopy and pronounced differences compared to cationic HSA derivatives were observed. The attachment of ethynyl-G2.0-PAMAM dendrons to HSA yielded non-toxic macromolecules that are clearly uptaken by A549 human epithelial cell lines. Higher loading of doxorubicin was observed for dendronized G2-HSA compared to the native protein. The IC50 values at 24 and 48 hr for the dendronized G2-HSA -doxorubicin construct were determined to be in the micro- and submicro-molar range, thus demonstrating its efficiency as a carrier for the anticancer drug, doxorubicin.

PMID: 23210662 [PubMed - as supplied by publisher]