title: Dendronized albumin core-shell transporters with high drug loading capacity.
abstract: We describe the synthesis of a core-shell biohybrid consisting of a human serum albumin (HSA) core that serves as a reservoir for lipophilic molecules and a cationized shell region consisting of ethynyl-G2.0-PAMAM or ethynyl-G3.0-PAMAM dendrons. The binding capacity of lipophilic guests was quantified applying electron paramagnetic resonance (EPR) spectroscopy, and five to six out of seven pockets were still available compared with HSA. The attachment of ethynyl-G2.0-PAMAM dendrons to HSA yielded a nontoxic core-shell macromolecule that was clearly uptaken by A549 human epithelial cells due to the presence of the dendritic PAMAM shell. Significantly higher loading of doxorubicin was observed for dendronized G2-DHSA compared with the native protein due to the availability of binding pockets of the HSA core, and interaction with the dendritic shell. Dendronized G2-DHSA-doxorubicin displayed significant cytotoxicity resulting from high drug loading and high stability under different conditions, thus demonstrating its great potential as a transporter for drug molecules.
authors.affiliation: Institute of Organic Chemistry III, University of Ulm, Albert-Einstein-Allee 11, Ulm, Germany.
authors.forename: Seah Ling
authors.initials: SL
authors.lastname: Kuan
authors.forename: Bettina
authors.initials: B
authors.lastname: Stöckle
authors.forename: Jörg
authors.initials: J
authors.lastname: Reichenwallner
authors.forename: David Y W
authors.initials: DY
authors.lastname: Ng
authors.forename: Yuzhou
authors.initials: Y
authors.lastname: Wu
authors.forename: Mikheil
authors.initials: M
authors.lastname: Doroshenko
authors.forename: Kaloian
authors.initials: K
authors.lastname: Koynov
authors.forename: Dariush
authors.initials: D
authors.lastname: Hinderberger
authors.forename: Klaus
authors.initials: K
authors.lastname: Müllen
authors.forename: Tanja
authors.initials: T
authors.lastname: Weil
mesh_terms: D002277:Carcinoma / Q000188:drug therapy; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D053179:Caspase 7 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D050091:Dendrimers / Q000737:chemistry* / Q000378:metabolism*; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004578:Electron Spin Resonance Spectroscopy; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D012709:Serum Albumin / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; D012709:Serum Albumin; D004317:Doxorubicin; D053148:Caspase 3; D053179:Caspase 7