title: Combretastatin A-4 Conjugated Antiangiogenic Micellar Drug Delivery Systems Using Dendron-Polymer Conjugates.
abstract: Employment of polymeric nanomaterials in cancer therapeutics is actively pursued since they often enable drug administration with increased efficacy along with reduced toxic side effects. In this study, drug conjugated micellar constructs are fabricated using triblock dendron-linear polymer conjugates where a hydrophilic linear polyethylene glycol (PEG) chain is flanked by well-defined hydrophobic biodegradable polyester dendrons bearing an antiangiogenic drug, combretastatin-A4 (CA4). Variation in dendron generation is utilized to obtain a library of micellar constructs with varying sizes and drug loadings. In particular, a family of drug appended dendron-polymer conjugates based on polyester dendrons of generations ranging from G1 to G3 and 10 kDa linear PEG were obtained using [3 + 2] Huisgen type "click" chemistry. The final constructs benefit from PEG's hydrophilicity and antibiofouling character, as well as biodegradable nature of the hydrophobic polyester dendrons. The hydrophobic-hydrophilic-hydrophobic character of these constructs leads to the formation of flower-like micelles in aqueous media. In addition to generation-dependent subnanomolar range critical micelle concentrations, the resulting micelles possess hydrodynamic diameters suitable for passive tumor targeting through enhanced permeability and retention (EPR) effect; thereby they are suitable candidates as controlled drug delivery agents. For all constructs, in vitro cytotoxicities were investigated and inhibitory effect of Comb-G3-PEG on tube formation was shown on human umbilical vein endothelial cells (HUVECs).
authors.affiliation: Department of Chemistry, Bogazici University , Istanbul 34342, Turkey.
authors.forename: Burcu
authors.initials: B
authors.lastname: Sumer Bolu
authors.affiliation: Department of Chemistry, Bogazici University , Istanbul 34342, Turkey.
authors.forename: Ece
authors.initials: E
authors.lastname: Manavoglu Gecici
authors.affiliation: Department of Chemistry, Bogazici University , Istanbul 34342, Turkey.|Center for Life Sciences and Technologies, Bogazici University , Istanbul 34342, Turkey.
authors.forename: Rana
authors.initials: R
authors.lastname: Sanyal
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry*; D000873:Anthracenes / Q000737:chemistry*; D001632:Bibenzyls / Q000737:chemistry*; D002460:Cell Line; D016503:Drug Delivery Systems / Q000379:methods; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D049329:Nanostructures / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*
chemical_list: D020533:Angiogenesis Inhibitors; D000873:Anthracenes; D001632:Bibenzyls; D008823:Micelles; D011091:Polyesters; D011108:Polymers; C501244:dendron; D011092:Polyethylene Glycols; C040105:combretastatin
keywords: antiangiogenic; combretastatin-A4; flower micelle; micellar drug delivery; polyester dendron; “click” chemistry