title: Click modification of multifunctional liposomes bearing hyperbranched polyether chains.
abstract: Aiming at controlled modification of liposomal surface structures, we describe a postpreparational approach for surface derivatization of a new type of multifunctional, sterically stabilized liposomes. Application of dual centrifugation (DC) resulted in high encapsulation efficiencies above 50% at very small batch sizes with a total volume of 150 μL, which were conductive to fast and efficient optimization of variegated surface modification reactions. Cholesterol-polymer amphiphiles, including complex hyperbranched polyether structures bearing 1-4 terminal alkynes, were used in DC formulations to provide steric stabilization. The alkyne moieties were explored as anchors for the conjugation of small molecules to the liposomal surface via click chemistry, binding 350-450 fluorophores per liposome as examples for surface active molecules. Using Förster resonance energy transfer (FRET) spectroscopy, the conjugation reaction as well as the uptake of FRET-labeled liposomes by RBE4 cells was monitored, and the distribution of the fluorescent lipids among cellular structures and membranes could be studied. Thus, the combination of clickable hyperbranched amphiphiles and dual centrifugation provides access to well-defined liposomal formulations with a variety of surface moieties.
authors.affiliation: Institute of Pharmacy and Biochemistry, Johannes Gutenberg-University Mainz , Staudingerweg 5, 55122 Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fritz
authors.forename: Markus
authors.initials: M
authors.lastname: Hirsch
authors.forename: Felix C
authors.initials: FC
authors.lastname: Richter
authors.forename: Sophie S
authors.initials: SS
authors.lastname: Müller
authors.forename: Anna M
authors.initials: AM
authors.lastname: Hofmann
authors.forename: Kristiane A K
authors.initials: KA
authors.lastname: Rusitzka
authors.forename: Jürgen
authors.initials: J
authors.lastname: Markl
authors.forename: Ulrich
authors.initials: U
authors.lastname: Massing
authors.forename: Holger
authors.initials: H
authors.lastname: Frey
authors.forename: Mark
authors.initials: M
authors.lastname: Helm
mesh_terms: D000480:Alkynes / Q000737:chemistry; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D057930:Click Chemistry; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D008081:Liposomes; D018613:Microscopy, Confocal; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats
chemical_list: D000480:Alkynes; D008081:Liposomes; D011108:Polymers; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin