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Orthogonal Click Conjugation to the Liposomal Surface Reveals the Stability of the Lipid Anchorage as Crucial for Targeting
Author(s) -
Fritz Thomas,
Voigt Matthias,
Worm Matthias,
Negwer Inka,
Müller Sophie S.,
Kettenbach Kathrin,
Ross Tobias L.,
Roesch Frank,
Koynov Kaloian,
Frey Holger,
Helm Mark
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201602758
Subject(s) - liposome , click chemistry , chemistry , biophysics , nanotechnology , materials science , combinatorial chemistry , biology
Synthetic access to multiple surface decorations are a bottleneck in the development of liposomes for receptor mediated targeting. This opens a complex multiparameter space, exploration of which is severely limited in terms of sample numbers and turnaround times. Here, we unlock this technological barrier by a combination of a milligram‐scale liposome formulation using dual centrifugation and orthogonal click chemistry on the liposomal surface. Application of these techniques to conceptually new amphiphilic compounds, which feature norbornene and alkyne groups at the apex of sterically stabilizing, hyperbranched polyglycerol moieties, revealed a particular influence of the membrane anchor of functional amphiphiles. Folic acid residues clicked to cholesterol‐based amphiphiles were inefficient in folate‐mediated cell targeting, while dialkyl‐anchored amphiphiles remained stable in the liposomal membrane and imparted efficient targeting properties. These findings are of specific importance considering the popularity of cholesterol as a lipophilic anchor.