Orthogonal Click Conjugation to the Liposomal Surface Reveals the Stability of the Lipid Anchorage as Crucial for Targeting
| Autor: | Thomas Fritz, Matthias Worm, Mark Helm, Sophie S. Müller, Holger Frey, Frank Roesch, Tobias L. Ross, Inka Negwer, Matthias Voigt, Kaloian Koynov, Kathrin Kettenbach |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Glycerol
Polymers Stereochemistry Alkyne 02 engineering and technology 010402 general chemistry 01 natural sciences Catalysis Folic Acid Amphiphile Humans chemistry.chemical_classification Liposome Organic Chemistry General Chemistry Receptor-mediated endocytosis 021001 nanoscience & nanotechnology Lipids 0104 chemical sciences Cholesterol Membrane Folic acid chemistry Liposomes Drug delivery Click chemistry Biophysics Click Chemistry 0210 nano-technology |
| Zdroj: | Chemistry - A European Journal. 22:11578-11582 |
| ISSN: | 0947-6539 |
| DOI: | 10.1002/chem.201602758 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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