Affinity Induced Surface Functionalization of Liposomes Using Cu-Free Click Chemistry.
Functionalization of nanoparticles is a key element for improving specificity of drug delivery systems toward diseased tissue or cells. In the current study we report a highly efficient and chemoselective method for post-functionalization of liposomes with biomacromolecules, which equally well can be used for functionalization of other nanoparticles or solid surfaces. The method exploits a synergistic effect of having both affinity and covalent anchoring tags on the surface of the liposome. This was achieved by synthesizing a peptide linker system that uses Cu-free strain-promoted click chemistry in combination with histidine affinity tags. The investigation of post-functionalization of PEGylated liposomes was performed with a cyclic RGDfE peptide. By exploring both affinity and covalent tags a 98 ± 2.0% coupling efficiency was achieved, even a diluted system showed a coupling efficiency of 87 ± 0.2%. The reaction kinetics and overall yield were quantified by HPLC. The results presented here open new possibilities for constructing complex nanostructures and functionalized surfaces.
Department of Micro- and Nanotechnology, DTU Nanotech, Center for Nanomedicine and Theranostics, Technical University of Denmark , Building 423, Lyngby DK-2800, Denmark.
Martin
M
Bak
Department of Micro- and Nanotechnology, DTU Nanotech, Center for Nanomedicine and Theranostics, Technical University of Denmark , Building 423, Lyngby DK-2800, Denmark.
Rasmus I
RI
Jølck
Department of Micro- and Nanotechnology, DTU Nanotech, Center for Nanomedicine and Theranostics, Technical University of Denmark , Building 423, Lyngby DK-2800, Denmark.
Rasmus
R
Eliasen
Department of Micro- and Nanotechnology, DTU Nanotech, Center for Nanomedicine and Theranostics, Technical University of Denmark , Building 423, Lyngby DK-2800, Denmark.
Thomas L
TL
Andresen
D000480:Alkynes / Q000737:chemistry; D057930:Click Chemistry; D008081:Liposomes / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009571:Nitrilotriacetic Acid / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D013499:Surface Properties
D000480:Alkynes; D008081:Liposomes; D011092:Polyethylene Glycols; D009571:Nitrilotriacetic Acid