Affinity Induced Surface Functionalization of Liposomes Using Cu-Free Click Chemistry

Martin Bak, Rasmus Irming Jølck, Rasmus Eliasen, Thomas Lars Andresen

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Abstract

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.
Original languageEnglish
JournalBioconjugate Chemistry
Volume27
Issue number7
Pages (from-to)1673-80
ISSN1043-1802
DOIs
Publication statusPublished - 2016

Cite this

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title = "Affinity Induced Surface Functionalization of Liposomes Using Cu-Free Click Chemistry",
abstract = "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.",
author = "Martin Bak and J{\o}lck, {Rasmus Irming} and Rasmus Eliasen and Andresen, {Thomas Lars}",
year = "2016",
doi = "10.1021/acs.bioconjchem.6b00221",
language = "English",
volume = "27",
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journal = "Bioconjugate Chemistry",
issn = "1043-1802",
publisher = "American Chemical Society",
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Affinity Induced Surface Functionalization of Liposomes Using Cu-Free Click Chemistry. / Bak, Martin; Jølck, Rasmus Irming; Eliasen, Rasmus; Andresen, Thomas Lars.

In: Bioconjugate Chemistry, Vol. 27, No. 7, 2016, p. 1673-80.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Affinity Induced Surface Functionalization of Liposomes Using Cu-Free Click Chemistry

AU - Bak, Martin

AU - Jølck, Rasmus Irming

AU - Eliasen, Rasmus

AU - Andresen, Thomas Lars

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

U2 - 10.1021/acs.bioconjchem.6b00221

DO - 10.1021/acs.bioconjchem.6b00221

M3 - Journal article

C2 - 27269516

VL - 27

SP - 1673

EP - 1680

JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

SN - 1043-1802

IS - 7

ER -