6533b7defe1ef96bd1275efc

RESEARCH PRODUCT

HPMA-Based Nanoparticles for Fast, Bioorthogonal iEDDA Ligation

Barbara GräfenStefan KramerSascha SchmittLydia BraunKaloian KoynovDennis SvatunekRaffaella RossinArthur H. A. M. Van OnzenIrina AlbergHannes MikulaRudolf Zentel

subject

Polymers and PlasticsNanoparticleBioengineeringFluorescence correlation spectroscopy02 engineering and technologyConjugated system010402 general chemistry01 natural sciencesMicelleArticleBiomaterialsAmphiphileMaterials ChemistryCopolymerBenzene DerivativesColloidsMicellesPretargetingAza CompoundsCycloaddition ReactionChemistryOther Research Radboud Institute for Health Sciences [Radboudumc 0]021001 nanoscience & nanotechnologyCombinatorial chemistry0104 chemical sciencesCross-Linking ReagentsMethacrylatesNanoparticlesClick ChemistryBioorthogonal chemistry0210 nano-technology

description

Contains fulltext : 216143.pdf (Publisher’s version ) (Open Access) Fast and bioorthogonally reacting nanoparticles are attractive tools for biomedical applications such as tumor pretargeting. In this study, we designed an amphiphilic block copolymer system based on HPMA using different strategies to introduce the highly reactive click units 1,2,4,5-tetrazines (Tz) either at the chain end (Tz-CTA) or statistical into the hydrophobic block. This reactive group undergoes a rapid, bioorthogonal inverse electron-demand Diels-Alder reaction (iEDDA) with trans-cyclooctenes (TCO). Subsequently, this polymer platform was used for the preparation of different Tz-covered nanoparticles, such as micelles and colloids. Thereby it was found that the reactivity of the polymeric micelles is comparable to that of the low molar mass tetrazines. The core-cross-linked micelles can be successfully conjugated at rather low concentrations to large biomacromolecules like antibodies, not only in physiological buffer, but also in human blood plasma, which was confirmed by fluorescence correlation spectroscopy (FCS).

yearjournalcountryeditionlanguage
2019-01-01
10.1021/acs.biomac.9b00868http://hdl.handle.net/2066/216143