bm9b00868_si_001.pdf (3.29 MB)
HPMA-Based Nanoparticles for Fast, Bioorthogonal iEDDA Ligation
journal contribution
posted on 2019-09-19, 13:42 authored by Stefan Kramer, Dennis Svatunek, Irina Alberg, Barbara Gräfen, Sascha Schmitt, Lydia Braun, Arthur H. A. M. van Onzen, Raffaella Rossin, Kaloian Koynov, Hannes Mikula, Rudolf ZentelFast
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).