Design and Synthesis of Core-Shell Microgels with One-Step Clickable Crosslinked Cores and Ultralow Crosslinked Shells

The present study is conducted to explore the engineering of core-shell microgels such that the core can be rapidly labeled with a variety of fluorophores, while the shell retains the softness needed in specific biomedical applications. Azide containing crosslinked core particles based on a crosslinked poly(N-isopropylacrylamide) particle, using a one-pot, multistep polymerization is synthesized. A core-shell microgel is then synthesized by growing a crosslinker-free poly(N-isopropylacrylamide)-co-acrylic acid (ULC10AAc) shell through a two-step seed and feed polymerization. A simple click reaction between the azide present on the core and dibenzocyclooctyne containing fluorophores to make dyed core-shell microgels is further demonstrated. This approach toward dyed core-shell microgels eliminates the difficulty of crossreactivity between shell-localized chemoligation sites and the core-localized functionalities. The use of strained-ring systems to achieve the click reaction eliminates the use of cytotoxic catalysts common in traditional click chemistry. This approach allows not only to label the microgel core with different fluorophores but also to synthesize multiprobe core-shell microgel by simultaneously labeling a microgel core with multiple different fluorophores.