Development of a Potassium-Ion-Responsive Star Copolymer with Controlled Aggregation/Dispersion Transition

Stimuli-responsive star polymers are promising functional materials whose aggregation, adhesion, and interaction with cells can be altered by applying suitable stimuli. Among several stimuli assessed, the potassium ion (K⁺), which is known to be captured by crown ethers, is of considerable interest because of the role it plays in the body. In this study, a K⁺-responsive star copolymer was developed using a polyglycerol (PG) core and grafted copolymer arms consisting of a thermo-responsive poly(N-isopropylacrylamide) unit, a metal ion-recognizing benzo-18-crown-6-acrylamide unit, and a photoluminescent fluorescein O-methacrylate unit. Via optimization of grafting density and copolymerization ratio of grafted arms, along with the use of hydrophilic hyperbranched core, microsized aggregates with a diameter of 5.5 μm were successfully formed in the absence of K⁺ ions without inducing severe sedimentation (the lower critical solution temperature (LCST) was 35.6 °C). In the presence of K⁺ ions, these aggregates dispersed due to the shift in LCST (47.2 °C at 160 mM K⁺), which further induced the activation of fluorescence that was quenched in the aggregated state. Furthermore, macrophage targeting based on the micron-sized aggregation state and subsequent fluorescence activation of the developed star copolymers in response to an increase in intracellular K⁺ concentration were performed as a potential K⁺ probe or K⁺-responsive drug delivery vehicle.