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(-isopropylacrylamide) unit, a metal ion-recognizing benzo-18-crown-6-acrylamide unit, and a photoluminescent fluorescein -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.