K⁺ -Responsive Block Copolymer Micelles for Targeted Intracellular Drug Delivery

In this work, a novel type of block copolymer micelles with K⁺ -responsive characteristics for targeted intracellular drug delivery is developed. The proposed smart micelles are prepared by self-assembly of poly(ethylene glycol)-b-poly(N-isopropylacry-lamide-co-benzo-18-crown-6-acrylamide) (PEG-b-P(NIPAM-co-B18C6Am)) block copolymers. Prednisolone acetate (PA) is successfully loaded into the micelles as the model drug, with loading content of 4.7 wt%. The PA-loaded micelles display a significantly boosted drug release in simulated intracellular fluid with a high K⁺ concentration of 150 × 10^-3 m, as compared with that in simulated extracellular fluid. Moreover, the in vitro cell experiments indicate that the fluorescent molecules encapsulated in the micelles can be delivered and specifically released inside the HSC-T6 and HepG2 cells responding to the increase of K⁺ concentration in intracellular compartments, which confirms the successful endocytosis and efficient K⁺ -induced intracellular release. Such K⁺ -responsive block copolymer micelles are highly potential as new-generation of smart nanocarriers for targeted intracellular delivery of drugs.