Poly(ionic liquid)-Gated CuCo₂S₄ for pH-/Thermo-Triggered Drug Release and Photoacoustic Imaging

A novel hybrid drug nanocarrier is developed with CuCo2S4 nanoparticles as the core to be encapsulated by poly(ionic liquid) (PIL), that is, poly(tetrabutylphosphonium styrenesulfonate) (P[P4,4,4,4][SS]), as the shell. Doxorubicin (DOX) is loaded onto the PIL shell via electrostatic attraction involving amine in DOX and styrenesulfonate in PIL. pH- and thermal-responsive characteristics of P[P4,4,4,4][SS] endow the multifunctional hybrid nanocarrier system DOX–CuCo2S4@PIL with sensitive dual-stimuli-triggered drug release behaviors. The CuCo2S4 core converts near-infrared (NIR) irradiation into thermal energy to trigger the shrinkage of the PIL shell, which subsequently promotes drug release, and the pH-responsive release of DOX involves pH-sensitive electrostatic interaction of the PIL shell with DOX. A favorable controlled release of 90.5% is achieved under pH/thermo dual stimuli. In vitro experiments with MCF-7 cells well demonstrated that the drug release is controlled by the acidic intracellular environment with NIR irradiation. The CuCo2S4 core also serves as a photoacoustic (PA) imaging contrast agent, as demonstrated by in vivo treatment of the MCF-7-carrying mice.