Cationic Water-Soluble Pillar[5]arene-Modified Cu2–xSe Nanoparticles: Supramolecular Trap for ATP and Application in Targeted Photothermal Therapy in the NIR-II Window

With the rapid progress of nanotechnology, near-infrared (NIR), light-assisted phototherapy as a minimally invasive local cancer therapy, especially photothermal therapy (PTT), has captured broad research attention in recent years. However, combined target molecules with a PTT system through reversible supramolecular interactions has been reported rarely. In this work, we constructed a supramolecular nanosystem combining ATP capture and target PTT based on cationic pillar[5]arene (CWP5)-functionalized Cu2–xSe nanoparticles (Cu2–xSe@CWP5 NPs). Cu2–xSe@CWP5 NPs, with an average diameter of approximately 100 nm and strong absorption in the near-infrared-II window, were prepared in water through a facile one-step in situ synthesis method, then (4-carboxybutyl)triphenylphosphonium bromide (TPP), a mitochondria-targeted molecule, was modified on the surface of the particles through the host–guest recognition. Upon irradiation with a 1064 nm laser, the obtained Cu2–xSe@CWP5/TPP NPs showed remarkably photothermal ablation capability to HeLa cells. Importantly, our Cu2–xSe@CWP5/TPP NPs exhibited excellent therapeutic effect due to the combination of inhibited hydrolysis of ATP and targeted photothermal therapy upon in vitro and in vivo studies. Significantly, through host–guest interactions, we can modify different types of target molecules within this PTT system at will