Self-Quenched Metal–Organic Particles as Dual-Mode Therapeutic Agents for Photoacoustic Imaging-Guided Second Near-Infrared Window Photochemotherapy

The nanosized metal–organic particles (NMOPs) recently have attracted tremendous attentions in biomedical applications. However, few studies have developed metal–organic nanoparticles (NMOPs) as near-infrared (NIR) II phototherapeutic agents and as Fenton-like agents for cancer theranostics. Herein, directly using organic dye and Cu(II)-ion complexes to construct NMOPs, as dual-mode therapeutic agent for PA imaging-guided photochemotherapy in NIR II window, is reported. The NMOPs are simply an assembly of Cu(II) ion and tetrahydroxyanthraquinone (THQ) complexes [Cu(II)–THQ]n through the coordination effect, van der Waals force, and π–π interactions. After modification of polyethylene glycol (PEG–(NH2)2), the obtained Cu–THQNPs endow excellent biocompatibility and stability in physiological conditions. Because of the strong absorption at NIR II window and photoinduced electrontransfer (PET) mechanism, the Cu–THQNPs not only acted as an excellent photothermal agent with extremely high light-to-heat conversion ability (51.34%) at 1064 nm for phototherapy but also explored as the PA contrast agent for precisely tracking and guiding the therapy in vivo. Most strikingly, our Cu–THQNPs can be degraded by tumor-specific acidic-cleaving of the coordination bonds and follow by the slow release of Cu(II) into tumors, which can act as Fenton-like agents to generate •OH from H2O2 for enhancing the antitumor efficacy in vivo. With almost 100% prevention of the tumor growth for ca. 14 days and no obvious toxicity based on blood biochemical/histological analysis, this work highlights the Cu–THQNPs as an efficient NIR II therapeutic agent for precise cancer theranostics.