Cu₂Se-Based Thermoresponsive Multifunctional Nanomaterial Initiated by NIR-II Light for Cancer Therapy

There is an urgent need to explore photothermal conversion agents and more effective treatment methods that are sensitive to the second near-infrared window. Based on this, we designed a more comprehensive treatment system combining photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy ingeniously, which is quite innovative and promising for treating tumors, especially in hypoxic environments. The Cu2Se-based nanoplatform was constructed and controlled by the coating of a mesoporous SiO2 shell, and the large mesoporous structure was then filled with DOX which exhibits dual responses to changes in pH and NIR-II. When irradiated by a 1064 nm laser, the photothermal agent of Cu2Se plays an important role in initiating the switch in the whole nanoplatform whose hyperthermia not only realized fundamental PTT but also converted H2O2 into biotoxic reactive oxygen species (ROS) such as ·OH, ·O2– through intracellular Cu+/Cu2+ circulating response. Besides, the encapsulation of the drug doxorubicin (DOX) in mesoporous SiO2 prevents early drug leakage. High permeability and retention of the tumor site allow nanoparticles to accumulate and be engulfed by cells, and DOX will be rapidly released due to a decrease in pH in the tumor environment. As expected, cell experiment in vitro and mice experiment in vivo further assessed the excellent biocompatibility and antitumor effects, indicating that the nanoplatform of Cu2Se@mSiO2-PEG-DOX showed promise for simultaneous treatment in hypoxic cancer therapy.