Ruthenium-doped carbon dots with "three-in-one" chemodynamic, photodynamic, and photothermal activity induce panoptosis for tumor therapy

Combined nanocatalytic therapy has showed potential feasibility in cancer treatment. However, designing nanocatalytic particles with good biocompatibility, high catalytic activity, and precise targeted delivery remains a challenge. In this study, ingenious Ru-doped carbon dots (Ru-CDs) leveraging "three-in-one" photothermal, photodynamic, and chemodynamic modalities were synthesized without using additional photosensitizer or photothermal agent for synergistic tumor treatment. The Ru-CDs efficiently generated type I (hydroxyl radicals, & sdot;OH) and type II (singlet oxygen, 1O2) reactive oxygen species (ROS), which was rarely reported in Ru complexes. Subsequently, glucose oxidase (GOx) and hyaluronic acid (HA) were conjugated to Ru-CDs to construct Ru-CDsGOx@HA nanocomposites that had tumor cell targeting, starvation effects, as well as supplied the substrate (H2O2) for & sdot;OH. The photothermal, photodynamic, and chemodynamic activities of the CDs were markedly enhanced by Ru-doping. Furthermore, the immune adjuvants (cytosine-phosphate-guanine sequence, CpG) was conjugated to Ru-CDs-GOx@HA to produce an immunotherapeutic nanocomposite. Ru-CDs-GOx@HA inhibited the proliferation of cancer cells, and the inhibition further enhanced under near-infrared (NIR) radiation. RuCDs-GOx@HA suppressed tumor growth and metastasis and thus prolonged the survival of tumor-bearing nude mice under NIR irradiation. Interestingly, for the first time, we found that Ru-CDs-GOx@HA treatment elicited PANoptosis, including pyroptosis, apoptosis, necroptosis, and ferroptosis in cancer cells under NIR, which increased the immune response and potently prevented tumor metastasis, thus enhancing the therapeutic effect. This study highlighted Ru doping as an efficient approach for enhancing the chemodynamic, photodynamic, and photodynamic effects of CDs and therefore offered a promising strategy for efficient tumor therapy.