Lysosome-targetable carbon dots for highly efficient photothermal/photodynamic synergistic cancer therapy and photoacoustic/two-photon excited fluorescence imaging

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT) holds great potential for efficient cancer therapy by inducing reactive oxygen species (ROS) or heat into tumor. Nevertheless, PDT or PTT suffers from some limitations, e.g., PTT requires long-time and high-power laser irradiation to generate enough heat, while the hypoxia microenvironment of tumor and the limit diffuse distance of ROS hamper the efficacy of oxygen-dependent PDT. Here we reported the carbon dots (CDs) which could simultaneously generate singlet oxygen (¹O₂), hydroxyl radical (OH[rad]), and heat under a 635 nm laser irradiation, with a ¹O₂ generation quantum yield of 5.7% and photothermal conversion efficiency of 73.5% (the highest thus far for CDs). Significantly, the CDs can selectively accumulate in lysosome, which is an ideal organelle for phototherapy because of its key role in sustaining cellular activity and stability. Moreover, the CDs present one-photon excited (OPE) and two-photon excited (TPE) fluorescence, and excellent photoacoustic (PA) imaging capability. Combining the good biocompatibility, the as-prepared CDs was served as multi-functional phototheranostic agent for synergistic PA/fluorescence imaging, and PDT/PTT.