Lysosomal‐Targeting and Light/Ultrasound Sensitive Carbon Dots for Combined Photodynamic and Sonodynamic Therapies of Breast Tumor

Abstract The combination of photodynamic therapy (PDT) with sonodynamic therapy (SDT) can compensate for shortcomings of PDT, such as the limited tissue penetration depth or low efficiency of reactive oxygen species (ROS) generation of SDT, but it is still a great challenge to design and synthesize an ideal photo‐/sono‐sensitizer with a satisfactory targeting capability and biosafety. Herein, a novel type of carbon dots (CDs) containing morpholino surface group and the photo‐/sono‐sensitive core is synthesized by using levofloxacin and methylene blue as precursors via a hydrothermal synthesis. The as‐synthesized CDs show a highly efficient generation of singlet oxygen ( 1 O 2 ) under a red laser irradiation while producing 1 O 2 and hydroxyl radical (·OH) under a low‐intensity pulsed US stimulation, which leads to a remarkably enhanced ROS production yield in combined PDT and SDT of breast tumor. In the meantime, the CDs demonstrate a lysosome‐targeting ability in breast tumor cells, which causes lysosomal damage and release of acid phosphatase, resulting in massive apoptosis of cells and more than 90% of cell death. Further, in vivo experimental results confirm the effect of the CDs to inhibit or even eliminate the tumor growth of 4T1 tumor‐bearing mice after the combined PDT and SDT.