Diketopyrrolopyrrole-Based Photosensitizers Conjugated with Chemotherapeutic Agents for Multimodal Tumor Therapy

For synergistic cancer therapy, it is highly desirable to devise a single multifunctional agent to combine photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy, which is soluble and excitable at low irradiation, as well as able to selectively target tumors and achieve high efficacy. Toward this ambition, here the chemotherapy drugs chlorambucil (Cb), and all trans retinoic acid (ATRA) are covalently conjugated onto a small dye molecule diketopyrrolopyrrole (DPP-Cb and DPP-ATRA). The soluble nanoparticles (NPs) of DPP-Cb and DPP-ATRA formed by reprecipitation can selectively accumulate in tumors, release chemotherapy drugs under acidic conditions, and exhibit efficient reactive oxygen species (ROS) generation and photothermal conversion under the irradiation of a low power xenon lamp (40 mW/cm²). We show in vitro and in vivo that both NPs can effectively kill cancer cells and suppress cancer growth at a low dose (0.4 mg/kg).