DNA-Targeting Bioactive Photosensitizer for Chemo-Photodynamic Therapy of Malignant Tumor

The design of a biologically active photosensitizer that effectively combines chemotherapy and photodynamic therapy remains a significant challenge. This article introduces a DNA targeted biologically active photosensitizer, CQA, which integrates the DNA alkylating moiety chlormethine with a photosensitizing moiety. Through DNA damage experiments and molecular docking, CQA has been demonstrated to act as an effective DNA targeting and damaging chemotherapeutic agent via chlormethine. Meanwhile, CQA can substantially amplify the DNA damage under light irradiation. Such enhancement is attributed to the introduction of the anthraquinone group, which possesses good redox properties and acts as an electron acceptor to promote electron transfer. Consequently, CQA efficiently generates both type-I and type-II reactive oxygen species (ROS), exerting an excellent photodynamic therapy (PDT) effect. The antitumor efficacy of CQA has been validated via results from in vivo tumor growth experiments, H&E staining, and IHC analyses. The design of this study emphasizes targeted DNA damage and enhanced ROS generation, underscoring the crucial role of efficient synergistic chemo- and photodynamic therapy in advancing cancer treatment strategies.