posted on 2024-02-15, 18:11authored byYu Tian, Li Wang, Yunyun Qian, Ling Li, Hao Li, Xuejiao Song, Minjia Wang, Najia Zhu, Yao Tong, Wenbo Wu, Leilei Shi
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.