1. Win-win integration: A mitochondria targeted AIE photosensitizer for hypochlorite detection and type I & type II photodynamic therapy.
- Author
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Ni, Jiahao, Yu, Lichao, Wang, Yixuan, Yang, Tong, Bai, Yueqi, Zheng, Bowen, Liang, Manshan, Ye, Xiaoxia, Quan, Yun-Yun, Lin, Feifei, and Huang, Zu-Sheng
- Subjects
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PHOTODYNAMIC therapy , *REACTIVE oxygen species , *NONINVASIVE diagnostic tests , *TUMOR microenvironment , *PHOTOSENSITIZERS - Abstract
Photodynamic therapy (PDT) is a pioneering and effective anticancer modality with low adverse effects and high selectivity. Hypochlorous acid or hypochlorite (HClO/ClO−) is a type of inflammatory cytokine. The abnormal increase of ClO− in tumor cells is related to tumor pathogenesis and may be a "friend" for the design and synthesis of responsive phototherapy agents. However, preparing responsive phototherapy agents for all-in-one noninvasive diagnosis and simultaneous in situ therapy in a complex tumor environment is highly desirable but still remains an enormously demanding task. An acceptor-π bridge-donor-π bridge-acceptor (A-π-D-π-A) type photosensitizer TPTPy was designed and synthesized based on the phenothiazine structure which was used as the donor moiety as well as a ClO− responsive group. TPTPy was a multifunctional mitochondria targeted aggregation-induced emission (AIE) photosensitizer which could quickly and sensitively respond to ClO− with fluorescence "turn on" performance (19-fold fluorescence enhancement) and enhanced type I reactive oxygen species (ROS) generation to effectively ablate hypoxic tumor cells. The detection limit of TPTPy to ClO− was calculated to be 185.38 nM. The well-tailored TPTPy anchoring to mitochondria and producing ROS in situ could disrupt mitochondria and promote cell apoptosis. TPTPy was able to image inflammatory cells and tumor cells through ClO− response. In vivo results revealed that TPTPy was successfully utilized for PDT in tumor bearing nude mice and exhibited excellent biological safety for major organs. A win-win integration strategy was proposed to design a tumor intracellular ClO− responsive photosensitizer TPTPy capable of both type I and type II ROS production to achieve photodynamic therapy of tumor. This work sheds light on the win-win integration design by taking full advantage of the characteristics of tumor microenvironment to build up responsive photosensitizer for in situ PDT of tumor. [Display omitted] • An AIE photosensitizer TPTPy for ClO− detection and follow-on PDT is designed. • TPTPy can target mitochondria and generate type I and type II ROS for PDT. • TPTPy can detect ClO− with fluorescence turn on and enhanced type I ROS generation. • TPTPy can detect endogenous ClO− in inflammatory cells and tumor cells. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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