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Background: 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., Results: 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., Significance and Novelty: 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cancer as a leading cause of premature death worldwide has become a major threat to human health due to the high incidence and mortality. Monitoring tumor markers are reliable and significantly important for early detection of cancers. In complex biological systems, it is of great urgency but still remains challenging to conceive a fluorescent probe with multiple tumor markers detection property. Hydrogen sulfide (H 2 S) and pH are two target biomarkers for diagnosis of early cancer. The preparation of a novel probe with H 2 S and pH dual detection functions is highly anticipated., Results: Herein, a novel sequential detection probe HTPQ-HS for H 2 S and pH has been developed. In this system, HPQ (2-(2 -hydroxyphenyl)-4(3H)-quinazolinone) structure combined with triphenylamine is applied as the fluorophore, and 2, 4-dinitrophenylsulfonyl group is used as the recognition group. In the presence of H 2 S, HTPQ-HS is transformed into product HTPQ-OH which shows fluorescence enhancement (29-fold) at 525 nm in less than 4 min and further displays repeatable acid-base responsive ability. HTPQ-HS is able to sequentially response to H 2 S and pH in living cells and does not react directly with pH. Owing to the low cytotoxicity, HTPQ-HS is able to detect exogenous and endogenous H 2 S in colon cancer cells and mice, monitor H 2 S in inflammation model and in foodstuffs. As the environment changes from acidic to alkaline, the fluorescence intensity ratio (I 470 /I 530 ) of product HTPQ-OH changes remarkably, illustrating the ratiometric fluorescent responsiveness to pH., Significance and Novelty: A multifunctional fluorescent probe HTPQ-HS for sequential detection of H 2 S and pH is synthesized. Probe HTPQ-OH realizes the monitoring of dynamic changes in intracellular pH and displays prospective application in security printing. We expect that our work could offer an important guidance on the development of multifunctional fluorescent probes for visualizing H 2 S and pH in biology and environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)