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White-light-driven fluorescence switch for super-resolution imaging guided photodynamic and photoacid therapy

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Abstract

Photocaged fluorophores with photoactivatable characteristics presented important applications in imaging the biological structures and processes. Taking advantage of their super-resolution imaging merits to manipulate and visualize anti-cancer treatment is always a goal of modern clinical medicine. Traditional photodynamic therapy (PDT) is a noninvasive treatment but limited in intracellular oxygen content. Type I PDT and photoacid therapy (PAT) are two effective supplements of traditional PDT especially in hypoxic condition. Herein, a novel white-light-driven fluorescence switch (7H-dibenzo[c,g]carbazol-7-yl)(2-iodophenyl)methanone (2IB) was designed and synthesized as an unprecedent “all in one” platform for stochastic optical reconstruction microscopy (STORM) imaging guided Type I/II PDT and PAT. The experimental and theoretical studies revealed that the working mechanism is based on two competing paths under excitation: photosensitization and photocyclization reaction. Efficient intersystem crossing (ISC) ensured the generation of reactive oxygen species (ROS) for PDT, while low energy barrier facilitated the photocyclization reaction that simultaneously yielded emissive fluorophores (2IBC) and H+ for super-resolution imaging and photoacid, respectively. Impressively, the fluorescent intensity of mitochondria-targeted 2IBC was positively correlated with treatment efficacy, which is beneficial to spatiotemporally visualized therapeutic process and outcome. As a result, superior anti-tumor performance was achieved in vitro and in vivo. This contribution provided a multifunctional nanodrug paradigm for multimode cancer diagnosis and treatment.

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Acknowledgements

This work was supported by the Beijing Natural Science Foundation (Z210017), the National Natural Science Foundation of China (21774130, 51925306), the National Key R&D Program of China (2018FYA 0305800), the Key Research Program of Frontier Sciences, Chinese Academy of Sciences (QYZDB-SSW-JSC046), the Strategic Priority Research Program, Chinese Academy of Sciences (XDB28000000) and University of Chinese Academy of Sciences. DFT results described in this communication are obtained on the National Supercomputing Center in Shenzhen (Shenzhen Cloud Computing Center). The animal experiments were performed in accordance with the animal use and care regulations of the Fifth Affiliated Hospital, Sun Yat-sen University (00216).

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Correspondence to Kaikai Wen, Qian Peng or Hui Huang.

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Conflict of interest The authors declare no conflict of interest.

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Supporting information The supporting information is available online at https://chem.scichina.com and https://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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Chen, H., Wen, K., Lu, Y. et al. White-light-driven fluorescence switch for super-resolution imaging guided photodynamic and photoacid therapy. Sci. China Chem. 65, 2528–2537 (2022). https://doi.org/10.1007/s11426-022-1369-9

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  • DOI: https://doi.org/10.1007/s11426-022-1369-9

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