All-in-one mitochondria-targeted NIR-II fluorophores for cancer therapy and imaging |
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| Authors: | Yujia Zheng Qianqian Li Jing Wu Ziyi Luo Wenyi Zhou Anguo Li Yanling Chen Tuerxunayi Rouzi Tian Tian Hui Zhou Xiaodong Zeng Yang Li Xiaoding Cheng Yongchang Wei Zixin Deng Fuling Zhou Xuechuan Hong |
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| Affiliation: | Department of Hematology, Zhongnan Hospital of Wuhan University, State Key Laboratory of Virology, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071 China.; College of Science, Innovation Center for Traditional Tibetan Medicine Modernization and Quality Control, Tibet University, Lhasa 850000 China ; Department of Radiation Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071 China ; Shenzhen Institute of Wuhan University, Shenzhen 518057 China |
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| Abstract: | Small-molecule subcellular organelle-targeting theranostic probes are crucial for early disease diagnosis and treatment. The imaging window of these molecules is mainly focused on the visible and near-infrared region (below ∼900 nm) which limits the tissue penetration depth and therapeutic effects. Herein, a novel NIR-II small-molecule probe H4–PEG-Glu with a thiopyrylium cation was synthesized. H4–PEG-Glu not only can quickly and effectively image mitochondria in acute myeloid leukemia (AML) cells, and induce G0/G1 phase arrest by the intrinsic mitochondrial apoptosis pathway w/o irradiation, but also exhibit moderate cytotoxicity against AML cancer cells in a dose dependent-manner without laser irradiation. The THP-1 cells treated with H4–PEG-Glu upon NIR laser irradiation showed enhanced chemo- and photothermal therapy (CPTT) with 93.07% ± 6.43 apoptosis by Annexin V staining. Meanwhile, H4–PEG-Glu displayed high synergistic CPTT effects in vivo, as well as specific NIR-II tumor imaging in AML patient derived PDX mouse models for the first time. Our work lays down a solid foundation for designing small-molecule NIR-II mitochondria-selective theranostic probes.Small-molecule subcellular organelle-targeting theranostic probes are crucial for early disease diagnosis and treatment. |
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