Journal
CHEMICAL SCIENCE
Volume 12, Issue 5, Pages 1843-1850Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d0sc04727a
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Funding
- National Key R&D Program of China [2020YFA0908800]
- NSFC [81773674, 81770179]
- Shenzhen Science and Technology Research Grant [JCYJ20190808152019182]
- Hubei Province Scientific and Technical Innovation Key Project [2020BAB058]
- Applied Basic Research Program of Wuhan Municipal Bureau of Science and Technology [2019020701011429]
- Local Development Funds of Science and Technology Department of Tibet [XZ202001YD0028C]
- Health Commission of Hubei Province Scientific Research Project [WJ2019M177, WJ2019M178, WJ2019H008]
- Fundamental Research Funds for the Central Universities [ZNJC201931]
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Novel NIR-II small-molecule probe H4-PEG-Glu showed effective imaging and treatment targeting mitochondria in acute myeloid leukemia cells, inducing cell apoptosis and exhibiting moderate cytotoxicity without laser irradiation. Enhanced chemo- and photothermal therapy effects were observed with laser irradiation, presenting high synergistic effects in vivo and specific tumor imaging in AML patient-derived PDX mouse models.
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 similar to 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 G(0)/G(1) 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.
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