All-in-one mitochondria-targeted NIR-II fluorophores for cancer therapy and imaging

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 probeH4-PEG-Gluwith a thiopyrylium cation was synthesized.H4-PEG-Glunot only can quickly and effectively image mitochondria in acute myeloid leukemia (AML) cells, and induce G0/G1phase 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 withH4-PEG-Gluupon NIR laser irradiation showed enhanced chemo- and photothermal therapy (CPTT) with 93.07% ± 6.43 apoptosis by Annexin V staining. Meanwhile,H4-PEG-Gludisplayed high synergistic CPTT effectsin 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.