Abstract
The dysregulation of the c-Myc gene has been embroiled in the pathogenesis of various human cancers, including breast cancer. It is notable that ∼90% of c-Myc expression is regulated by c-Myc DNA sequence that forms G4. Fluorescent probes for imaging c-Myc DNA G4 may provide valuable insights into the biological functions of the c-Myc DNA G4 oncogene and offer promising opportunities for TNBC treatment. However, the existing probes for c-Myc DNA G4s still exhibit low specificity and short absorption/emission wavelengths. Herein, a novel anthocyanin derivative with NIR absorption/emission was engineered for the priority response to c-Myc DNA G4. A series of ligands for preferentially responding to c-Myc DNA G4s were developed by conjugating N-Cy with varied electron-donating groups. It is shown that the ligand CYMT using methylbenzothiazole as the electron-donating group displayed NIR absorption/emission, good selectivity, high fluorescence activation ratio and priority for the detection of c-Myc DNA G4s. Molecular docking experiments indicate that CYMT interacts with c-Myc DNA G4 through hydrogen bond and multiple π-π stacking. It was shown that CYMT could recognize DNA G4s and priority response to c-Myc DNA G4 in breast cancer. We further utilized CYMT to image the dynamics of DNA G4s under oxidative stress in live MDA-MB-231 cells. The ability of CYMT to monitor DNA G4s in vivo was showcased by time dependent detecting of DNA G4 levels in MDA-MB-231-transplanted mice breast tumor models. It was further confirmed the detection ability of CYMT for endogenous DNA G4 in vivo by collecting periocular blood from healthy nude mice and xenograft MDA-MB-231 mouse models. This probe may regard as a meaningful implement for investigating the physiological and pathological roles of c-Myc DNA G4s.