Synergistic\nAnticancer\nEffects by Enhancing the G‑Quadruplex\nBinding of Nickel(II) Salphen Complexes through Coupling with S‑Doped\nCarbon Nanodots

In\nrecent decades, researchers have focused on developing\nless\ntoxic and more precise cancer therapies. Carbon nanodots (CDs) are\namong the most promising technologies due to their high biocompatibility,\ntunable fluorescence, and ability to facilitate photothermal and photodynamic\ntherapy. This study explores the synthesis and characterization of\ntwo CDs conjugated with Salphen metal complexes, namely, <b>CDs-PEG-M1</b> and <b>CDs-PEG-M2</b>, through Sonogashira coupling. Their\ninteraction with G-quadruplex DNA structures (G4s), motifs largely\ninvolved in cancer development, was evaluated using various spectroscopic\ntechniques. The results indicate that <b>CDs-PEG-M1</b> exhibits\ngreater effectiveness in stabilizing G4 structures compared to the\nmetal complex alone or nonfunctionalized CDs. This enhanced stabilization\nsuggests that <b>CDs-PEG-M1</b> could reduce the concentration\nof the metal complex needed for potential antitumor applications,\nthereby minimizing side effects on nontarget tissues. When tested\non breast cancer models (MDA-MB-231 as a triple-negative model and\nMCF-7 as a HER-2 positive model) and on a healthy cell line (HDFa),\nthe <b>CDs-PEG-M1</b> conjugate reduced cell viability in a\nconcentration- and time-dependent manner, showing greater potency\nand selectivity against cancer cells compared to virgin CDs and the\nfree <b>M1</b> complex. This synergistic anticancer effect,\ndriven by the interaction with G4 structures and reactive oxygen species\nproduction, underscores the potential of <b>CDs-PEG-M1</b> as\na targeted nanotheranostic tool.