Ultra-high signal-to-noise ratio near-infrared chemiluminescent probe for in vivo sensing singlet oxygen

Abstract

Singlet oxygen (¹O₂), as the primary reactive oxygen species in photodynamic therapy, can effectively induce excessive oxidative stress to ablate tumors and kill germs in clinical treatment. However, monitoring endogenous ¹O₂ is greatly challenging due to its extremely short lifetime and high reactivity in biological condition. Herein, we report an ultra-high signal-to-ratio near-infrared chemiluminescent probe (DCM-Cy) for the precise detection of endogenous ¹O₂ during photodynamic therapy (PDT). The methoxy moiety was removed from enolether unit in DCM-Cy to suppress the potential self-photooxidation reaction, thus greatly eliminating the photoinduced background signals during PDT. Additionally, the compact cyclobutane modification of DCM-Cy resulted in a significant 6-fold increase in cell permeability compared to conventional adamantane-dioxane probes. Therefore, our “step-by-step” strategy for DCM-Cy addressed the limitations of traditional chemiluminescent (CL) probes for ¹O₂, enabling effectively tracking of endogenous ¹O₂ level changes in living cells, pathogenic bacteria and mice in PDT.