Novel near-infrared frequency up-conversion luminescence probe for monitoring biothiols in vitro and in vivo

Biothiols including cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) play important roles in the antioxidant activity of cells, and a variety of diseases could be linked to their abnormal levels. Frequency up-conversion luminescence (FUCL) probes have low background fluorescence and cause low tissue damage; thus it is less harmful than Stokes shift luminescence probes, the traditional fluorescence probes. However, the utilization of FUCL probes for detection of biothiols has rarely been reported. In this work, we designed and synthesized a near-infrared (NIR) xanthene derivative IFU-1 and used as a frequency up-conversion luminescence probe to detect biothiols. The probe IFU-1 had high selectivity for biothiols and exhibited enhanced FUCL signals in response to them. In addition, it has extremely low limit of detection with regards to different biothiols: 4.8 nM for Cys; 6.2 nM for Hcy, and 9.5 nM for GSH, which are about 10 times lower than the detection limit of traditional excitation methods (63 nM for Cys, 31 nM for Hcy, and 76 nM for GSH). This work presents a novel approach for constructing FUCL biosensors.