Photoacoustic/Fluorescence Dual-Modality Probe for Biothiol Discrimination and Tumor Diagnosis in Cells and Mice

Abstract

Developing probes to simultaneously detect and discriminate biothiols is important, yet challenging. Activatable photoacoustic (PA) probes for discriminating biothiols in vivo are still lacking, and this hinders the diagnosis of thiol-related diseases. Herein we present the first PA and fluorescence dual-modality probe MB-NBD for discriminating different biothiol species. The probe has the advantages of both fluorescence imaging and PA imaging (high sensitivity and deep penetration) with distinct signal patterns toward hydrogen sulfide (H2S), cysteine/homocysteine (Cys/Hcy), and glutathione (GSH) treatment. The biothiol-activated product of MB-NBD exhibits enhancements in near-infrared fluorescence (NIRF) at 690 nm and absorbance/PA at 664 nm upon fast reaction, allowing it to selectively detect biothiol species over other reactive species. On the other hand, MB-NBD displays characteristic absorbance enhancement at 547 nm toward H2S, rendering specific detection of H2S. In addition, the specific enhancements in absorbance/PA at 470 nm and fluorescence at 550 nm toward Cys/Hcy treatment endows the probe with the capability of selectively detecting Cys/Hcy. Furthermore, MB-NBD is able to discriminate Cys and GSH by fluorescent imaging in live-cell and ratiometric PA imaging in mice experiments. MB-NBD has been successfully used to diagnose tumors by dual-channel ratiometric PA imaging.

Nanozyme Sensor Array Based on Porphyrin-Modified CoMoO4 to Detect and Distinguish Biologically Important Thiols

“…In addition, GSH plays an important role in maintaining the physiological functions of cells including intracellular redox reaction, foreign body metabolism, signal transduction, and gene regulation . As studied, the fluorescent probe has been considered as the accurate method for the detection of biothiol , due to its high selectivity and sensitivity. However, this fluorescent probe method caused some inevitable disadvantages, such as high requirements for instruments and equipment, inconvenient pretreating of samples, and so on.…”

Adaptive dual-speed ultrasound and photoacoustic computed tomography

“…Using one set of the ultrasonic transducer and data acquisition system, PACT and ultrasonography can be seamlessly combined for co-registered images with complementary contrasts [9] , [10] . Dual-modal US/PA imaging has demonstrated attractive prospects in early cancer diagnosis [11] , [12] , [13] , [14] , imaging-guided biopsy, and surgical navigation [15] , [16] , [17] . Especially, full-ring dual-modal US/PA imaging offers full view angle and fewer streak artifacts and has been widely used in various preclinical and clinical imaging [18] , [19] .…”

Rational design of a dual-reactive probe for imaging the biogenesis of both H2S and GSH froml-Cys rather thand-Cys in live cells

“…8 In addition, probes with multiple reaction sites have been rationally designed for distinguishing different biothiols from each other with different emission channels. 9 It is noted that a strategy of using multi-reactive multi-quenching probes has been demonstrated to be useful for highly sensitive and selective detection of biothiols and other analytes. 10,11 Attachment of multi-reactive quenchers to the same fluorophore results in low-background fluorescence of the probe due to the multi-quenching fashions through multiplication effects, 11 which can be used to enhance the sensitivity and selectivity of the detection in complex biological environments.…”