Simultaneous Detection of Aldehyde Metabolites by Light-Assisted Ambient Ionization Mass Spectrometry.

In the clinic, small-molecule metabolites (SMMs) in blood are highly convincing indicators for disease diagnosis, such as cancer. However, challenges still exist for detection of SMMs due to their low concentration and complicated components in blood. In this work, we report the design of a novel "selenium signature" nanoprobe (Se nanoprobe) for efficient identification of multiple aldehyde metabolites in blood. This Se nanoprobe consists of magnetic nanoparticles that can enrich aldehyde metabolites from a complex environment, functionalized with photosensitive "selenium signature" hydrazide molecules that can react with aldehyde metabolites. Upon irradiation with UV, the aldehyde derivatives can be released from the Se nanoprobe and further sprayed by mass spectrometry through ambient ionization (AIMS). By quantifying the selenium isotope distribution (MS/MS) from the derivatization product, accurate detection of several aldehyde metabolites, including valeraldehyde (Val), heptaldehyde (Hep), 2-furaldehyde (2-Fur), 10-undecenal aldehyde (10-Und), and benzaldehyde (Ben), is realized. This strategy reveals a new solution for quick and accurate cancer diagnosis in the clinic.

Identification of sulfhydryl-containing proteins and further evaluation of the selenium-tagged redox homeostasis-regulating proteins.

Chemoproteomic profiling of sulfhydryl-containing proteins has consistently been an attractive research hotspot. However, there remains a dearth of probes that are specifically designed for sulfhydryl-containing proteins, possessing sufficient reactivity, specificity, distinctive isotopic signature, as well as efficient labeling and evaluation capabilities for proteins implicated in the regulation of redox homeostasis. Here, the specific selenium-containing probes (Se-probes) in this work displayed high specificity and reactivity toward cysteine thiols on small molecules, peptides and purified proteins and showed very good competitive effect of proteins labeling in gel-ABPP. We identified more than 6000 candidate proteins. In TOP-ABPP, we investigated the peptide labeled by Se-probes, which revealed a distinct isotopic envelope pattern of selenium in both the primary and secondary mass spectra. This unique pattern can provide compelling evidence for identifying redox regulatory proteins and other target peptides. Furthermore, our examiation of post-translational modification (PTMs) of the cysteine site residues showed that oxidation PTMs was predominantly observed. We anticipate that Se-probes will enable broader and deeper proteome-wide profiling of sulfhydryl-containing proteins, provide an ideal tool for focusing on proteins that regulate redox homeostasis and advance the development of innovative selenium-based pharmaceuticals.

Fabrication of a "Selenium Signature" Chemical Probe-Modified Paper Substrate for Simultaneous and Efficient Determination of Biothiols by Paper Spray Mass Spectrometry.

Significant efforts have been made to develop robust and reliable methods for simultaneous biothiols determination in different matrices, but there still exist the problems such as easy oxidation, tedious derivatization, and difficulty in discrimination, which brings unsatisfactory results in their accuracy and fast quantification in biological samples. To overcome these problems, a simultaneous biothiols detection method combining a "selenium signature" chemical probe and paper spray mass spectrometry (PS-MS) was proposed. In the strategy, the modified-paper substrate is used to enhance the analytical performance. Chemical probe Ebselen-NH2 that has a specific response to biothiols was designed and covalently fixed on the surface of an oxidized paper substrate. By the identification of derivatized product with distinctive selenium isotope distribution and employment of the optimized PS-MS method, qualitative and quantitative analysis of five biothiols including glutathione (GSH), cysteine (Cys), cysteinylglycine (CysGly), N-acetylcysteine (Nac), and homocysteine (Hcy) were realized. Biothiols in plasma and cell lysates were measured with satisfactory results. The established method not only provides a novel protocol for simultaneous determination of biothiols, but also is helpful for understanding the biological and clinical roles played by these bioactive small molecules.

Dually functioned core-shell NaYF4:Er3+/Yb3+@NaYF4:Tm3+/Yb3+ nanoparticles as nano-calorifiers and nano-thermometers for advanced photothermal therapy.

To realize photothermal therapy (PTT) of cancer/tumor both the photothermal conversion and temperature detection are required. Usually, the temperature detection in PTT needs complicated instruments, and the therapy process is out of temperature control in the present investigations. In this work, we attempt to develop a novel material for achieving both the photothermal conversion and temperature sensing and control at the same time. To this end, a core-shell structure with NaYF4:Er3+/Yb3+ core for temperature detection and NaYF4:Tm3+/Yb3+ shell for photothermal conversion was designed and prepared. The crystal structure and morphology of the samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Furthermore, the temperature sensing properties for the NaYF4:Er3+/Yb3+ and core-shell NaYF4:Er3+/Yb3+@NaYF4:Tm3+/Yb3+ nanoparticles were studied. It was found that the temperature sensing performance of the core-shell nanoparticles did not become worse due to coating of NaYF4:Tm3+/Yb3+ shell. The photothermal conversion behaviors were examined in cyclohexane solution based on the temperature response, the NaYF4:Er3+/Yb3+@NaYF4:Tm3+/Yb3+ core-shell nanoparticles exhibited more effective photothermal conversion than that of NaYF4:Er3+/Yb3+ nanoparticles, and a net temperature increment of about 7 °C was achieved by using the core-shell nanoparticles.

Use of selenium to detect mercury in water and cells: an enhancement of the sensitivity and specificity of a seleno fluorescent probe.

Seleno fluorescent probe: An organoselenium fluorescent probe (FSe-1) for mercury was designed based on the irreversible deselenation mechanism. FSe-1 exhibits an ultrahigh selectivity and sensitivity for Hg(2+) detection only for reactive selenium atom sites, due the strong affinity between Se and Hg. Furthermore, the new probe has been successfully used for imaging mercury ions in RAW 264.7 cells (a mouse macrophage cell line; see figure).Inspired by the antitoxic function of selenium towards heavy-metal ions, we designed an organoselenium fluorescent probe (FSe-1) for mercury. The reaction of FSe-1 and Hg(2+) is an irreversible deselenation mechanism based on the selenophilic character of mercury. FSe-1 exhibits an ultrahigh selectivity and sensitivity for Hg(2+) detection only for reactive selenium atom sites due to the strong affinity between Se and Hg. The experimental results proved that FSe-1 was selective for Hg(2+) ions over other relevant metal ions and bioanalytes, and also showed an enhancement in sensitivity of up to 1.0 nM, which is lower than the current Environmental Protection Agency standard for drinking water. Furthermore, the new probe has been successfully applied to the imaging of mercury ions in RAW 264.7 cells (a mouse macrophage cell line) with high sensitivity and selectivity.