Au-Se bonded nanoprobe for prostate specific antigen detection in serum.

The detection of prostate specific antigen (PSA) in serum can realize early diagnosis of prostate cancer and prevent the occurrence of prostate tumors, as well as offering guidance during the therapy. Herein, a Au-Se bonded nanoprobes that can specifically detect PSA was designed and constructed. The peptide chains that can be specifically cleaved by PSA were firstly functionalized with fluorescent dye and selenol, and then bind to the Au nanoparticles to produce the probe. The dye's fluorescence was quenched due to the FRET effect, but recovered by PSA's cutting. The nanoprobe can detect PSA in serum with extraordinary anti-interference ability against other proteins (detection range 1-40 ng/mL). This work provides a new method for the detection of PSA in serum, and has potential guiding significance for clinical PSA detection.

Se-modified gold nanorods for enhancing the efficiency of photothermal therapy: avoiding the off-target problem induced by biothiols.

Tumor-targeting gold nanorods (AuNRs) assembled through Au-S bonds have been widely used for photothermal therapy (PTT) via intravenous injection. However, with extended in vivo circulation times, biothiols can replace some S-modified targeting ligands on the surface of the AuNRs, which lowers their targeting efficacy towards cancer cells, resulting in a non-ideal PTT effect. To address this problem, herein, we utilized Se-modified AuNRs to establish a dual functional nanoprobe (Casp-RGD-Se-AuNRs) for improving the therapeutic effect and real-time monitoring of Caspase-9 levels to indicate the degree of cell apoptosis. The experiments demonstrated that the Casp-RGD-Se-AuNRs are better at avoiding interference from biothiols than the S-modified nanoprobe (Casp-RGD-S-AuNRs) for extended blood-circulation times after intravenous injection, significantly improving the PTT efficacy via more effectively targeting cancer cells. Simultaneously, the change of Caspase-9 levels visually shows the degree of apoptosis. Moreover, an in vivo study showed that, compared with the S-modified nanoprobe, the Se-modified nanoprobe exhibits a higher delivery efficiency to the tumor region after intravenous injection (accumulation in the tumor increased by 87%) and a better anticancer efficacy under NIR light irradiation (the tumor inhibition rate increased 6-fold). This work provides a valuable strategy to overcome the off-target problem, and new ideas for avoiding interference by biomolecules during blood circulation.

Hydrogen selenide, a vital metabolite of sodium selenite, uncouples the sulfilimine bond and promotes the reversal of liver fibrosis.

Sodium selenite has alleviating effects on liver fibrosis; however, its therapeutic molecular mechanism remains unclear. Herein, hydrogen selenide, a major metabolite of Na2SeO3, was tested to uncouple the sulfilimine bond in collagen IV, the biomarker of liver fibrosis. A mouse model of liver fibrosis was constructed via a CCl4-induced method, followed by the administration of 0.2 mg kg-1 Na2SeO3 via gavage three times per week for 4 weeks. Changes in H2Se, NADPH, and H2O2 levels were monitored in real time by using NIR-H2Se, DCI-MQ-NADPH, and H2O2 probes in vivo, respectively. H2Se continuously accumulated in the liver throughout the Na2SeO3 treatment period, but the levels of NADPH and H2O2 decreased. The expression of collagen IV was analyzed through Western blot and liquid chromatography-mass spectrometry. Results confirmed that the sulfilimine bond of collagen IV in the fibrotic mouse livers could be broken by H2Se with the Na2SeO3 treatment. Therefore, the therapeutic effect of Na2SeO3 on liver fibrosis could be mainly attributed to H2Se that uncoupled the sulfilimine bond to induce collagen IV degradation. This study provided a reasonable explanation for the molecular mechanism of the in vivo function of Na2SeO3 and the prevention of liver fibrosis by administering inorganic selenium.

Tricolor imaging of MMPs to investigate the promoting roles of inflammation on invasion and migration of tumor cells.

The expression levels of matrix metalloproteinases (MMPs) are closely related to the degree of inflammation which facilitates tumor cells' invasion and migration. A tricolor fluorescence nanoprobe based on high-fidelity gold-selenium (Au-Se) nanoplatform was designed and constructed for simultaneously imaging matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-7 (MMP-7) and matrix metalloproteinase-9 (MMP-9) to thoroughly investigate the tumor cells' invasion and migration behaviors under inflammation environment. The nanoprobe was assembled by attaching Au NPs with three different peptide substrates respectively labeled with fluorescein isothiocyanate (FITC), 5-carboxytetramethylrhodamine (5-TAMRA) and cyanine 5 (Cy5) via the Au-Se bond. The nanoprobe can specifically respond to MMP-2/7/9, thereby triggering the fluorophores' fluorescence that quenched previously by fluorescence resonance energy transfer (FRET) to realize the MMP-2/7/9's visualization in biological systems. Moreover, as the inflammation stimulated by different concentrations lipopolysaccharide (LPS), the expression of MMP-2/7/9 in SMMC-7721 cells was observed to be significantly enhanced by confocal laser scanning microscope (CLSM) imaging, and inflammation was further proved to intensify SMMC-7721 cells' invasion and migration by transwell invasion and migration experiments. Therefore, the nanoprobe can be used to monitor biomarkers to provide a visual system for the degree of invasion and migration of tumor cells in an inflammatory environment, and also offer a new strategy for the study of the correlation between various active biomacromolecules and specific intracellular pathways in cells.