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Biothiols and its metabolite SO 2 derivatives play vital roles in various physiological processes. Although a few probes have been designed for monitoring the metabolism of biothiols, developing multi-signal fluorescent probes with practicability for simultaneously distinguishing biothiols (GSH, Cys and Hcy) and real-time visualizing SO 2 derivatives is an enormous challenge. To better visualize biothiols metabolism in vitro and vivo, we developed a novel multi-signal NIR fluorescent probe (probe 2) with mitochondria-targeted for distinguishing biothiols and its metabolism, based on an ICT-PET synergetic mechanism. Probe 2 with dual recognition sites distinguishing detected Cys/Hcy (Red-Green), GSH (Green) and SO 3 2- (Blue) via three channels. First probe 2 distinguished Cys and GSH to estimate main biothiols in living cells through the ratio changes of two well-defined emission bands (Red-Green), and then imaged its metabolite SO 2 with ratiometric fluorescence (Red-Blue), eliminating the interference by different biothiols. Notably, probe 2 exhibits satisfactory sensitivity (detection limit: 0.21, 0.13, 0.14 and 3.06 μM for Cys, Hcy, GSH and SO 3 2- , respectively), high selectivity, reliability at physiological pH, and rapid fluorescence response (within 10 min). Given these advantages, probe 2 has been successfully applied to the real-time monitor GSH metabolic process in MCF-7 cells and biothiols metabolism in breast cancer, suggesting biothiols metabolic changes might be a diagnostic indicator during cancer treatment. So probe 2 is a convenient and efficient tool for understanding the physiological functions of biothiols and its metabolism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

To explore how hypochlorous acid (HClO) affects human health, a highly sensitive, selective, and trace detection method for hypochlorite (ClO - ) is crucial for determining its non-negligible function in both environment and living systems. Herein, a dicyanoisophorone-phenylboronic acid-based novel ratiometric near-infrared fluorescent probe (Probe 1) was designed for the rapid and specific detection of ClO - based on the intramolecular charge transfer (ICT) mechanism. Excess addition of HClO to the Probe 1 solution, 186-times ratio (I 652 /I 582 ) augment were gained. And this probe provided a colorimetric and ratiometric fluorescence response to ClO - with a high selectivity, a rapid response (within 30 s), and had an extremely low detection limit (15.7 nM). In addition, owing to the good sensing properties and low cytotoxicity of Probe 1, it can be used to expediently visualize exogenous ClO - in HepG2 cells and endogenous ClO - in RAW264.7 macrophage cells. Furthermore, the probe was successfully used for the bioimaging of zebrafish with an acute inflammation. Thus, Probe 1 is a promising vehicle to identify the level of HClO in animals with associated diseases., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A novel redox-sensitive system for co-delivering hydrophobic drugs and hydrophilic siRNA or shRNA was developed by conjugating gambogic acid (GA) with poly(amido amine)s (PAAs) through amide bonds, which is called GA-conjugated PAAs (PAG). PAG can self-assemble into micelles as amphiphilic block copolymers, which exhibits an excellent loading ability for the co-delivery of docetaxel (DTX) and MMP-9 shRNA with adjustable dosing ratios. In addition, confocal microscopy, flow cytometry and in vitro transfection analyses demonstrated more efficient cellular internalization of DTX and MMP-9 shRNA after incubation with PAG/DTX- MMP-9 shRNA micelles (PAG/DTX-shRNA) than with free drugs. Unlike traditional amphiphilic copolymer micelles, GA conjugated in PAG possesses an intrinsic anticancer efficacy. The presence of disulfide bonds in PAAs enables rapid disassembly of PAG micelles in response to reducing agents, inducing the release of loaded drugs (DTX, GA and MMP-9 shRNA). In vitro cellular assays revealed that PAG/DTX-shRNA micelles inhibited MCF-7 cell proliferation more efficiently than the single drug or single drug-loaded micelles. In vivo biodistribution and anti-tumor effect studies using an MCF-7 breast cancer xenograft mouse model have indicated that PAG/DTX-shRNA micelles can enhance drug accumulation compared with the free drug, thereby sustaining the therapeutic effect on tumors. Additionally, PAG/DTX-shRNA micelles displayed a greater anti-tumor efficacy than Taxotere® and PAG-shRNA micelles. These results suggest that the redox-sensitive PAG platform is a promising co-delivery system for combining drugs and gene therapy for the treatment of cancer., Statement of Significance: The PAG micelles were designed by conjugating gambogic acid (GA) with poly(amido amine)s (PAAs), which would serve dual purposes as both gene and drugs co-delivery carrier and an anti-tumor prodrug. Unlike traditional amphiphilic micelles, GA conjugated in PAG could exert its intrinsic efficacy and provide synergistic antiproliferative effects with docetaxel (DTX) on MCF-7 cells. Disulfide bonds in PAG enables a rapid disassembly of PAG micelles in response to reducing agents and to release all loaded drugs (DTX, GA and MMP-9 shRNA) at tumor sites. PAG/DTX-shRNA micelles displayed greater anti-tumor efficacy than that of Taxotere®, indicating the design concept for PAG works well. And the strategy for PAG could be used to develop a series of similar co-delivery systems through conjugations of other small-molecule drugs with PAAs, such as doxorubicin, methotrexate and other drugs with carboxy groups in their structure., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)