Polyamine-Targeting Gefitinib Prodrug and its Near-Infrared Fluorescent Theranostic Derivative for Monitoring Drug Delivery and Lung Cancer Therapy

The therapy of non-small-cell lung cancer (NSCLC) is challenging because of poor prognosis. There are urgent demands for targeting anti-tumor drugs with reliable efficacy and clear pharmacokinetics

A highly selective turn-on near-infrared fluorescent probe for hydrogen sulfide detection and imaging in living cells

We have described a turn-on near-infrared fluorescent probe Cy-NO2 based on nitro group reduction for intracellular H2S detection. The probe employs cyanine dye as a fluorophore, and is equipped with a nitro group as a fluorescent modulator. It is readily employed for assessing intracellular H2S level changes, and confocal imaging is achieved successfully.We have described a turn-on near-infrared fluorescent probe Cy-NO2 based on nitro group reduction for intracellular H2S detection. The probe employs cyanine dye as a fluorophore, and is equipped with a nitro group as a fluorescent modulator. It is readily employed for assessing intracellular H2S level changes, and confocal imaging is achieved successfully

A reversible fluorescent probe based on C=N isomerization for the selective detection of formaldehyde in living cells and in vivo

Formaldehyde (FA) is an endogenously produced reactive carbonyl species (RCS) through biological metabolic processes whose concentration is closely related to human health and disease. Noninvasive and real-time detection of FA concentration in organisms is very important for revealing the physiological and pathological functions of FA. Herein, we design and synthesize a reversible fluorescent probe BOD-NH2 for the detection of FA in living cells and in vivo. The probe is composed of two moieties: the BODIPY fluorophore and the primary amino group response unit. The probe undergoes an intracellular aldimine condensation reaction with FA and forms imine (C=N) which will result in C=N isomerization and rotation to turn-off the fluorescence of the probe. It is important that the probe can show a reversible response to FA. The probe BOD-NH2 has been successfully applied for detecting and imaging FA in the cytoplasm of living cells. BOD-NH2 is capable of detecting fluctuations in the levels of endogenous and exogenous FA in different types of living cells. The probe can be used to visualize the FA concentration in fresh hippocampus and the probe can further qualitatively evaluate the FA concentrations in ex vivo-dissected organs. Moreover, BOD-NH2 can also be used for imaging in mice. The above applications make our new probe a potential chemical tool for the study of physiological and pathological functions of FA in cells and in vivo

Mitochondria-targeting near-infrared ratiometric fluorescent probe for selective imaging of cysteine in orthotopic lung cancer mice

Cysteine (Cys) plays significant roles in many physiological processes, although its normal concentration is maintained at the micromole level. Abnormally high levels of intracellular Cys can lead to many diseases including cancer. Recent years, many effective fluorescent probes have been developed for the selective detection of Cys against other biological thiols. Herein, we synthesized a ratiometric near-infrared (NIR) fluorescent probe Cy-OAcr for selective imaging of intracellular Cys. Cy-OAcr has a lipophilic iminium cation unit as the mitochondrial guider and an acrylate group as the Cys recognition unit as well as a fluorescence modulator for rearranging the conjugated Tc-electron system of cyanine fluorophore. Upon detection of Cys, there occurs a significant absorption and fluorescence spectral shift, which are desirably beneficial for ratiometric detection. This probe has high sensitivity and selectivity for Cys detection over glutathione (GSH), homocysteine (Hcy), and other biomolecules with a low limit of detection at 0.09 mu M. Probe Cy-OAcr is capable to detect and image Cys in three living cancer cell lines and their corresponding tumor-bearing mice models. More importantly, we successfully apply this fluorescent probe to evaluate the level of Cys in orthotopic lung cancer model. Imaging analyses reveal that the probe can discriminate tumor lesions from normal tissues, indicating its significant potential applications for clinical auxiliary diagnosis of cancer

Imaging of anti-inflammatory effects of HNO via a near-infrared fluorescent probe in cells and in rat gouty arthritis model

Nitroxyl (HNO) plays a crucial role in anti-inflammatory effects via the inhibition of inflammatory pathways, but the details of the endogenous generation of HNO still remain challenging owing to the complex biosynthetic pathways, in which the interaction between H2S and NO simultaneously generates HNO and polysulfides (H2Sn) in mitochondria. Moreover, nearly all the available fluorescent probes for HNO are utilized for imaging HNO in cells and tissues, instead of the in situ real-time detection of the simultaneous formation of HNO and H2Sn in mitochondria and animals. Here, we have developed a mitochondria-targeting near-infrared fluorescent probe, namely, Mito-JN, to detect the generation of HNO in cells and a rat model. The probe consists of three moieties: Aza-BODIPY as a fluorescent signal transducer, a triphenylphosphonium cation as a mitochondria-targeting agent, and a diphenylphosphinobenzoyl group as an HNO-responsive unit. The response mechanism is based on an aza-ylide intramolecular ester aminolysis reaction with fluorescence emissions on. Mito-JN displays high selectivity and sensitivity for HNO over various other biologically relevant species. Mito-JN was successfully used for the detection of the endogenous generation of HNO, which is derived from the crosstalk between H2S and NO in living cells. The additional generation of H2Sn was also confirmed using our previous probe Cy-Mito. The anti-inflammatory effect of HNO was examined in a cell model of LPS-induced inflammation and a rat model of gouty arthritis. The results imply that our probe is a good candidate for the assessment of the protective effects of HNO in inflammatory processes

Sequential Detection of Superoxide Anion and Hydrogen Polysulfides under Hypoxic Stress via a Spectral-Response-Separated Fluorescent Probe Functioned with a Nitrobenzene Derivative

Chronic hypoxic stress disrupts the intracellular redox homeostasis, leads to a series of physiological dysfunction, and finally results in many diseases including cancer and inflammatory and cardiovascular diseases. The intracellular redox status is related to the homeostasis between reactive oxygen species (ROS) and cellular antioxidant species. Superoxide anion (O-2(center dot-) is considered to be a precursor of ROS. As a member of reactive sulfur species, hydrogen polysulfides (H2Sn) are a class of antioxidants in cells, which act as an important regulator for the intracellular redox state. Therefore, trapping the cross-talk of O-2(center dot-) and H2Sn is a benefit for further understanding the physiological and pathological effects. Herein, we conceive a fluorescent probe HCy-ONO for sequential detection of O-2(center dot-) and H2Sn in cells and in mouse models. Based on a tandem reaction, the probe HCy-ONO can be used to detect O-2(center dot-) and H2Sn in different fluorescence collection windows without spectral overlap interference with limits of detection 90 and 100 nM, respectively. The strategy affords high sensitivity and selectivity for our detection in living cell models under continuous hypoxic and intermittent hypoxic conditions, revealing the reason for ischemia-reperfusion injury. Moreover, the probe can distinguish the inflamed tissue from normal tissue in acute peritonitis mouse model. Finally, our probe is successfully applied for imaging of O-2(center dot-) and H2Sn in the SH-SYSY tumor-bearing mouse model, which is helpful to elucidate the physiological and pathological processes. These data demonstrated that different hypoxic status lead to different concentrations between H2Sn and O-2(center dot-)