A self-immolative near-infrared fluorescent probe for identification of cancer cells and facilitating its apoptosis.

Hydrogen sulfide (H2S) plays a significant role in the onset and progression of cancer. It has led to increased interest in its potential as a diagnostic tool owing to its overexpression in cancer. However, research into the anti-cancer activity of H2S, particularly its ability to promote apoptosis, is hindered by the lack of effective detection tools. To gain a comprehensive understanding of the targeted efficacy of H2S in promoting cancer cell apoptosis, we designed and synthesized a self-immolative near-infrared fluorescent diagnostic probe, named YH-NO2. The activation of this self-immolative reaction is dependent on the presence of nitroreductase (NTR) overexpressed in tumor cells. The design of YH-NO2 involves releasing fluorophores through the activated self-immolative reaction for detection, while simultaneously releasing H2S-loaded self-immolative spacers to promote cancer cell apoptosis. Consequently, YH-NO2 achieves a seamless integration of recognizing and promoting cancer cell apoptosis through its self-immolative structure. This dual function allows YH-NO2 to recognize NTR activity in cells under varying hypoxia levels and differentiate between normal cells and cancer cells using imaging technology. Notably, YH-NO2 exhibits remarkable stability in cellular environments, providing controlled and selective H2S release, thereby targeting the elimination of cancer cells through the promotion of apoptosis. Furthermore, in vivo experiments have demonstrated that YH-NO2 can accurately identify tumor tissue and effectively reduce its size by utilizing its apoptosis-promoting properties. These findings not only provide further evidence for the anti-cancer activity of H2S but also offer valuable tools for understanding the complex relationship between H2S and cancer.

Exploring the Role of Mitochondrial Hydrogen Sulfide in Maintaining Polarity and mtDNA Integrity with a Multichannel Fluorescent Probe.

Abnormal mitochondrial state has been implicated in the pathogenesis of various diseases including neurodegenerative disorders, myopathies, cardiovascular diseases, and cancers. Assessing mitochondrial functionality can be achieved by monitoring alterations in mitochondrial polarity and mitochondrial DNA (mtDNA) integrity, which serve as valuable biomarkers. Hydrogen sulfide (H2S), a gaseous signaling molecule, plays a regulatory role in mitochondrial respiratory chain activity, ATP synthesis, and calcium ion balance, thereby influencing cellular metabolism and signal transduction. Investigating the interplay between mitochondrial H2S, polarity, and mtDNA can enhance our understanding of the underlying regulatory mechanisms involved in H2S-mediated mitochondrial functions. To address this, we designed a mitochondria-targeted multichannel fluorescent probe, HNA, capable of cascaded detection of H2S and polarity, as well as parallel detection of mtDNA. The probe exhibited a significant turn-on response to H2S, emitting at approximately 604 nm, while the product HNAP demonstrated high sensitivity to polarity within the wavelength range of 526-591 nm. Additionally, the probe was able to bind to DNA, resulting in an enhanced long-wave emission at 668 nm. Facilitated by HNA, our study provides novel insights into the role of mitochondrial H2S in maintaining mitochondrial polarity and validates its protective effect on mtDNA through antioxidative mechanisms. Overall, this work proposes a potential therapeutic strategy for modulating the inflammatory process in mitochondrial-related diseases.

ATP-triggered highly sensitive probes for super-resolution mitochondrial imaging and low-dose bioimaging.

Adenosine triphosphate (ATP), mainly produced in mitochondria, plays an important role in various pathological processes such as inflammation and acute liver injury. Fluorescence imaging is a powerful tool for imaging tissue structure and function in vivo. To date, the lack of biocompatible ATP probes with bright fluorescence emission has hindered their application in basic research and clinical trials. Here, we report a method for preparing ATP probes using a ZIF-90 potting dye, which produces bright ATP probes by encapsulating a modified high fluorescence quantum yield dye into a ZIF-90 skeleton. The nanoprobe does not fluoresce due to the coating. ATP can cooperate with Zn2+ to decompose the nanoprobe structure, release the dye and restore the fluorescence. Both nanoprobes ORhBSO2@ZIF-90 and SiRhBSO2@ZIF-90 showed higher sensitivity than the reported ATP nanoprobes with detection limits of 7.56 µM and 6.6 µM, and with lower doses (10 µg mL-1) of probes for cell imaging. In addition, SiRhBSO2@ZIF-90 has also been successfully used in the liver injury model. The ZIF-90 encapsulation strategy can retain the high fluorescence quantum yield and improve the biocompatibility of the dye.

Improving the fluorescence brightness of distyryl Bodipys by inhibiting the twisted intramolecular charge transfer excited state.

A new class of NIR distyryl Bodipy fluorescent dyes were developed with sulfone- and quaternary ammonium-modified piperidines as auxochromes instead of conventional dialkylamino auxochromes. Such modification markedly improved the fluorescence quantum yields due to the efficient inhibition of the twisted intramolecular charge transfer (TICT) state. Based on the dye platform, we developed a new fluorescent H2O2 probe via self-immolative chemistry, and confirmed its capability to sensitively and selectively sense H2O2in vitro and in vivo.

Design, synthesis, and bioimaging applications of a new class of carborhodamines.

We herein developed a new class of carborhodamines (CRs), i.e. 10-methoxy-substituted carborhodamines MCRs, by a simple synthesis procedure, which have absorption and emission wavelengths longer than classical CRs while retaining their excellent photophysical properties. Based on the MCR platform, we constructed the mitochondria-targeted fluorescent probe MCR-DMA and demonstrated its potential for sensing singlet oxygen (1O2) in living cells during the photodynamic therapy process.

Improving the quantum yields of fluorophores by inhibiting twisted intramolecular charge transfer using electron-withdrawing group-functionalized piperidine auxochromes.

Herein, we present that the negative inductive effect exerted by electron-withdrawing groups, such as sulfone groups, can obviously improve the ionization potential of amino auxochromes, thereby effectively inhibiting twisted intramolecular charge transfer (TICT) and markedly improving the quantum yields of several families of fluorophores in aqueous solution.