Intracellular H2O2 levels are tightly regulated and can be modulated by various stimuli. A variety of nanozymes have been revealed with the ability to catalyze substrates of oxidoreductases, mostly including peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT), and some of them display multienzyme-like properties, which make them highly attractive for biomedical applications. However, the specific manifestations of nanozyemes within cells remain challenging to predict and detect. In this study, we developed a real-time, dynamic, and highly sensitive live-cell biosensor by expressing HyPer7 probe in the cytosol and mitochondria to monitor the cytosolic and mitochondrial H2O2 dynamics in a leukemia cell line THP-1. The successful expression of the probes in the cytosol and mitochondria was confirmed using confocal fluorescence microscopy. When the THP-1 cells were exposed to exogenous H2O2, the fluorescence intensity at 525 nm upon excitation with 405 nm lasers (referred to as F405) decreased, while that upon excitation with 488 nm lasers (referred to as F488) increased. Using this biosensor, we examined the dynamics of cytosolic and mitochondrial H2O2 in response to Daunorubicin, Fe3O4 nanozyme with Polyetherimide (PEI)- or Dextran (Dex)-modification, and Prussian blue nanozyme with different diameters. Results indicated that the particle size of PBNPs and surface modification of Fe3O4 play critical roles in their intracellular effects on the aspect of H2O2 modulation. The live-cell biosensors thus provide a powerful tool for detecting the variations of cytosolic and mitochondrial H2O2 in response to nanozymes, thereby facilitating a better understanding of the biological effects of nanozymes and their potential biomedical applications.
Chemotherapy is often hindered by issues associated with deficient drug selectivity and ineluctable toxic effects. The emerging realm of mechanochemistry has demonstrated significant promise in precise drug activation by using ultrasound-induced mechanical forces to regulate the chemical properties of compounds at the molecular level. Recently, we proved that the successful introduction of nanostructures to mechanochemistry could improve drug loading capacity and enhance their mechanical responsiveness. To further expand the application of the ultrasound-response drug activation strategy in nanosystems, in this context, we illustrate the preparation of a mechano-nanoswitch for spatiotemporal control of drug activation.
Porphyrins, a class of cyclic compounds featuring a metal ion at the core of their macrocyclic structure, have long been recognized as indispensable cofactors in natural enzymatic processes. These porphyrin-based enzymes enable a wide variety of complex biochemical transformations under mild conditions with high yield, regioselectivity and stereoselectivity. As mimics of P450 enzymes, the integration of porphyrins into artificial enzymatic systems to catalyze unnatural organic reactions represents a rapidly advancing research area. Such reactions, those typically catalyzed by small molecule catalysts, are of significant interest in synthetic chemistry. This mini-review explores the role of porphyrins in both enzyme-catalyzed natural and unnatural organic reactions, with a focus on their use as cofactors in engineered metalloenzymes.
Phototheranostic, as an emerging non-invasive cancer diagnosis and treatment modality, combines optical imaging with phototherapy, showcasing advantages such as precision, high efficiency, and low toxicity. The core of phototheranostics lies in photosensitizers (PSs), where molecular design and excited state dynamics regulation are crucial for performance optimization. This review systematically summarizes recent advancements in phototheranostic agents, focusing on strategies for molecular design and their critical role in excited-state energy conversion. Through strategies such as molecular structure optimization, coordination modulation, and self-assembly, the excited-state energy dissipation pathways of phototheranostic agents are precisely regulated, achieving a functional output balance while significantly enhancing therapeutic efficacy. Novel phototheranostic agents integrate multifunctional designs to realize theranostic integration, offering innovative solutions for complex cancer treatment. Finally, this paper explores the development prospects of nanotechnology-based phototheranostic strategies, providing new perspectives and potential breakthroughs for the next generation of phototheranostics.
In early pregnancy, approximately 70% of women experience nausea and vomiting, with hyperemesis gravidarum (HG) can potentially lead to severe fluid and nutritional imbalances that require hospitalization. Although HG often resolves on its own in the early stages of pregnancy, its severity is linked to ketosis and elevated serum urea levels, as well as an increased risk of neurodevelopmental disorders in children. To further investigate the immune status of HG patients, we plan to conduct single-cell transcriptomic sequencing and plasma proteomic analysis of peripheral blood samples. This approach aims to elucidate the interactions and mechanisms of PBMCs and provide new insights into potential therapeutic interventions. Our findings indicate an increased proportion of neutrophils in HG patients, along with the upregulation of interferon genes and associated pathways. Notably, the activity of interferon-related TFs, such as STAT1, IRF7, and IRF9, was significantly elevated. Additionally, we observed a decrease in T cell activity in HG patients, while the functionality of NK cells and CD14+ monocytes was enhanced. The elevated plasma levels of NDEL1 may also have implications for fetal development. We have constructed a single-cell atlas of PBMCs from pregnant women with HG, which is expected to enhance our understanding of the immune response in HG and identify potential therapeutic targets for this condition.