Yinglong Wu

Single-atom nanozymes (SAEs) with a high catalytic performance have received worldwide attention in tumor therapy. The current SAEs still suffer from a low cell penetration efficiency and tumor accumulation, limiting their therapeutic effect during treatment. Herein, a typical urchin-like carbon-supported copper single-atom nanozyme (UCCSE) is designed for enhanced cascade chemodynamic therapy. The UCCSE is synthesized through a one-step carbonization-reduction strategy using dopamine and copper chloride as precursors. The structure endows UCCSE with enhanced membrane penetration via endocytosis and tumor cell uptake abilities. Upon internalization, the as-prepared UCCSE possesses peroxidase (POD)-mimicking activity for continuous hydroxyl radical (•OH) generation as well as glutathione peroxidase (GPx)-mimicking activity for glutathione depletion. Both cellular and animal experiments exhibit noteworthy needling-length-dependent tumor suppression effects with negligible systemic toxicity. This work provides a simple paradigm for enhanced tumor catalytic therapy through rational regulation of morphology.

Induction of systemic acquired resistance (SAR) in plants to control bacterial diseases has become an effective solution to the problems of agrochemical resistance and ecological environment damage caused by long-term and large-scale use of traditional bactericides. However, current SAR-inducing compounds are often unable to rapidly eliminate pathogenic bacteria in infected plant tissues to prevent further spread of the disease, severely restraining the potential for extensive application in agriculture. Herein, we address the limitations by developing a series of visible-light-absorbing aggregation-induced emission photosensitizers suitable for agricultural use. The photosensitizer (MTSQ2) is modulated by molecular engineering to have optimal optical properties, reactive oxygen species (ROS) generation efficiency, and bacterial targeting affinity, thereby exhibiting an effective antibacterial photodynamic activity against the phytopathogenic bacteria Pseudomonas syringae pv tomato DC3000 in the model plant Arabidopsis thaliana under white light illumination. Moreover, the ROS produced in situ by MTSQ2 can further regulate the ROS-AzA-G3P signaling pathway, thus allowing to induce SAR throughout the plant to prevent secondary infections. The current study can provide a feasible strategy for developing desirable photosensitizers to achieve sustainable management of plant diseases.

Despite targeted therapies like epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), non–small cell lung cancer (NSCLC) remains a clinical challenge due to drug resistance hampering their efficacy. Here, we designed an “AND” logic gate–based supramolecular therapeutic platform (HA-BPY-GEF-NPs) for the treatment of EGFR-TKI resistant NSCLC. This system integrates both internal and external stimuli–responsive mechanisms that need to be activated in a preset sequence, enabling it to precisely control drug release behavior for enhancing therapeutic precision. By programming the system to respond to sequential near-infrared (NIR) irradiation and enzyme (cathepsin B) inputs, the release of gefitinib is effectively confined to the tumor region. Moreover, the NIR irradiation induces reactive oxygen species production, suppressing tumor growth and inhibiting bypass signaling pathways. The designed drug delivery system offers a highly controlled and targeted therapeutic approach, effectively inhibiting tumor growth, suppressing bypass signaling pathways, and overcoming EGFR-TKI resistance, thus offering a potential solution for maximizing therapeutic benefits.

The development of chiral covalentorganic framework catalysts (CCOFs) to synthesize enantiopure organic compounds is crucial and highly desirable in synthetic chemistry. Photocatalytic asymmetric reactions based on CCOFs are eco-friendly and sustainable while they are still elaborate. In this work, we report a general bottom-up strategy to successfully synthesize several photoactive CCOFX (X = 1-5 and 1-Boc). The photoactive porphyrin building blocks are selected as knots and various secondary-amine-based chiral catalytic centers are immobilized on the pore walls of CCOFX through a rational design of benzoimidazole linkers. The porphyrin units act as light-harvesting antennae to generate photo-induced charge carriers for the activation of bromide during the photocatalytic asymmetric alkylation of aldehydes. Meanwhile, various aldehydes are activated by the chiral secondary amine to form the target products with a high yield (up to 97%) and ee value (up to 93%). The results significantly expand the scope to predesign CCOF photocatalysts for visible-light-driven asymmetric catalysis.

The development of efficient photocatalysts for N₂ fixation to produce NH₃ under ambient conditions remains a great challenge. Since covalent organic frameworks (COFs) possess predesignable chemical structures, good crystallinity, and high porosity, it is highly significant to explore their potential for photocatalytic nitrogen conversion. Herein, we report a series of isostructural porphyrin-based COFs loaded with Au single atoms (COFX-Au, X = 1-5) for photocatalytic N₂ fixation. The porphyrin building blocks act as the docking sites to immobilize Au single atoms as well as light-harvesting antennae. The microenvironment of the Au catalytic center is precisely tuned by controlling the functional groups at the proximal and distal positions of porphyrin units. As a result, COF1-Au decorated with strong electron-withdrawing groups exhibits a high activity toward NH₃ production with rates of 333.0 ± 22.4 μmol g^-1 h^-1 and 37.0 ± 2.5 mmol g_Au^-1 h^-1, which are 2.8- and 171-fold higher than that of COF4-Au decorated with electron-donating functional groups and a porphyrin-Au molecular catalyst, respectively. The NH₃ production rates could be further increased to 427.9 ± 18.7 μmol g^-1 h^-1 and 61.1 ± 2.7 mmol g_Au^-1 h^-1 under the catalysis of COF5-Au featuring two different kinds of strong electron-withdrawing groups. The structure-activity relationship analysis reveals that the introduction of electron-withdrawing groups facilitates the separation and transportation of photogenerated electrons within the entire framework. This work manifests that the structures and optoelectronic properties of COF-based photocatalysts can be finely tuned through a rational predesign at the molecular level, thus leading to superior NH₃ evolution.

Optoacoustic imaging is a hybrid biomedical imaging modality which collects ultrasound waves generated via photoexciting contrast agents in tissues and produces images of high resolution and penetration depth. As a functional optoacoustic imaging technique, multispectral optoacoustic imaging, which can discriminate optoacoustic signals from different contrast agents by illuminating samples with multi-wavelength lasers and then processing the collected data with specific algorithms, assists in the identification of a specific contrast agent in target tissues and enables simultaneous molecular and physiological imaging. Moreover, multispectral optoacoustic imaging can also generate three-dimensional images for biological tissues/samples with high resolution and thus holds great potential in biomedical applications. Contrast agents play essential roles in optoacoustic imaging, and they have been widely explored and applied as probes and sensors in recent years, leading to the emergence of a variety of new contrast agents. In this review, we aim to summarize the latest advances in emerging contrast agents, especially the activatable ones which can respond to specific biological stimuli, as well as their preclinical and clinical applications. We highlight their design strategies, discuss the challenges and prospects in multispectral optoacoustic imaging, and outline the possibility of applying it in clinical translation and public health services using synthetic contrast agents.

The presence of bacteria in the tumor can cause cancer resistance to chemotherapeutics. To fight against bacterium‐induced drug resistance, herein we design self‐traceable nanoreservoirs that are simultaneously loaded with gemcitabine (an anticancer drug) and ciprofloxacin (an antibiotic) and are decorated with hyaluronic acid for active tumor targeting. The nanoreservoirs have a pH‐sensitive gate and an enzyme‐responsive gate that can be opened in the acidic and hyaluronidase‐abundant tumor microenvironment to control drug release rates. Moreover, the nanoreservoirs can specifically target the tumor regions without eliciting evident toxicity to normal tissues, kill the intratumoral bacteria, and inhibit the tumor growth even in the presence of the bacteria. Unexpectedly, the nanoreservoirs can activate T cell‐mediated immune responses through promoting antigen‐presenting dendritic cell maturation and depleting immunosuppressive myeloid‐derived suppressor cells in bacterium‐infected tumors.

The presence of bacteria in the tumor can cause cancer resistance to chemotherapeutics. To fight against bacterium‐induced drug resistance, herein we design self‐traceable nanoreservoirs that are simultaneously loaded with gemcitabine (an anticancer drug) and ciprofloxacin (an antibiotic) and are decorated with hyaluronic acid for active tumor targeting. The nanoreservoirs have a pH‐sensitive gate and an enzyme‐responsive gate that can be opened in the acidic and hyaluronidase‐abundant tumor microenvironment to control drug release rates. Moreover, the nanoreservoirs can specifically target the tumor regions without eliciting evident toxicity to normal tissues, kill the intratumoral bacteria, and inhibit the tumor growth even in the presence of the bacteria. Unexpectedly, the nanoreservoirs can activate T cell‐mediated immune responses through promoting antigen‐presenting dendritic cell maturation and depleting immunosuppressive myeloid‐derived suppressor cells in bacterium‐infected tumors.