Ultrabright Green-Emissive Nanodots for Precise Biological Visualization.

Developing general methods to fabricate water-dispersible and biocompatible fluorescent probes will promote different biological visualization applications. Herein, we report a metal-facilitated method to fabricate ultrabright green-emissive nanodots via the one-step solvothermal treatment of rose bengal, ethanol, and various metal ions. These metal-doped nanodots show good water dispersity, ultrahigh photoluminescence quantum yields (PLQYs) (e.g., the PLQY of Fe-doped nanodots (FeNDs) was ∼97%), and low phototoxicity. Owing to the coordination effect of metal ions, the FeNDs realize glutathione detection with outstanding properties. Benefiting from the high endoplasmic reticulum (ER) affinity of the chloride group, the FeNDs can act as an ER tracker with long ER imaging capacity (FeNDs: >24 h; commercial ER tracker: ∼1 h) and superb photostability and can achieve tissue visualization in living Caenorhabditis elegans. The metal-doped nanodots represent a general nanodot preparation method and may shed new light on diverse biological visualization uses.

Aromaticity Tuning of Heavy-Atom-Free Photosensitizers for Singlet Fission-Enhanced Immunogenic Photodynamic Oncotherapy.

The quantum yield of reactive oxygen species is of central importance for the development of organic photosensitizers and photodynamic therapy (PDT). A common molecular design approach for optimizing organic photosensitizers involves the incorporation of heavy atoms into their backbones. However, this raises concerns regarding heightened dark cytotoxicity and a shortened triplet-state lifetime. Herein, we demonstrate a heavy-atom-free (HAF) photosensitizer design strategy founded on the singlet fission (SF) mechanism for cancer PDT. Through the "single-atom surgery" approach to deleting oxygen atoms in pyrazino[2,3-g]quinoxaline skeleton photosensitizers, photosensitizers PhPQ and TriPhPQ are produced with Huckel's aromaticity and Baird's aromaticity in the ground state and triplet state, respectively, enabling the generation of two triplet excitons through SF. The SF process endows photosensitizer PhPQ with an ultrahigh triplet-state quantum yield (186%) and an outstanding 1O2 quantum yield (177%). Notably, HAF photosensitizers PhPQ and TriPhPQ enhanced PDT efficacy and potentiated αPD-L1 immune check blockade therapy in vivo, which show their promise for translational oncology treatment.

MXene-Fiber Composite Membranes for Permeable and Biocompatible Skin-Interfaced Iontronic Mechanosensing.

Artificial ionic sensory systems, bridging the divide between biological systems and electronics, mimic human skin functions but face critical challenges with biocompatibility, comfort, signal stability, and simplifying packaging. Here, we present a simple and permeable skin-interfaced iontronic mechanosensing (SIIM) architecture that integrates human skin as natural ionic material and hierarchically porous MXene-fiber composite membranes as sensing electrodes. The SIIM system eliminates complex ionic material design and multilayer matrix, exhibiting ultrahigh pressure sensitivities (5.4 kPa-1, <75 Pa), a low detection limit (6 Pa), excellent output stability along with high permeability to minimize the impact of sweating on sensing. The noncytotoxic nature of SIIM electrodes ensures excellent biocompatibility (>97% cell coincubational viability), facilitating long-term wearability and high biosafety. Furthermore, the scalable SIIM configuration integrated with matrix smart gloves, effectively monitors human physical movements. This SIIM-based sensor with marked sensing capabilities, structural simplicity, and scalability, holds promising potential in diverse wearable applications.

Enzyme-Like Photocatalytic Octahedral Rh/Ag2MoO4 Accelerates Diabetic Wound Healing by Photo-Eradication of Pathogen and Relieving Wound Hypoxia.

The harsh environment of diabetic wounds, including bacterial infection and wound hypoxia, is not conducive to wound healing. Herein, an enzyme-like photocatalytic octahedral Rh/Ag2MoO4 is developed to manage diabetic-infected wounds. The introduction of Rh nanoparticles with catalase-like catalytic activity can enhance the photothermal conversion and photocatalytic performance of Rh/Ag2MoO4 by improving near-infrared absorbance and promoting the separation of electron-hole pairs, respectively. Rh/Ag2MoO4 can effectively eliminate pathogens through a combination of photothermal and photocatalytic antibacterial therapy. After bacteria inactivation, Rh/Ag2MoO4 can catalyze hydrogen peroxide to produce oxygen to alleviate the hypoxic environment of diabetic wounds. The in vivo treatment effect demonstrated the excellent therapeutic performance of Rh/Ag2MoO4 on diabetic infected wounds by removing infectious pathogens and relieving oxygen deficiency, confirming the potential application of Rh/Ag2MoO4 in the treatment of diabetic infected wounds.

3D Printed MXene-Based Wire Strain Sensors with Enhanced Sensitivity and Anisotropy.

Stretchable strain sensors play a crucial role in intelligent wearable systems, serving as the interface between humans and environment by translating mechanical strains into electrical signals. Traditional fiber strain sensors with intrinsic uniform axial strain distribution face challenges in achieving high sensitivity and anisotropy. Moreover, existing micro/nano-structure designs often compromise stretchability and durability. To address these challenges, a novel approach of using 3D printing to fabricate MXene-based flexible sensors with tunable micro and macrostructures.  Poly(tetrafluoroethylene) (PTFE) as a pore-inducing agent is added into 3D printable inks to achieve controllable microstructural modifications. In addition to microstructure tuning, 3D printing is employed for macrostructural design modifications, guided by finite element modeling (FEM) simulations. As a result, the 3D printed sensors exhibit heightened sensitivity and anisotropy, making them suitable for tracking static and dynamic displacement changes. The proposed approach presents an efficient and economically viable solution for standardized large-scale production of advanced wire strain sensors.

Tumor Microenvironment-Induced Drug Depository for Persistent Antitumor Chemotherapy and Immune Activation.

Herein, a drug-loading nanosystem that can in situ form drug depository for persistent antitumor chemotherapy and immune regulation is designed and built. The system (DOX@MIL-LOX@AL) is fabricated by packaging alginate on the surface of Doxorubicin (DOX) and lactate oxidase (LOX) loaded MIL-101(Fe)-NH2 nanoparticle, which can easily aggregate in the tumor microenvironment through the cross-linking with intratumoral Ca2+. Benefiting from the tumor retention ability, the fast-formed drug depository will continuously release DOX and Fe ions through the ATP-triggered slow degradation, thus realizing persistent antitumor chemotherapy and immune regulation. Meanwhile, LOX in the non-aggregated nanoparticles is able to convert the lactic acid to H2O2, which will be subsequently decomposed into ·OH by Fe ions to further enhance the DOX-induced immunogenic death effect of tumor cells. Together, with the effective consumption of immunosuppressive lactic acid, long-term chemotherapy, and oxidation therapy, DOX@MIL-LOX@AL can execute high-performance antitumor chemotherapy and immune activation with only one subcutaneous administration.

The insightful water quality analysis and predictive model establishment via machine learning in dual-source drinking water distribution system.

Dual-source drinking water distribution systems (DWDS) over single-source water supply systems are becoming more practical in providing water for megacities. However, the more complex water supply problems are also generated, especially at the hydraulic junction. Herein, we have sampled for a one-year and analyzed the water quality at the hydraulic junction of a dual-source DWDS. The results show that visible changes in drinking water quality, including turbidity, pH, UV254, DOC, residual chlorine, and trihalomethanes (TMHs), are observed at the sample point between 10 and 12 km to one drinking water plant. The average concentration of residual chlorine decreases from 0.74 ± 0.05 mg/L to 0.31 ± 0.11 mg/L during the water supplied from 0 to 10 km and then increases to 0.75 ± 0.05 mg/L at the end of 22 km. Whereas the THMs shows an opposite trend, the concentration reaches to a peak level at hydraulic junction area (10-12 km). According to parallel factor (PARAFAC) and high-performance size-exclusion chromatography (HPSEC) analysis, organic matters vary significantly during water distribution, and tryptophan-like substances and amino acids are closely related to the level of THMs. The hydraulic junction area is confirmed to be located at 10-12 km based on the water quality variation. Furthermore, data-driven models are established by machine learning (ML) with test R2 higher than 0.8 for THMs prediction. And the SHAP analysis explains the model results and identifies the positive (water temperature and water supply distance) and negative (residual chlorine and pH) key factors influencing the THMs formation. This study conducts a deep understanding of water quality at the hydraulic junction areas and establishes predictive models for THMs formation in dual-sources DWDS.

Acidity-Responsive Nanoreactors Destructed "Warburg Effect" for Toxic-Acidosis and Starvation Synergistic Therapy.

"Warburg Effect" shows that most tumor cells rely on aerobic glycolysis for energy supply, leading to malignant energy deprivation and an "internal alkaline external acid" tumor microenvironment. Destructing the "Warburg Effect" is an effective approach to inhibit tumor progression. Herein, an acidity-responsive nanoreactor (Au@CaP-Flu@HA) is fabricated for toxic acidosis and starvation synergistic therapy. In the nanoreactor, the fluvastatin (Flu) could reduce lactate efflux by inhibiting the lactate-proton transporter (monocarboxylate transporters, MCT4), resulting in intracellular lactate accumulation. Meanwhile, the glucose oxidase-mimic Au-nanocomposite consumes glucose to induce cell starvation accompanied by gluconic acid production, coupling with lactate to exacerbate toxic acidosis. Also, the up-regulated autophagic energy supply of tumor cells under energy deprivation and hypoxia aggravation is blocked by autophagy inhibitor CaP. Cellular dysfunction under pHi acidification and impaired Adenosine Triphosphate (ATP) synthesis under starvation synergistically promote tumor cell apoptosis. Both in vitro and in vivo studies demonstrate that this combinational approach of toxic-acidosis/starvation therapy could effectively destruct the "Warburg Effect" to inhibit tumor growth and anti-metastatic effects.

PtMo-Au Metalloenzymes Regulated Tumor Microenvironment for Enhanced Sonodynamic/Chemodynamic/Starvation Synergistic Therapy.

The clinical application of sonodynamic therapy (SDT) is greatly limited by the low quantum yield of sonosensitizers and tumor microenvironment (TME). Herein, PtMo-Au metalloenzyme sonosensitizer is synthesized by modulating energy band structure of PtMo with Au nanoparticles. The surface deposition of Au simultaneously solves the carrier recombination and facilitates the separation of electrons (e- ) and holes (h+ ), effectively improving the reactive oxygen species (ROS) quantum yield under ultrasound (US). The catalase-like activity of PtMo-Au metalloenzymes alleviates hypoxia TME, thus enhancing the SDT-induced ROS generation. More importantly, tumor overexpressed glutathione (GSH) can serve as the hole scavenger, which is accompanied by a persistent depletion of the GSH, thus inactivating GPX4 for the accumulation of lipid peroxides. The distinctly facilitated SDT-induced ROS production is coupled with chemodynamic therapy (CDT)-induced hydroxyl radicals (•OH) to exacerbate ferroptosis. Furthermore, Au with glucose oxidase mimic activity can not only inhibit intracellular adenosine triphosphate (ATP) production and induce tumor cell starvation but also generate H2 O2 to facilitate CDT. In general, this PtMo-Au metalloenzyme sonosensitizer optimizes the defects of conventional sonosensitizers through surface deposition of Au to regulate TME, providing a novel perspective for US-based tumor multimodal therapy.

Recent Nanotechnologies to Overcome the Bacterial Biofilm Matrix Barriers.

Bacterial biofilm-related infectious diseases severely influence human health. Under typical situations, pathogens can colonize inert or biological surfaces and form biofilms. Biofilms are functional aggregates that coat bacteria with extracellular polymeric substances (EPS). The main reason for the failure of biofilm infection treatment is the low permeability and enrichment of therapeutic agents within the biofilm, which results from the particular features of biofilm matrix barriers such as negatively charged biofilm components and highly viscous compact EPS structures. Hence, developing novel therapeutic strategies with enhanced biofilm penetrability is crucial. Herein, the current progress of nanotechnology methods to improve therapeutic agents' penetrability against biofilm matrix, such as regulating material morphology and surface properties, utilizing the physical penetration of nano/micromotors or microneedle patches, and equipping nanoparticles with EPS degradation enzymes or signal molecules, is first summarized. Finally, the challenges, perspectives, and future implementations of engineered delivery systems to manage biofilm infections are presented in detail.