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.

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.

Esterase-Activated, pH-Responsive, and Genetically Targetable Nano-Prodrug for Cancer Cell Photo-Ablation.

Activatable prodrugs have drawn considerable attention for cancer cell ablation owing to their high specificity in drug delivery systems. However, phototheranostic prodrugs with dual organelle-targeting and synergistic effects are still rare due to low intelligence of their structures. Besides, the cell membrane, exocytosis, and diffusional hindrance by the extracellular matrix reduce drug uptake. Moreover, the up-regulation of heat shock protein and short singlet-oxygen lifetime in cancer cells hamper photo-ablation efficacy, especially in the mono-therapeutic model. To overcome those obstacles, we prepare an esterase-activated DM nano-prodrug, which is conjugated by diiodine-substituted fluorogenic malachite green derivative (MG-2I) and phototherapeutic agent DPP-OH via hydrolyzable ester linkage, having pH-responsiveness and genetically targetable activity for dual organelles-targeting to optimize photo-ablation efficacy. The DM nanoparticles (NPs) present improved pH-responsive photothermal/photodynamic property by the protonation of diethylaminophenyl units in acidic environment. More importantly, the MG-2I and DPP-OH moieties can be released from DM nano-prodrug through overexpressed esterase; then specifically target lysosomes and mitochondria in CT-26 Mito-FAP cells. Hence, near-infrared DM NPs can trigger parallel damage in dual-organelles with strong fluorescence and effective phototoxicity, thus inducing serious mitochondrial dysfunction and apoptotic death, showing excellent photo-ablation effect based on esterase-activated, pH-responsive, and genetically targetable activities.

Complex Interplay Between Metabolism and CD4+ T-Cell Activation, Differentiation, and Function: a Novel Perspective for Atherosclerosis Immunotherapy.

Atherosclerosis is a complex pathological process that results from the chronic inflammatory reaction of the blood vessel wall and involves various immune cells and cytokines. An imbalance in the proportion and function of the effector CD4+ T-cell (Teff) and regulatory T-cell (Treg) subsets is an important cause of the occurrence and development of atherosclerotic plaques. Teff cells depend on glycolytic metabolism and glutamine catabolic metabolism for energy, while Treg cells mainly rely on fatty acid oxidation (FAO), which is crucial for determining the fate of CD4+ T cells during differentiation and maintaining their respective immune functions. Here, we review recent research achievements in the field of immunometabolism related to CD4+ T cells, focusing on the cellular metabolic pathways and metabolic reprogramming involved in the activation, proliferation, and differentiation of CD4+ T cells. Subsequently, we discuss the important roles of mTOR and AMPK signaling in regulating CD4+ T-cell differentiation. Finally, we evaluated the links between CD4+ T-cell metabolism and atherosclerosis, highlighting the potential of targeted modulation of CD4+ T-cell metabolism in the prevention and treatment of atherosclerosis in the future.

Co-Intercalation of Dual Charge Carriers in Metal-Ion-Confining Layered Vanadium Oxide Nanobelts for Aqueous Zinc-Ion Batteries.

Vanadium-based oxides with high theoretical specific capacities and open crystal structures are promising cathodes for aqueous zinc-ion batteries (AZIBs). In this work, the confined synthesis can insert metal ions into the interlayer spacing of layered vanadium oxide nanobelts without changing the original morphology. Furthermore, we obtain a series of nanomaterials based on metal-confined nanobelts, and describe the effect of interlayer spacing on the electrochemical performance. The electrochemical properties of the obtained Al2.65 V6 O13 ⋅ 2.07H2 O as cathodes for AZIBs are remarkably improved with a high initial capacity of 571.7 mAh ⋅ g-1 at 1.0 A g-1 . Even at a high current density of 5.0 A g-1 , the initial capacity can still reach 205.7 mAh g-1 , with a high capacity retention of 89.2 % after 2000 cycles. This study demonstrates that nanobelts confined with metal ions can significantly improve energy storage applications, revealing new avenues for enhancing the electrochemical performance of AZIBs.

Hollow Mesoporous Manganese Oxides: Application in Cancer Diagnosis and Therapy.

The precision, minimal invasiveness, and integration of diagnosis and treatment are critical factors for tumor treatment at the present. Although nanomedicine has shown the potential in tumor precision treatment, nanocarriers with high efficiency, excellent targeting, controlled release, and good biocompatibility still need to be further explored. Hollow mesoporous manganese oxides nanomaterials (HM-MONs), as an efficient drug delivery carrier, have attracted substantial attention in applications of tumor diagnosis and therapy due to their unique properties, such as tumor microenvironment stimuli-responsiveness, prominent catalytic activity, excellent biodegradation, and outstanding magnetic resonance imaging ability. The HM-MONs can not only enhance the therapeutic efficiency but also realize multimodal diagnosis of tumors. Consequently, it is necessary to introduce applications based on HM-MONs in cancer diagnosis and therapy. In this review, the representative progress of HM-MONs in synthesis is discussed. Then, several promising applications in drug delivery, bio-imaging, and bio-detection are highlighted. Finally, the challenges and perspectives of the anticancer applications are summarized, which is expected to provide meaningful guidance on further research.

Unlocking the High Capacity Ammonium-Ion Storage in Defective Vanadium Dioxide.

Aqueous ammonium-ion storage has been considered a promising energy storage competitor to meet the requirements of safety, affordability, and sustainability. However, ammonium-ion storage is still in its infancy in the absence of reliable electrode materials. Here, defective VO2 (d-VO) is employed as an anode material for ammonium-ion batteries with a moderate transport pathway and high reversible capacity of ≈200 mAh g-1 . Notably, an anisotropic or anisotropic behavior of structural change of d-VO between c-axis and ab planes depends on the state of charge (SOC). Compared with potassium-ion storage, ammonium-ion storage delivers a higher diffusion coefficient and better electrochemical performance. A full cell is further fabricated by d-VO anode and MnO2 cathode, which delivers a high energy density of 96 Wh kg-1 (based on the mass of VO2 ), and a peak energy density of 3254 W kg-1 . In addition, capacity retention of 70% can be obtained after 10 000 cycles at a current density of 1 A g-1 . What's more, the resultant quasi-solid-state MnO2 //d-VO full cell based on hydrogel electrolyte also delivers high safety and decent electrochemical performance. This work will broaden the potential applications of the ammonium-ion battery for sustainable energy storage.

Enhanced lasing properties of BUBD-1 film with multifunctional buffer layers doped with silver nanoparticles.

The organic semiconductor lasers (OSLs) have been seen as a promising light source for future applications. Achieving organic semiconductors with low amplified spontaneous emission (ASE) threshold is a key progress toward the electrically pumped OSLs. In this paper, the ASE properties of CBP: 2wt% BUBD-1 blend films were optimized using buffer layers containing silver nanoparticles (Ag NPs) with different ratios. Both photoluminescence intensity and ASE properties of blend films were optimized when the buffer layer with 25 vol% Ag NPs was introduced. The lowest ASE threshold is 0.47 µJ/Pulse (6.71 µJ/cm2), which reduces 67.6%, and the highest gain factor is 20.14 cm-1, which enhances 47.8% compared with that without buffer layers. The enhancement of ASE properties of blend films was ascribed to the four functions of the Ag NPs doped buffer layers, including the low refractive index of PMMA and the triple localized surface plasmon resonance (LSPR) effects of Ag NPs in buffer layers. The results show that the buffer layer modified by metal nanoparticles has great application potential in improving the lasing performance of organic small molecules.

Emerging photothermal-derived multimodal synergistic therapy in combating bacterial infections.

Due to the emerging bacterial resistance and the protection of tenacious biofilms, it is hard for the single antibacterial modality to achieve satisfactory therapeutic effects nowadays. In recent years, photothermal therapy (PTT)-derived multimodal synergistic treatments have received wide attention and exhibited cooperatively enhanced bactericidal activity. PTT features spatiotemporally controllable generation of hyperthermia that could eradicate bacteria without inducing resistance. The synergy of it with other treatments, such as chemotherapy, photo-dynamic/catalytic therapy (PDT/PCT), immunotherapy, and sonodynamic therapy (SDT), could lower the introduced laser density in PTT and avoid undesired overheating injury of normal tissues. Simultaneously, by heat-induced improvement of the bacterial membrane permeability, PTT is conducive for accelerated intracellular permeation of chemotherapeutic drugs as well as reactive oxygen species (ROS) generated by photosensitizers/sonosensitizers, and could promote infiltration of immune cells. Thereby, it could solve the currently existing sterilization deficiencies of other combined therapeutic modes, for example, bacterial resistance for chemotherapy, low drug permeability for PDT/PCT/SDT, adverse immunoreactions for immunotherapy, etc. Admittedly, PTT-derived synergistic treatments are becoming essential in fighting bacterial infection, especially those caused by antibiotic-resistant strains. This review firstly presents the classical and newly reported photothermal agents (PTAs) in brief. Profoundly, through the introduction of delicately designed nanocomposite platforms, we systematically discuss the versatile photothermal-derived multimodal synergistic therapy with the purpose of sterilization application. At the end, challenges to PTT-derived combinational therapy are presented and promising synergistic bactericidal prospects are anticipated.

All-in-One Nanomedicine: Multifunctional Single-Component Nanoparticles for Cancer Theranostics.

The development of cancer diagnostic imaging and treatment is a major concern worldwide. By integrating imaging and therapy into one theranostic nanoplatform for simultaneously detecting tumors, evaluating the targeting ability and timely monitoring therapeutic responses provide more opportunities for precision medicine. Among various theranostic nanosystems, a series of single-component nanoparticles (NPs) have been developed for "all-in-one" theranostics, which presents the unique properties of facile preparation, simple composition, defined structure, high reproducibility, and excellent biocompatibility. Specifically, utilizing single-component NPs for both diagnostics and therapeutics can reduce the possible numerous untoward side effects and risks to the living body. In this review, the recent progress of multifunctional single-component NPs in the applications of cancer theranostics is systematically summarized. Notably, the structure design, categories of NPs, targeted strategies, biomedical applications, potential barriers, challenges, and prospects for the future clinical practice of this rapidly growing field are discussed.

NIR-II Organic Nanotheranostics for Precision Oncotherapy.

Precision oncotherapy can remove tumors without causing any apparent iatrogenic damage or irreversible side effects to normal tissues. Second near-infrared (NIR-II) nanotheranostics can simultaneously perform diagnostic and therapeutic modalities in a single nanoplatform, which exhibits prominent perspectives in tumor precision treatment. Among all NIR-II nanotheranostics, NIR-II organic nanotheranostics have shown an exceptional promise for translation in clinical tumor treatment than NIR-II inorganic nanotheranostics in virtue of their good biocompatibility, excellent reproducibility, desirable excretion, and high biosafety. In this review, recent progress of NIR-II organic nanotheranostics with the integration of tumor diagnosis and therapy is systematically summarized, focusing on the theranostic modes and performances. Furthermore, the current status quo, problems, and challenges are discussed, aiming to provide a certain guiding significance for the future development of NIR-II organic nanotheranostics for precision oncotherapy.

Type I Photosensitizers Revitalizing Photodynamic Oncotherapy.

Photodynamic therapy (PDT) has shown great potential for tumor treatment with merits of non-invasiveness, high selectivity, and minimal side effects. However, conventional type II PDT relying on 1 O2 presents poor therapeutic efficacy for hypoxic tumors due to the oxygen-dependent manner. Alternatively, emerging researches have demonstrated that type I PDT exhibits superiority over type II PDT in tumor treatment owing to its diminished oxygen-dependence. In this review, state-of-the-art studies concerning recent progress in type I photosensitizers are scrutinized, emphasizing the strategies to construct highly effective type I photosensitizers. As the foundation, basic principles of type I PDT are presented, and up-to-date type I photosensitizers are summarized and classified based on their attributes. Then, a literature review of representative type I photosensitizers (including nanomaterials and small molecules) is presented with impetus to delineate their novel designs, action mechanisms, as well as anticancer PDT applications. Finally, the remaining challenges and development directions of type I photosensitizers are outlined, highlighting key scientific issues toward clinical translations.

Thrombin Based Photothermal-Responsive Nanoplatform for Tumor-Specific Embolization Therapy.

The specific coagulation in the tumor vasculature has the potential for the ablation of solid tumors by cutting off the blood supply. However, the safe delivery of effective vessel occluding agents in the tumor-specific embolization therapy remains challenging. Herein, it is reported that the photothermal responsive tumor-specific embolization therapy based on thrombin (Thr) is delivered by intravenous injection via the phase-change materials (PCM)-based nanoparticles. The wax sealing profile of PCM enables safe delivery and prevents the preleakage of Thr in the blood circulation. While in the tumor site, the thermal effect induced by IR780 triggers the melting of PCM and rapidly releases Thr to generate coagulation in the tumor blood vessels. Based on the safe delivery and controllable release of Thr, thermal responsive tumor-specific embolization therapy could be achieved with high efficiency and no significant damage to normal organs and tissues. The safe administration of Thr to induce vascular infarction in tumors based on PCM nanoparticles in this work shows a promising strategy for improving the therapeutic specificity and efficacy of coagulation-based tumor therapy.