Heterojunction-Mediated Co-Adjustment of Band Structure and Valence State for Achieving Selective Regulation of Semiconductor Nanozymes.

Improving reaction selectivity is the next target for nanozymes to mimic natural enzymes. Currently, the majority of strategies in this field are exclusively applicable to metal-organic-based or organic-based nanozymes, while limited in regulating metal oxide-based semiconductor nanozymes. Herein, taking semiconductor Co3O4 as an example, a heterojunction strategy to precisely regulate nanozyme selectivity by simultaneously regulating three vital factors including band structure, metal valence state, and oxygen vacancy content is proposed. After introducing MnO2 to form Z-scheme heterojunctions with Co3O4 nanoparticles, the catalase (CAT)-like and peroxidase (POD)-like activities of Co3O4 can be precisely regulated since the introduction of MnO2 affects the position of the conduction bands, preserves Co in a higher oxidation state (Co3+), and increases oxygen vacancy content, enabling Co3O4-MnO2 exhibit improved CAT-like activity and reduced POD-like activity. This study proposes a strategy for improving reaction selectivity of Co3O4, which contributes to the development of metal oxide-based semiconductor nanozymes.

Polydopamine-encapsulated zinc peroxide nanoparticles to target the metabolism-redox circuit against tumor adaptability for mild photothermal therapy.

Regulating the metabolism-redox circuit of cancer cells has emerged as an attractive strategy to improve the therapeutic outcome, while often confronting the glaring issue of resistance due to the multiple adaptive responses of tumor cells. This study presents a simple yet efficient approach to regulate this circuit simultaneously against tumor adaptability by utilizing polydopamine-encapsulated zinc peroxide nanoparticles (ZnO2@PDA NPs). The nanoparticles could deliver large amounts of Zn2+ and H2O2 into tumor cells to unfold an intracellular self-amplifying loop for breaking the balance in zinc and redox homeostasis by H2O2-mediated endogenous Zn2+ release from metallothioneins due to its oxidation by H2O2 and Zn2+-induced in situ H2O2 production by disturbing mitochondrial respiration, ultimately disrupting tumor adaptability to exogenous stimuli. The elevated levels of Zn2+ and H2O2 also inhibited adenosine triphosphate (ATP) generation from glycolysis and mitochondrial respiration to disrupt energy adaptability. Furthermore, insufficient ATP supply could reduce glutathione and heat shock protein expression, thereby sensitizing oxidative stress and enabling PDA-mediated mild photothermal therapy (PTT). Consequently, this trinity nanoplatform, which integrated dual-starvation therapy, amplified oxidative stress, and mild PTT, demonstrated outstanding therapeutic effects and a facile strategy.

Nanozyme-Based Regulation of Cellular Metabolism and Their Applications.

Metabolism is the sum of the enzyme-dependent chemical reactions, which produces energy in catabolic process and synthesizes biomass in anabolic process, exhibiting high similarity in mammalian cell, microbial cell, and plant cell. Consequently, the loss or gain of metabolic enzyme activity greatly affects cellular metabolism. Nanozymes, as emerging enzyme mimics with diverse functions and adjustable catalytic activities, have shown attractive potential for metabolic regulation. Although the basic metabolic tasks are highly similar for the cells from different species, the concrete metabolic pathway varies with the intracellular structure of different species. Here, the basic metabolism in living organisms is described and the similarities and differences in the metabolic pathways among mammalian, microbial, and plant cells and the regulation mechanism are discussed. The recent progress on regulation of cellular metabolism mainly including nutrient uptake and utilization, energy production, and the accompanied redox reactions by different kinds of oxidoreductases and their applications in the field of disease therapy, antimicrobial therapy, and sustainable agriculture is systematically reviewed. Furthermore, the prospects and challenges of nanozymes in regulating cell metabolism are also discussed, which broaden their application scenarios.

Detection of 11 carbamate pesticide residues in raw and pasteurized camel milk samples using liquid chromatography tandem mass spectrometry: Method development, method validation, and health risk assessment.

This study aimed to use ultra-high-performance liquid chromatography coupled to a triple-quadrupole mass spectrometer to detect 11 carbamate pesticide residues in raw and pasteurized camel milk samples collected from the United Arab Emirates. A method was developed and validated by evaluating limits of detection, limits of quantitation, linearity, extraction recovery, repeatability, intermediate precision, and matrix effect. Due to the high protein and fat content in camel milk, a sample preparation step was necessary to avoid potential interference during analysis. For this purpose, 5 different liquid-liquid extraction techniques were evaluated to determine their efficiency in extracting carbamate pesticides from camel milk. The established method demonstrated high accuracy and precision. The matrix effect for all carbamate pesticides was observed to fall within the soft range, indicating its negligible effect. Remarkably, detection limits for all carbamates were as low as 0.01 µg/kg. Additionally, the coefficients of determination were >0.998, demonstrating excellent linearity. A total of 17 camel milk samples were analyzed, and only one sample was found to be free from any carbamate residues. The remaining 16 samples contained at least one carbamate residue, yet all detected concentrations were below the recommended maximum residue limits set by Codex Alimentarius and the European Union pesticide databases. Nonetheless, it is worth noting that the detected levels of ethiofencarb in 3 samples were close to the borderline of the maximum residue limit. To assess the health risk for consumers of camel milk, the hazard index values of carbofuran, carbaryl, and propoxur were calculated. The hazard index values for these 3 carbamate pesticides were all below 1, indicating that camel milk consumers are not at risk from these residues.

Hollow Cavity CaO2 @Polydopamine Nanocomposites for pH-Responsive Ca2+ -Enhanced Efficient Mild Hyperthermia in the NIR-II Region.

Second near-infrared (NIR-II) mild photothermal therapy with higher tissue penetration depth and less damage to healthy tissues is emerging as an attractive antitumor modality, but its therapeutic efficiency is dramatically suppressed by the resistance of heat shock proteins (HSPs). As a widely explored photothermal agent, the application of polydopamine (PDA) in the NIR-II region is hampered by low photothermal conversion efficiency (PCE). Herein, its PCE in the NIR-II region is improved by developing novel hollow cavity CaO2 @PDA nanocomposites through chelation-induced diffusion of inner core Ca2+ to the shell PDA to facilitate multiple reflections of laser in the cavity. Upon pH-responsive degradation of CaO2 , its structure is transformed into a stacked "nano-mesh" with excellent light absorption and an enlarged effective irradiation area. Overloading of Ca2+ ions not only induces downregulation of HSPs but also enhances interference of light on membrane potential, which further aggravate mitochondrial dysfunction and reduce the thermotolerance of tumor cells, promoting efficient mild hyperthermia of PDA in the NIR-II region.

Uncovering the Dominant Role of an Extended Asymmetric Four-Coordinated Water Network in the Hydrogen Evolution Reaction.

In situ and accurate measurement of the structure and dynamics of interfacial water in the hydrogen evolution reaction (HER) is a well-known challenge because of the coupling of water among varied structures and its dual role as reactants and solvents. Further, the interference of bulk water and intricate interfacial interactions always hinders the probing of interfacial water. Surface-enhanced infrared absorption spectroscopy is extremely sensitive for the measurement of interfacial water; herein, we develop a nanoconfinement strategy by introducing nonaqueous ionic liquids to decouple and tailor the water structure in the electric double layer and further combined with molecular dynamics simulations, successfully gaining the correlation between isolated water, water clusters, and the water network with HER activity. Our results clearly disclosed that the potential-dependent asymmetric four-coordinated water network, whose connectivity could be regulated by hydrophilic and hydrophobic cations, was positively correlated with HER activity, which provided a pioneering guidance framework for revealing the function of water in catalysis, energy, and surface science.

Single-Cell Genotyping of Single-Nucleotide Mutations Using In Situ Allele-Specific Loop-Mediated Isothermal Amplification.

Single-nucleotide mutations (SNMs) in the bacterial genome may cause antibiotic resistance. The visualization of SNMs can indicate antibiotic resistance phenotypes at the single-cell level but remains challenging. Herein, we proposed an in situ allele-specific isothermal amplification proceeded inside cells, allowing us to image bacterial genes with single-nucleotide resolution. The primer for loop-mediated isothermal amplification (LAMP) was designed with artificial mismatch bases to serve as an allele-specific probe, endowing LAMP to specifically amplify genes with SNMs. Due to the high amplification efficiency of LAMP, the method termed AlleLAMP can generate high gain for imaging SNMs and precisely quantify mutated quinolone-resistant Salmonella in bacterial mixture. We utilized AlleLAMP to survey the selection of antibiotic resistance under the preservative stress and found that the mutant quinolone-resistant strain owned a survival advantage over the wild-type quinolone-sensitive strain under the stress of preservatives. AlleLAMP can serve as a single-cell tool for analyzing the relationship between bacterial genotype and phenotype.

Cryptotanshinone-Doped Photothermal Synergistic MXene@PDA Nanosheets with Antibacterial and Anti-Inflammatory Properties for Wound Healing.

Humans are threatened by bacteria and other microorganisms, resulting in countless pathogen-related infections and illnesses. Accumulation of reactive oxygen species (ROS) in infected wounds activates strong inflammatory responses. The overuse of antibiotics has led to increasing bacterial resistance. Therefore, effective ROS scavenging and bactericidal capacity are essential and the advanced development of collaborative therapeutic techniques to combat bacterial infections is needed. Here, this work developes an MXene@polydopamine-cryptotanshinone (MXene@PDA-CPT) antibacterial nanosystem with excellent reactive oxygen and nitrogen species scavenging ability, which effectively inactivates drug-resistant bacteria and biofilms, thereby promoting wound healing. In this system, the adhesion of polydopamine nanoparticles to MXene produced a photothermal synergistic effect and free radical scavenging activity, presenting a promising antibacterial and anti-inflammatory strategy. This nanosystem causes fatal damage to bacterial membranes. The loading of cryptotanshinone further expanded the advantages of the system, causing a stronger bacterial killing effect and inflammation mitigatory effect with desired biosafety and biocompatibility. In addition, combining nanomaterials and active ingredients of traditional Chinese medicine, this work provides a new rationale for the future development of wound dressings, which contributes to eliminating bacterial resistance, delaying disease deterioration, and alleviating the pain of patients.

Revealing the Effect of Photothermal Therapy on Human Breast Cancer Cells: A Combined Study from Mechanical Properties to Membrane HSP70.

Hyperthermia-induced overexpression of heat shock protein 70 (HSP70) leads to the thermoresistance of cancer cells and reduces the efficiency of photothermal therapy (PTT). In contrast, cancer cell-specific membrane-associated HSP70 has been proven to activate antitumor immune responses. The dual effect of HSP70 on cancer cells inspires us that in-depth research of membrane HSP70 (mHSP70) during PTT treatment is essential. In this work, a PTT treatment platform for human breast cancer cells (MCF-7 cells) based on a mPEG-NH2-modified polydopamine (PDA)-coated gold nanorod core-shell structure (GNR@PDA-PEG) is developed. Using the force-distance curve-based atomic force microscopy (FD-based AFM), we gain insight into the PTT-induced changes in the morphology, mechanical properties, and mHSP70 expression and distribution of individual MCF-7 cells with high-resolution at the single-cell level. PTT treatment causes pseudopod contraction of MCF-7 cells and generates a high level of intracellular reactive oxygen species, which severely disrupt the cytoskeleton, leading to a decrease in cellular mechanical properties. The adhesion maps, which are recorded by aptamer A8 functional probes using FD-based AFM, reveal that PTT treatment causes a significant upregulation of mHSP70 expression and it starts to exhibit a partial aggregation distribution on the MCF-7 cell surface. This work not only exemplifies that AFM can be a powerful tool for detecting changes in cancer cells during PTT treatment but also provides a better view for targeting mHSP70 for cancer therapy.

Glutathione-Induced In Situ Michael Addition between Nanoparticles for Pyroptosis and Immunotherapy.

Most tumor treatments will fail when ignoring competition and cooperation between each cancer cell and its microenvironment. Inspired by game theory, therapeutic agents can be introduced to compete for intracellular molecules to disrupt the cooperation between molecules and cells. Biomineralized oxidized (-)-epigallocatechin-3-o-gallate (EGCG)-molybdenum ion coordination nanoparticles were prepared for disrupting redox equilibria and simultaneously reacting with intracellular GSH in a Michael addition to form large aggregates that can mechanically disrupt endosomal and plasma membranes, stimulating pyroptosis and anti-tumor immunological responses for versatile inhibition of different types of tumors. This design disrupts the cooperation between molecules and between cancer and immune cells, achieving an optimal payoff in competition and cooperation in cancer therapy.

Triazene-bridged energetic materials based on nitrotriazole: synthesis, characterization, and laser-ignited combustion performance.

Compared to the widely concerned azo bridges (-NN-), triazene bridges (-NN-NH-) with longer nitrogen chains are also favorable linking units leading to novel energetic materials. In this work, a new family of nitrogen-rich nitrotriazolate-based energetic compounds with a triazene bridge were synthesized and well characterized. The experimental results indicated that most of these new compounds have good thermal stabilities and low sensitivities. Among these, ammonium 5,5'-dinitro-3,3'-triazene-1,2,4-triazolate (3) and potassium 5-nitro-3,3'-triazene-1,2,4-triazolate (7) decomposed at a relatively high temperature (240.6 °C for 3 and 286.9 °C for 7). The impact sensitivities of the obtained compounds ranged from 15 J to 45 J. They also have relatively high positive heats of formation between 667.5 to 817.3 kJ mol-1. The calculated detonation pressures (P) were located between 23.7 and 34.8 GPa, and the calculated detonation velocities (D) were between 8011 and 9044 m s-1. Interestingly, ammonium 5-nitro-3,3'-triazene-1,2,4-triazolate (8) and hydroxylammonium 5-nitro-3,3'-triazene-1,2,4-triazole (10) possessed excellent laser-ignited combustion performance.

Revealing the Nanoarchitectonics of Amyloid ß-Aggregation on Two-Dimensional Biomimetic Membranes by Surface-Enhanced Infrared Absorption Spectroscopy.

The in vivo folding of amyloid ß (Aß) is influenced by many factors among which biomembrane interfaces play an important role. Here, using surface-enhanced infrared absorption (SEIRA) spectroscopy and atomic force microscopy (AFM), the adsorption, structure, and morphology of Aß42 aggregating on different two-dimensional interfaces were investigated. Results show that interfaces facilitate the aggregation of Aß42 and are conducive to the formation of homogeneous aggregates, while the aggregates vary on different interfaces. On hydrophobic interfaces, strong hydrophobic interactions with the C-terminus of Aß42 result in the formation of small oligomers with a small proportion of the ß-sheet structure. On hydrophilic interfaces, hydrogen-bonding interactions and electrostatic interactions promote the formation of large aggregate particles with ß-sheet structure. The hydration repulsion plays an important role in the interaction of Aß42 with interfaces. These findings help to understand the nature of Aß42 adsorption and aggregation on the biomembrane interface and the origin of heterogeneity and polymorphism of Aß42 aggregates.

Chirality-Dependent Dynamic Evolution of the Protein Corona on the Surface of Quantum Dots.

Elucidating the biological behavior of engineered nanoparticles, for example, the protein corona, is important for the development of safe and efficient nanomedicine, but our current understanding is still limited due to its highly dynamic nature and lack of adequate analytical tools. In the present work, we demonstrate the establishment of a fluorescence resonance energy transfer (FRET)-based platform for monitoring the dynamic evolution behavior of the protein corona in complex biological media. With human serum albumin and lysozyme as the model serum proteins, the protein exchange process of the preformed corona on the surface of chiral quantum dots (QDs) upon feeding either individual protein or human serum was monitored in situ by FRET. Important parameters characterizing the evolution process of protein corona could be obtained upon quantitative analysis of FRET data. Further combining real-time FRET monitoring with gel electrophoresis experiments revealed that the nature of the protein initially adsorbed on the surface of QDs significantly affects the subsequent dynamic exchange behavior of the protein corona. Furthermore, our results also revealed that only a limited proportion of proteins are involved in the protein exchange, and the exchange process exhibits a significant dependence on the surface chirality of QDs. This work demonstrates the feasibility of FRET as a powerful tool to exploit the dynamic evolution process of the protein corona, which can provide theoretical guidance for further design of advanced nanomaterials for biomedical applications.

Development of Nickel Selenide@polydopamine Nanocomposites for Magnetic Resonance Imaging Guided NIR-II Photothermal Therapy.

The penetration depth of near-infrared laser has greatly restricted the development of most photothermal agents. Recently, photothermal agents in the second near-infrared (NIR-II) window have drawn great attention as they can overcome above barrier. Herein, a novel "all in one" NIR-II responsive nanoplatform (nickel selenide @polydopamine nanocomposites, NiSe@PDA NCs) based on in situ coating the polydopamine (PDA) on the surface of biomineralized nickel selenide nanoparticles (NiSe NPs) for dual-model imaging-guided photothermal therapy is reported. Under the illumination of NIR-II laser (1064 nm), the photothermal conversion efficiency of NiSe@PDA NCs can reach 48.4%, which is higher than that of single NiSe NPs due to the enhanced molar extinction coefficient. In addition, because of the paramagnetic effect of NiSe NPs, the constructed NiSe@PDA NCs can be acted as T1 contrast agent for magnetic resonance imaging (MRI). Most importantly, the MRI contrast effect is enhanced with the coating of PDA layer due to the loose structure of PDA. Ultimately, both in vitro and in vivo experiments demonstrate that the developed NCs can achieve efficient MRI-guided photothermal therapy for treating malignant tumor. Therefore, the designed NiSe@PDA NCs with excellent features show great potential for clinical MRI-guided cancer therapy.

Precise Subcellular Organelle Targeting for Boosting Endogenous-Stimuli-Mediated Tumor Therapy.

Though numerous external-stimuli-triggered tumor therapies, including phototherapy, radiotherapy, and sonodynamic therapy have made great progress in cancer therapy, the low penetration depth of the laser, safety concerns of radiation, the therapeutic resistance, and the spatio-temporal constraints of the specific equipment restrict their convenient clinical applications. What is more, the inherent physiological barriers of the tumor microenvironment (TME), including hypoxia, heterogeneity, and high expression of antioxidant molecules also restrict the efficiency of tumor therapy. As a result, the development of nanoplatforms responsive to endogenous stimuli (such as glucose, acidic pH, cellular redox events, and etc.) has attracted great attention for starvation therapy, ion therapy, prodrug-mediated chemotherapy, or enzyme-catalyzed therapy. In addition, nanomedicines can be modified by some targeted units for precisely locating in subcellular organelles and boosting the destroying of tumor tissue, decreasing the dosage of nanoagents, reducing side effects, and enhancing the therapeutic efficiency. Herein, the properties of the TME, the advantages of endogenous stimuli, and the principles of subcellular-organelle-targeted strategies will be emphasized. Some necessary considerations for the exploitation of precision medicine and clinical translation of multifunctional nanomedicines in the future are also pointed out.

Molecular Nature of Structured Water in the Light-Induced Interfacial Capacitance Changes at the Bioelectric Interface.

Uncovering the function of structured water in the interfacial capacitance at the molecular level is the basis for the development of the concept and model of the electric double layer; however, the limitation of the available technology makes this task difficult. Herein, using surface-enhanced infrared absorption spectroscopy combined with electrochemistry, we revealed the contribution of the cleavage of loosely bonded tetrahedral water to the enhancement of model membrane capacitance. Upon further combination with ionic perturbation, we found that the interface hydrogen bonding environment in the stern layer was greatly significant for the light-induced cleavage of tetrahedral water and thus the conversion of optical signals into electrical signals. Our work has taken an important step toward gaining experimental insight into the relationship between water structure and capacitance at the bioelectric interface.

Near-Infrared Activation of Sensory Rhodopsin II Mediated by NIR-to-Blue Upconversion Nanoparticles.

Direct optical activation of microbial rhodopsins in deep biological tissue suffers from ineffective light delivery because visible light is strongly scattered and absorbed. NIR light has deeper tissue penetration, but NIR-activation requires a transducer that converts NIR light into visible light in proximity to proteins of interest. Lanthanide-doped upconversion nanoparticles (UCNPs) are ideal transducer as they absorb near-infrared (NIR) light and emit visible light. Therefore, UCNP-assisted excitation of microbial rhodopsins with NIR light has been intensively studied by electrophysiology technique. While electrophysiology is a powerful method to test the functional performance of microbial rhodopsins, conformational changes associated with the NIR light illumination in the presence of UCNPs remain poorly understood. Since UCNPs have generally multiple emission peaks at different wavelengths, it is important to reveal if UCNP-generated visible light induces similar structural changes of microbial rhodopsins as conventional visible light illumination does. Here, we synthesize the lanthanide-doped UCNPs that convert NIR light to blue light. Using these NIR-to-blue UCNPs, we monitor the NIR-triggered conformational changes in sensory rhodopsin II from Natronomonas pharaonis (NpSRII), blue light-sensitive microbial rhodospsin, by FTIR spectroscopy. FTIR difference spectrum of NpSRII was recorded under two different excitation conditions: (ⅰ) with conventional blue light, (ⅱ) with UCNP-generated blue light upon NIR excitation. Both spectra display similar spectral features characteristic of the long-lived M photointermediate state during the photocycle of NpSRII. This study demonstrates that NIR-activation of NpSRII mediated by UCNPs takes place in a similar way to direct blue light activation of NpSRII.

Specific "Unlocking" of a Nanozyme-Based Butterfly Effect To Break the Evolutionary Fitness of Chaotic Tumors.

Chaos and the natural evolution of tumor systems can lead to the failure of tumor therapies. Herein, we demonstrate that iridium oxide nanoparticles (IrOx ) possess acid-activated oxidase and peroxidase-like functions and wide pH-dependent catalase-like properties. The integration of glucose oxidase (GOD) unlocked the oxidase and peroxidase activities of IrOx by the production of gluconic acid from glucose by GOD catalysis in cancer cells, and the produced H2 O2 was converted into O2 to compensate its consumption in GOD catalysis owing to the catalase-like function of the nanozyme, thus resulting in the continual consumption of glucose and the self-supply of substrates to generate superoxide anion and hydroxyl radical. Moreover, IrOx can constantly consume glutathione (GSH) by self-cyclic valence alternation of IrIV and IrIII . These cascade reactions lead to a "butterfly effect" of initial starvation therapy and the subsequent pressure of multiple reactive oxygen species (ROS) to completely break the self-adaption of cancer cells.