A Novel Redox-Sensitive Drug Delivery System Based on Trimethyl-Locked Polycarbonate.

Stimuli-responsive polymer nanocarriers, capable of exploiting subtle changes in the tumor microenvironment for controlled drug release, have gained significant attention in cancer therapy. Notably, NAD(P)H: quinone oxidoreductase 1 (NQO1), found to be upregulated in various solid tumors, represents a promising therapeutic target due to its effective capability to enzymatically reduce trimethyl-locked (TML) benzoquinone structures in a physiological condition. In this study, a novel redox-sensitive carbonate monomer, MTC, was synthesized, and its amphiphilic block copolymers were prepared through ring-opening polymerization. By successfully self-assembling poly(ethylene glycol)-b-PMTC micelles, the model drug doxorubicin (DOX) was encapsulated with high efficiency. The micelles exhibited redox-responsive behavior, leading to rapid drug release. In vitro assessments confirmed their excellent biocompatibility and hemocompatibility. Furthermore, the inhibition of the NQO1 enzyme reduced drug release in NQO1-overexpressed cells but not in control cells, resulting in decreased cytotoxicity in the presence of NQO1 enzyme inhibitors. Overall, this study showcases the potential of MTC-based polycarbonate micelles to achieve targeted and specific drug release in the NQO1 enzyme-mediated tumor microenvironment. Therefore, the self-assembly of MTC-based polymers into nanomicelles holds immense promise as intelligent nanocarriers in drug delivery applications.

High-Entropy Alloys for Electrocatalysis: Design, Characterization, and Applications.

High-entropy alloys (HEAs) are expected to function well as electrocatalytic materials, owing to their widely adjustable composition and unique physical and chemical properties. Recently, HEA catalysts are extensively studied in the field of electrocatalysis; this motivated the authors to investigate the relationship between the structure and composition of HEAs and their electrocatalytic performance. In this review, the latest advances in HEA electrocatalysts are systematically summarized, with special focus on nitrogen fixation, the carbon cycle, water splitting, and fuel cells; in addition, by combining this with the characterization and analysis of HEA microstructures, rational design strategies for optimizing HEA electrocatalysts, including controllable preparation, component regulation, strain engineering, defect engineering, and theoretical prediction are proposed. Moreover, the existing issues and future trends of HEAs are predicted, which will help further develop these high-entropy materials.

Highly Tough, Stretchable, and Solvent-Resistant Cellulose Nanocrystal Photonic Films for Mechanochromism and Actuator Properties.

Cellulose nanocrystals (CNCs)-derived photonic materials have confirmed great potential in producing renewable optical and engineering areas. However, it remains challenging to simultaneously possess toughness, strength, and multiple responses for developing high-performance sensors, intelligent coatings, flexible textiles, and multifunctional devices. Herein, the authors report a facile and robust strategy that poly(ethylene glycol) dimethacrylate (PEGDMA) can be converged into the chiral nematic structure of CNCs by ultraviolet-triggered free radical polymerization in an N,N-dimethylformamide solvent system. The resulting CNC-poly(PEGDMA) composite exhibits impressive strength (42 MPa), stretchability (104%), toughness (31 MJ m-3 ), and solvent resistance. Notably, it preserves vivid optical iridescence, displaying stretchable variation from red, yellow, to green responding to the applied mechanical stimuli. More interestingly, upon exposure to spraying moisture, it executes sensitive actuation (4.6° s-1 ) and multiple complex 3D deformation behaviors, accompanied by synergistic iridescent appearances. Due to its structural anisotropy of CNC with typical left-handedness, the actuation shows the capability to generate a high probability (63%) of right-handed helical shapes, mimicking a coiled tendril. The authors envision that this versatile system with sustainability, robustness, mechanochromism, and specific actuating ability will open a sustainable avenue in mechanical sensors, stretchable optics, intelligent actuators, and soft robots.

High-Efficiency Phosphopeptide and Glycopeptide Simultaneous Enrichment by Hydrogen Bond-based Bifunctional Smart Polymer.

Aberrant protein phosphorylation and glycosylation are closely associated with a number of diseases. In particular, an interplay between phosphorylation and glycosylation regulates the hyperphosphorylation of protein tau, which is regarded as one of the pathologic features of Alzheimer's disease (AD). However, simultaneous characterization of these two types of post-translational modifications (PTMs) in the complex biological samples is challenging. TiO2 and the immobilized ion affinity chromatography (IMAC)-based enrichment method suffers from low selectivity and/or low recovery of phosphopeptides and glycopeptides because of the inherent limitations in intermolecular interactions. Here, we introduce a hydrogen bond-based poly[(N-isopropylacrylamide-co-4-(3-acryloylthioureido)benzoic acid0.2] (referred to as PNI-co-ATBA0.2) as a bifunctional enrichment platform to solve this bottleneck problem. Benefited from multiple hydrogen bonding interactions of ATBA with N-acetylneuraminic acid (Neu5Ac) located at the terminals of sialylated glycans and from favorable conformational transition of the copolymer chains, the smart copolymer has high adsorption capacity (370 mg·g-1) and high recovery (ranging from 74.1% ± 7.0% to 106% ± 5.0% (n = 3)) of sialylated glycopeptides. The smart copolymer also has high selectivity (79%) for simultaneous enrichment of glycopeptides and phosphopeptides from 50 µg HeLa cell lysates, yielding 721 unique phosphorylation sites from 631 phosphopeptides and 125 unique glycosylation sites from 120 glycopeptides. This study will open a new avenue and provide a novel insight for the design of enrichment materials used in PTM-proteomics.

The formation and accumulation of protein-networks by physical interactions in the rapid occlusion of laticifer cells in rubber tree undergoing successive mechanical wounding.

BACKGROUND: Although the wound response of plants has been extensively studied, little is known of the rapid occlusion of wounded cell itself. The laticifer in rubber tree is a specific type of tissue for natural rubber biosynthesis and storage. In natural rubber production, tapping is used to harvest the latex which flows out from the severed laticifer in the bark. Therefore, study of the rapid wound-occlusion of severed laticifer cells is important for understanding the rubber tree being protected from the continuously mechanical wounding. RESULTS: Using cytological and biochemical techniques, we revealed a biochemical mechanism for the rapid occlusion of severed laticifer cells. A protein-network appeared rapidly after tapping and accumulated gradually along with the latex loss at the severed site of laticifer cells. Triple immunofluorescence histochemical localization showed that the primary components of the protein-network were chitinase, ß-1,3-glucanase and hevein together with pro-hevein (ProH) and its carboxyl-terminal part. Molecular sieve chromatography showed that the physical interactions among these proteins occurred under the condition of neutral pH. The interaction of ß-1,3-glucanase respectively with hevein, chitinase and ProH was testified by surface plasmon resonance (SPR). The interaction between actin and ß-1,3-glucanase out of the protein inclusions of lutoids was revealed by pull-down. This interaction was pharmacologically verified by cytochalasin B-caused significant prolongation of the duration of latex flow in the field. CONCLUSIONS: The formation of protein-network by interactions of the proteins with anti-pathogen activity released from lutoids and accumulation of protein-network by binding to the cytoskeleton are crucial for the rapid occlusion of laticifer cells in rubber tree. The protein-network at the wounded site of laticifer cells provides not only a physical barrier but also a biochemical barrier to protect the wounded laticifer cells from pathogen invasion.

Preparation of MgAlFe-LDHs as a deicer corrosion inhibitor to reduce corrosion of chloride ions in deicing salts.

This material consists of a double hydroxide consisting of Mg, Al, Fe in a 9:2:1 M ratios, which was synthesised by hydrothermal method under constant pH conditions. The products were calcined at 500 °C for use as a deicing corrosion inhibitor, which breaks through the problem that the traditional corrosion inhibitor itself doesn't have the capability of deicing. The raw material of Al and Fe was extracted from the red mud by acid leaching. Characterization by XRD, FTIR, BET, XPS, SEM and TEM revealed that the interlaminar structure of the collapsed double-layered hydroxide material after high temperature calcination was regained by adsorbing Cl-. Cl- was filled between the layers of double hydroxide and existed by chemical adsorption. By measuring the freezing point of mixed deicing salt and the ability to melt snow and deicing, the freezing point of the inhibitor was found. When the solution concentration was 40 wt%, the freezing point of the mixed deicing salt reached -27.6 °C. Corrosion inhibitors can reduce the amount of CaCl2 when used in combination with anhydrous CaCl2. In addition, the determination of the corrosion rate of carbon steel and the resistance to salt freezing of concrete has revealed that the corrosion inhibitor can adsorb Cl- and reduce the content of free Cl- at low temperatures. Therefore, corrosion inhibitor plays a significant role in reducing the amount of Cl- used, the corrosion rate of carbon steel, and the salt-freezing resistance of concrete.

Reiterated Targeting Peptides on the Nanoparticle Surface Significantly Promote Targeted Vascular Endothelial Growth Factor Gene Delivery to Stem Cells.

Nonviral gene delivery vectors hold great promise for gene therapy due to the safety concerns with viral vectors. However, the application of nonviral vectors is hindered by their low transfection efficiency. Herein, in order to tackle this challenge, we developed a nonviral vector integrating lipids, sleeping beauty transposon system and 8-mer stem cell targeting peptides for safe and efficient gene delivery to hard-to-transfect mesenchymal stem cells (MSCs). The 8-mer MSC-targeting peptides, when synthetically reiterated in three folds and chemically presented on the surface, significantly promoted the resultant lipid-based nanoparticles (LBNs) to deliver VEGF gene into MSCs with a high transfection efficiency (∼52%) and long-lasting gene expression (for longer than 170 h) when compared to nonreiterated peptides. However, the reiterated stem cell targeting peptides do not enable the highly efficient gene transfer to other control cells. This work suggests that the surface presentation of the reiterated stem cell-targeting peptides on the nonviral vectors is a promising method for improving the efficiency of cell-specific nonviral gene transfection in stem cells.

Metal-Organic Frameworks Meet Polymers: From Synthesis Strategies to Healthcare Applications.

Metal-organic frameworks (MOFs) have been at the forefront of nanotechnological research for the past decade owing to their high porosity, high surface area, diverse configurations, and controllable chemical structures. They are a rapidly developing class of nanomaterials that are predominantly applied in batteries, supercapacitors, electrocatalysis, photocatalysis, sensors, drug delivery, gas separation, adsorption, and storage. However, the limited functions and unsatisfactory performance of MOFs resulting from their low chemical and mechanical stability hamper further development. Hybridizing MOFs with polymers is an excellent solution to these problems, because polymers-which are soft, flexible, malleable, and processable-can induce unique properties in the hybrids based on those of the two disparate components while retaining their individuality. This review highlights recent advances in the preparation of MOF-polymer nanomaterials. Furthermore, several applications wherein the incorporation of polymers enhances the MOF performance are discussed, such as anticancer therapy, bacterial elimination, imaging, therapeutics, protection from oxidative stress and inflammation, and environmental remediation. Finally, insights from the focus of existing research and design principles for mitigating future challenges are presented.

Broad-Spectrum Clearance of Lipopolysaccharides from Blood Based on a Hemocompatible Dihistidine Polymer.

Blood infection can release toxic bacterial lipopolysaccharides (LPSs) into bloodstream, trigger a series of inflammatory reactions, and eventually lead to multiple organ dysfunction, irreversible shock, and even death, which seriously threatens human life and health. Herein, a functional block copolymer with excellent hemocompatibility is proposed to enable broad-spectrum clearance of LPSs from whole blood blindly before pathogen identification, facilitating timely rescue from sepsis. A dipeptide ligand of histidine-histidine (HH) was designed as the LPS binding unit, and poly[(trimethylamine N-oxide)-co-(histidine-histidine)], a functional block copolymer combining the LPS ligand of HH and a zwitterionic antifouling unit of trimethylamine N-oxide (TMAO), was then designed by reversible addition-fragmentation chain transfer (RAFT) polymerization. The functional polymer achieved effective clearance of LPSs from solutions and whole blood in a broad-spectrum manner and had good antifouling and anti-interference properties and hemocompatibility. The proposed functional dihistidine polymer provides a novel strategy for achieving broad-spectrum clearance of LPSs, with potential applications in clinical blood purification.

ChatGPT for shaping the future of dentistry: the potential of multi-modal large language model.

The ChatGPT, a lite and conversational variant of Generative Pretrained Transformer 4 (GPT-4) developed by OpenAI, is one of the milestone Large Language Models (LLMs) with billions of parameters. LLMs have stirred up much interest among researchers and practitioners in their impressive skills in natural language processing tasks, which profoundly impact various fields. This paper mainly discusses the future applications of LLMs in dentistry. We introduce two primary LLM deployment methods in dentistry, including automated dental diagnosis and cross-modal dental diagnosis, and examine their potential applications. Especially, equipped with a cross-modal encoder, a single LLM can manage multi-source data and conduct advanced natural language reasoning to perform complex clinical operations. We also present cases to demonstrate the potential of a fully automatic Multi-Modal LLM AI system for dentistry clinical application. While LLMs offer significant potential benefits, the challenges, such as data privacy, data quality, and model bias, need further study. Overall, LLMs have the potential to revolutionize dental diagnosis and treatment, which indicates a promising avenue for clinical application and research in dentistry.

Control of chloride ion corrosion by MgAlOx/MgAlFeOx in the process of chloride deicing.

Adding a corrosion inhibitor to the chloride deicing salt can prevent the corrosion and pollution of Cl-, which is very important. Layered double hydroxide (LDHs), calcined at high temperature is used as adsorbents to remove various anionic contaminants, and it can reduce the freezing point of solution after adsorbing anions. Therefore, this paper reports the use of calcined LDHs as corrosion inhibitors in deicing salts, which are denoted as MgAlOx or MgAlFeOx depending on the preparation element. By analyzing the removal efficiency and the freezing point of MgAlOx and MgAlFeOx to Cl-, the feasibility of the study was determined. Resulted that the removal efficiency to Cl- of MgAlFeOx at low temperature (0 ± 2 °C) and room temperature (25 ± 2 °C) was higher than that of MgAlOx, reaching 39.4% and 85.60%, respectively. And the freezing point of MgAlFeOx was lower than that of MgAlOx, the value was -12.0 °C. At the same time, we also found that CaCl2-MgAlOx and CaCl2-MgAlFeOx significantly reduced the corrosion of carbon steel and concrete compared with chloride salts, and CaCl2-MgAlFeOx had the lowest corrosion degree. Hence, MgAlFeOx was chosen as the corrosion inhibitor in chloride deicing salt. The metal molar ratio, synthesis temperature, and calcination temperature for preparation of MgAl/MgAlFe-LDHs were determined by XRD and TG-DSC analysis that were 9/2/1, 120 °C, and 500 °C, respectively. Characterization methods such as Zeta, XRD, XPS, BET, and SEM were used to study in detail the characteristic changes of MgAlFe-LDHs and MgAlFeOx after Fe3+ was added, and the mechanism of corrosion inhibitors was further determined that was achieved by adsorption and neutralization.

Ultrasmall Alloy Nanozyme for Ultrasound- and Near-Infrared Light-Promoted Tumor Ablation.

The therapeutic effect of chemodynamic therapy (CDT) is significantly restricted by the stern reaction conditions and slow reaction rate of the Fenton reaction (pH 3-4). Herein, we report an ultrasmall trimetallic (Pd, Cu, and Fe) alloy nanozyme (PCF-a NEs) possessing dynamic active-site synergism, thus exhibiting a cascade glutathione peroxidase and peroxidase (POD) mimicking activities in circumneutral pH. PCF-a NEs exhibit photothermally augmented POD property and high photothermal conversion efficiency (62%) for synergistic tumor cell apoptosis. In addition, ultrasound can also enhance the mass transfer at active catalytic sites of PCF-a NEs, in turn accelerating Fenton-like reaction for tumor-specific CDT. This work provides a strategy for engineering alloy nanozymes in a bioinspired way for the amplification of intratumor reactive oxygen species in response to external stimuli, demonstrating enhanced efficiency for the inhibition of tumor growth in vitro and in vivo.

Self-assembled semiconducting polymer based hybrid nanoagents for synergistic tumor treatment.

There is an impending need for the development of carrier-free nanosystems for single laser triggered activation of phototherapy, as such approach can overcome the drawbacks associated with irradiation by two distinct laser sources for avoiding prolonged treatment time and complex treatment protocols. Herein, we developed a self-assembled nanosystem (SCP-CS) consisting of a new semiconducting polymer (SCP) and encapsulated ultrasmall CuS (CS) nanoparticles. The SCP component displays remarkable near infrared (NIR) induced photothermal ability, enhanced reactive oxygen species (ROS) generation, and incredible photoacoustic (PA) signals upon activation by 808 nm laser for phototherapy mediated cancer ablation. The CuS component improves the PA imaging ability of SCP-CS, and also enhances photo-induced chemodynamic efficacy. Attributed to promoted single laser-triggered hyperthermia and enhanced ROS generation, the SCP-CS nanosystem shows effective intracellular uptake and intratumoral accumulation, enhanced tumor suppression with reduced treatment time, and devoid of any noticeable toxicity.

Bacterial Vesicle-Cancer Cell Hybrid Membrane-Coated Nanoparticles for Tumor Specific Immune Activation and Photothermal Therapy.

Cell membrane camouflaged nanoparticles (NPs) have been increasingly explored to leverage natural cellular functions and adapt to various biomedical applications. Herein, we report an OMV-CC hybrid membrane, which consists of a bacterial outer membrane vesicle (OMV) and B16-F10 cancer cell (CC) membrane, and successfully coat it onto hollow polydopamine (HPDA) NPs. We harness the advantage of OMV immunotherapy together with HPDA-mediated photothermal therapy (PTT) to improve the antitumor efficacy toward melanoma. When injected intravenously via the tail vein, HPDA@[OMV-CC] NPs homogeneously target melanoma and activate the immune response by rapidly stimulating dendritic cell (DC) maturation in lymph nodes in the vaccinated mice. Our results show that the antitumor immune response and PTT reciprocally potentiate the therapeutic ability and fully eradicate melanoma without notable adverse effects. The homogeneous-target and immune activation hybrid biomimetic membrane provides the adaptability to various synergistic therapeutic and imaging applications by incorporating payload with application-specific functions.

cAMP sensitive nanochannels driven by conformational transition of a tripeptide-based smart polymer.

Inspired by biological nanochannels, a novel cyclic 3',5'-adenosine monophosphate (cAMP)-regulated artificial nanochannel based on a tripeptide Arg-Thr-Ala (RTA) design is developed. Highly specific binding between the tripeptide and cAMP triggers an obvious conformational transition of a smart polymer chain from a contracted state to a swollen one, which leads to a dynamic modulation of the gating behaviours of the nanochannels.

Self-assembled single-atom nanozyme for enhanced photodynamic therapy treatment of tumor.

Hypoxia of solid tumor compromises the therapeutic outcome of photodynamic therapy (PDT) that relies on localized O2 molecules to produce highly cytotoxic singlet oxygen (1O2) species. Herein, we present a safe and versatile self-assembled PDT nanoagent, i.e., OxgeMCC-r single-atom enzyme (SAE), consisting of single-atom ruthenium as the active catalytic site anchored in a metal-organic framework Mn3[Co(CN)6]2 with encapsulated chlorin e6 (Ce6), which serves as a catalase-like nanozyme for oxygen generation. Coordination-driven self-assembly of organic linkers and metal ions in the presence of a biocompatible polymer generates a nanoscale network that adaptively encapsulates Ce6. The resulted OxgeMCC-r SAE possesses well-defined morphology, uniform size distribution and high loading capacity. When conducting the in situ O2 generation through the reaction between endogenous H2O2 and single-atom Ru species of OxgeMCC-r SAE, the hypoxia in tumor microenvironment is relieved. Our study demonstrates a promising self-assembled nanozyme with highly efficient single-atom catalytic sites for cancer treatment.

A Mesoporous Nanoenzyme Derived from Metal-Organic Frameworks with Endogenous Oxygen Generation to Alleviate Tumor Hypoxia for Significantly Enhanced Photodynamic Therapy.

Tumor hypoxia compromises the therapeutic efficiency of photodynamic therapy (PDT) as the local oxygen concentration plays an important role in the generation of cytotoxic singlet oxygen (1 O2 ). Herein, a versatile mesoporous nanoenzyme (NE) derived from metal-organic frameworks (MOFs) is presented for in situ generation of endogenous O2 to enhance the PDT efficacy under bioimaging guidance. The mesoporous NE is constructed by first coating a manganese-based MOFs with mesoporous silica, followed by a facile annealing process under the ambient atmosphere. After removing the mesoporous silica shell and post-modifying with polydopamine and poly(ethylene glycol) for improving the biocompatibility, the obtained mesoporous NE is loaded with chlorin e6 (Ce6), a commonly used photosensitizer in PDT, with a high loading capacity. Upon the O2 generation through the catalytic reaction between the catalytic amount NE and the endogenous H2 O2 , the hypoxic tumor microenvironment is relieved. Thus, Ce6-loaded NE serves as a H2 O2 -activated oxygen supplier to increase the local O2 concentration for significantly enhanced antitumor PDT efficacy in vitro and in vivo. In addition, the NE also shows T2 -weighted magnetic resonance imaging ability for its in vivo tracking. This work presents an interesting biomedical use of MOF-derived mesoporous NE as a multifunctional theranostic agent in cancer therapy.

Magnetic Zn (II) ion-imprinted polymer prepared by the surface imprinting technique and its adsorption properties.

A novel magnetic Zn (II) ion-imprinted polymer was prepared by the surface ion-imprinted technique by using magnetic Fe3O4@SiO2 microspheres as supporter, methacrylic acid and salicylaldoxime as monomers, ethylene glycol dimethacrylate as the crosslinker. The products were characterized by Fourier transform infrared, X-ray photoelectron spectrometer, vibrating sample magnetometer and scanning electron microscope. The adsorption experiments showed that the imprinted polymer was employed successfully in comparison with non-imprinted polymer. When the temperature was in a range of 291-297 K, the maximum adsorption was about 52.69 mg g(-1) with an optimal pH 6.0 for an equilibrium time of 40 min. The imprinted polymer possessed high selectivity and specific recognition towards Zn (II). The Langmuir adsorption model was more favourable than the Freundlich or the Temkin adsorption model. Thermodynamic experiment showed that the adsorption was a spontaneous and endothermic process for Zn (II). The mechanism for Zn (II) adsorption on the imprinted polymer was investigated.

Preparation of a camptothecin prodrug with glutathione-responsive disulfide linker for anticancer drug delivery.

We present here a novel camptothecin (CPT) prodrug based on polyethylene glycol monomethyl ether-block-poly(2-methacryl ester hydroxyethyl disulfide-graft-CPT) (MPEG-SS-PCPT). It formed biocompatible nanoparticles (NPs) with diameters of approximately 122 nm with a CPT loading content as high as approximately 25 wt% in aqueous solution. In in vitro release studies, these MPEG-SS-PCPT NPs could undergo triggered disassembly and much faster release of CPT under glutathione (GSH) stimulus than in the absence of GSH. The CPT prodrug had high antitumor activity, and another anticancer drug, doxorubicin hydrochloride (DOX⋅HCl), could also be introduced into the prodrug with a high loading amount. The DOX·HCl-loaded CPT prodrug could deliver two anticancer drugs at the same time to produce a collaborative cytotoxicity toward cancer cells, which suggested that this GSH-responsive NP system might become a promising carrier to improve drug-delivery efficacy.

Fabrication of single-hole glutathione-responsive degradable hollow silica nanoparticles for drug delivery.

In the present study, a kind of single-hole glutathione (GSH)-responsive degradable hollow silica nanoparticles (G-DHSNs) was synthesized and used as carriers of doxorubicin (DOX) (DOX-G-DHSNs). The G-DHSNs were accurately designed and fabricated with a simple and convenient method, and without any extra pernicious component. The composition, morphology and properties of the G-DHSNs had been characterized by (1)HNMR spectra, Fourier transform infrared spectrograph, thermo gravimetric analysis, transmission electron microscope, and scanning electron microscope. The degradation study of G-DHSNs showed that the G-DHSNs would be broken into pieces after interacting with GSH. Besides, the negligible hemolytic activity and low cytotoxicity of the G-DHSNs demonstrated its excellent biocompatibility. pH- and GSH-triggered release of DOX followed by the decomposition of G-DHSNs within TCA8113 cancer cells was further confirmed by flow cytometry and confocal laser scanning microscopy studies. All of these results indicated that G-DHSNs can be used as safe and promising drug nanocarriers.