To overcome the instability of astaxanthin (AST) during processing and gastrointestinal delivery, this study developed a multifunctional nanocarrier through the precise self-assembly of lipid bilayers that incorporated d-α-tocopherol polyethylene glycol 1000 succinate, a widely used biocompatible surfactant known as TPGS. Multidimensional characterization results demonstrated that the incorporation of TPGS formed a stable hydration layer, contributing to the distinctive mushroom-cloud-like architecture on the liposome surface. Spectroscopic analysis confirmed that the hydrophobic segment of TPGS was effectively embedded into the lipid membrane through intermolecular forces, while the hydrophilic segment formed an orderly arranged structure at the interface. Interfacial analysis revealed that low-concentration TPGS formed an ordered monolayer through a membrane-anchoring strategy, thereby assembling into a three-dimensional protective architecture on the liposome interface. This structure significantly enhanced transepithelial transport and antioxidant activity, while also demonstrating excellent biosafety in subsequent in vitro assays. This study presents an innovative and robust delivery system for AST through molecular-level interface engineering, advancing the application of functional amphiphilic polymers in the field of precision nutrient delivery.

Rationale: Radiotherapy is a principal modality in cancer treatment, effectively controlling local tumor growth and possessing the potential to enhance the immunogenicity of tumor cells, thereby improving the antitumor immunity. However, its efficacy is often limited by insufficient production of reactive oxygen species (ROS), tumor hypoxia, and the immunosuppressive tumor microenvironment (TME). Therefore, developing strategies to amplify ROS and reshaping the hypoxic, immunosuppressive TME is crucial for advancing radiotherapy. Methods: In this study, we designed a polyethylene glycol (PEG)-modified gold@manganese dioxide core-shell nanoparticle (GMCN@PEG) that is responsive to the acidic TME. We then investigated its ability to enhance radiotherapy and magnetic resonance-computed tomography (MR-CT) dual-modality imaging both in vivo and in vitro. Results: GMCN@PEG exhibits good biocompatibility under neutral physiological conditions and, upon exposure to the acidic TME, it alleviates tumor hypoxia and amplifies ROS production. This leads to enhanced radiotherapy sensitivity and the induction of immunogenic cell death (ICD). Furthermore, GMCN@PEG activates the cGAS-STING signaling pathway, promoting dendritic cells (DCs) maturation, macrophages M1 polarization, and T cells infiltration, effectively counteracting the immunosuppressive state within the TME. Additionally, GMCN@PEG enhances dual-modality imaging through MR-CT, achieving the integration of diagnosis and therapy. Conclusion: In summary, GMCN@PEG as a multifunctional nanosensitizer, demonstrate significant potential and promise in improving the efficacy of radiotherapy, reshaping the tumor microenvironment, promoting antitumor immunity, and biomedical imaging enhancement.

This study addressed the critical challenge of the limited dissolved oxygen in traditional photoelectro & hybull; chemical enzyme biosensors by proposing a construction strategy for a "solid-liquid-gas three-phase enzymatic reaction interface", utilizing a three-dimensional(3D) dendritic nanostructure. The methodology involved the preparation of titanium dioxide(TiO2) nanowire arrays featuring a 3D dendritic structure on fluorine-doped tin oxide conductive glass through a two-step hydrothermal process. Following selective hydrophobic and hydrophilic treatments, along with enzyme modification, a stable three-phase interface was successfully established. This innovative design facilitates the direct transport of oxygen to the catalytic sites via the gas phase, effectively addressing the limitations associated with insufficient oxygen supply at the conventional solid-liquid two-phase interface. Experimental results demonstrate that the linear detection range of this sensor has been enhanced by a factor of 20 compared to traditional structures, while exhibiting excellent stability(relative standard deviation<2%). This research introduces a novel construction strategy for the development of highly sensitive and stable photoelectro & hybull; chemical sensors, which may significantly contribute to the early diagnosis of chronic diseases.

Background:Cell-penetrating peptides (CPPs) are considered ideal carriers for the delivery of drugs through the cell membrane barrier, with enhanced permeation and retention effects. These peptides can increase the bioavailability of drugs and reduce their side effects. In this study, we developed a polypeptide called "cell-penetrating peptide (KRP)", linked it with doxorubicin (DOX), and created a pH-responsive triggered drug delivery system called "KRP-Hyd-DOX". Methods:We generated KRP through the application of standard Fmoc solid-phase peptide synthesis (SPPS). We attached DOX through a stable amide bond, using 3-maleimidopropionic acid as a linker, yielding KRP-DOX. With 6-maleimidopropionic acid as a linker, we connected DOX via a pH-sensitive hydrazone bond, resulting in KRP-Hyd-DOX. The pH-responsive drug-release performance of KRP-Hyd-DOX was evaluated through the calculation of the cumulative release of DOX at various time intervals and under different pH conditions via the DOX standard curve in the corresponding buffer. The cell penetration and cytotoxicity of KRP-Hyd-DOX, KRP-DOX, and DOX-hydrochloride (HCL) were compared. Results:The efficiency of KRP-DOX and KRP-Hyd-DOX in releasing free DOX was approximately 30% after 24 hours under pH 7.4. Under pH 5.0, the efficiency of KRP-DOX in releasing free DOX did not change significantly as compared to that at pH 7.4, while the efficiency of KRP-Hyd-DOX in releasing free DOX increased to 65% after 24 hours. After 24-hour exposure to KRP-Hyd-DOX, KRP-DOX, and DOX-HCL across different concentrations, MG63 cell viability exhibited a dose-dependent decline. The half-maximal inhibitory concentration (IC50) of KRP-Hyd-DOX (MG63 cells/5.22 µM) was less than that of KRP-DOX (MG63 cells/7.41 µM). Conclusions:The system we created (KRP-Hyd-DOX) leverages the synergistic effect of KRP and DOX, enhancing efficacy while minimizing side effects.

The accurate determination of hydrogen peroxide (H2O2), an important clinical disease relevant biomarker, is of great importance for the diagnosis and management of illnesses. By using the cathodic monitoring approach, H2O2 can be accurately detected because interfering signals from easily oxidizable endogenous and exogenous species in biofluids can be avoided. However, the simultaneous occurrence of the oxygen reduction reaction (ORR) restricts the practical use of this cathodic method. In this study, via oxygen vacancy modulation, we synthesized FeOx catalysts that can selectively reduce H2O2 over O-2. The H2O2 detection system based on this catalyst exhibits an outstanding ORR inhibition ability. Furthermore, by integrating this catalyst with glucose oxidase, a model enzyme, a reliable bioassay system was developed that can selectively detect glucose over a wide variety of interferents in artificially simulated tissue fluids. The bioassay system employing this catalyst in conjunction with oxidases is generally applicable to accurate detect a wide range of biomarkers.

As a p-type semiconductor, layered SnSe has attracted more and more attention because of its great potential application in the field of optoelectronics. However, the strong phonon scattering caused by abundant intrinsic vacancy defects dramatically reduces the performance of carrier transport. It is significant to effectively compensate for the intrinsic defects and reduce the phonon scattering for photodetection materials. In this letter, a novel and simple method is used to reduce the scattering and thus improve the detector performance. The inhibition effect of doping on phonon scattering is systematically studied by experiments and theoretical calculations. The Bi-doped SnSe photodetector exhibits great responsivities of 2.13 A W-1 (447 nm), 1.35 A W-1 (655 nm) and 1.91 A W-1 (980 nm) at 5 V, which are about 2 similar to 3 folds better than those of the undoped device. Furthermore, for the Bi-doped SnSe photodetector, the I-on/I-off are about 46.7, 20.3 and 30.3 for 447 nm, 655 nm and 980 nm, respectively, which are much higher than those of the SnSe photodetector. The photoluminescence and absorption are performed to confirm the bandgap and defects energy level. Meanwhile, the temperaturedependent current-voltage curves measurement is utilized to prove that the enhancement in response performance is because of the decrease in intensity of phonon scattering, which is attributed to the reduction of scattering centers and the weakening of the effect of vacancy defects on the structural translational asymmetry. All these results evidently illustrate that adjustment in phonon scattering is an effective way to achieve highperformance SnSe photodetectors.

Oxidase enzyme-based electrochemical bioassays have garnered considerable interest due to their specificity and high efficiency. However, in traditional solid-liquid diphase enzyme electrode systems, the low solubility of oxygen and its slow mass transfer rate limit the oxidase catalytic reaction kinetics, thereby affecting the bioassay performance, including the detection accuracy, sensitivity, and linear dynamic range. ZIF-8 nanoparticles (NPs) possess hydrophobic and high-porosity characteristics, enabling them to serve as oxygen nanocarriers. In this work, we constructed a solid-liquid-air triphase enzyme electrode by encapsulating ZIF-8 NPs within an oxidase network. Hydrophobic ZIF-8 NPs can provide a rapid and sufficient supply of oxygen for the oxidase-catalyzed reactions, which enhances and stabilizes the kinetics of oxidase-catalyzed reactions. This approach eliminates the issue of "oxygen deficiency" at the traditional solid-liquid diphase interface. Consequently, the triphase enzyme electrode exhibits a 12-fold higher linear detection range than the diphase system and possesses good detection accuracy in electrolytes even with fluctuating oxygen levels. This work proposes a novel approach to construct triphase reaction systems for addressing the gas deficiency problem in heterogeneous catalysis.

Liver cancer is the third leading cause of cancer deaths globally. The use of Hydroxycamptothecin (HCPT) as a first-line chemotherapeutic agent for liver, lung, and gastric cancers is often hampered by its low activity, limited targeting, and poor water solubility. This results in a low accumulation of HCPT in tumor cells, as well as the inability to maintain continuous treatment. Consequently, there is an urgent need to develop an accessory method that can enhance the therapeutic efficacy of HCPT while exhibiting good biocompatibility and targeted delivery ability. To address this critical issue, an enzyme-triggered supramolecular nanocarrier, refer as SCD/LCC SNCs, has been successfully developed, leveraging the aggregation of the negatively charged sulfate-modified β-CDs and positively charged lauroylcholine chloride (LCC). This nanocarrier demonstrates acetylcholinesterase (LCC) triggered decomposition behavior, making it a promising drug carrier for HCPT. The cellular assays conducted have demonstrated that HCPT loaded into these SCD/LCC SNCs exhibit reduced cytotoxicity towards normal cells while maintaining robust tumor inhibitory activity and inducing apoptosis. Therefore, this study offers a promising strategy for the effective use of HCPT in the treatment of liver cancer.

Bioassay systems that can selectively detect biomarkers at both high and low levels are of great importance for clinical diagnosis. In this work, we report an enzyme electrode with an oxygen reduction reaction (ORR)-tolerant H2O2 reduction property and an air-liquid-solid triphase interface microenvironment by regulating the surface defects and wettability of nanoporous tin oxide (SnOx). The enzyme electrode allows the oxygen that is required for the oxidase catalytic reaction to be transported from the air phase to the reaction zone, which greatly enhances the enzymatic kinetics and increases the linear detection upper limit. Meanwhile, the ORR-tolerant H2O2 reduction property of SnOx catalysts achieved via oxygen vacancy engineering greatly reduces the interferent signals caused by oxygen and various easily oxidizable endogenous/exogenous species, which enables the selective detection of biomarkers at trace levels. The synergistic effect between these two novel qualities features a bioassay system with a wide dynamic linear range and high selectivity for the accurate detection of a wide range of biomarkers, such as glucose, lactic acid, uric acid, and galactose, offering the potential for reliable clinical diagnosis applications.

The enzymatic reaction system with a solid-liquid-gas three-phase interface microenvironment allows oxygen to be directly supplied to the oxidase catalytic reaction from the gas phase, effectively improving enzyme kinetics as compared with the conventional two-phase system. For this new system, a mathematical model is developed in this work to describe the enzymatic reaction coupled with interphase mass transfer, by which the influences of three-phase interfacial microenvironment on reaction kinetics can be systematically and quantitatively explored. The numerical simulations reveal that the flux of oxygen transport across the interface between the gas phase and the enzyme layer dominantly determines the H2O2 production rate. The porous substrate possessing larger porosity and smaller pores, when coated with a thick and concentrated enzyme layer, can potentially lead to higher oxygen supply and hence a higher H2O2 production rate. Moreover, regardless of the pore diameter, the H2O2 production rate remains constant after the porosity is greater than 0.8, and if the enzyme concentration is not less than 5 mol m-3, the H2O2 production rate no longer changes after the thickness of the enzyme layer is greater than 0.5 mu m. This work offers a powerful in silico tool for the investigation of the three-phase enzymatic reaction system. The quantitative results and mechanistic findings will lead to optimized design of this promising system.

In the field of biomolecule detection, self-powered photoelectrochemical (PEC) bioassay devices have gained considerable interest with no demand for an external voltage but rather solar energy consumption. In this study, we present a self-powered PEC bioassay system that consists of a nanoporous BiVO4 photoanode coupled to a biophotocathode with a solidliquidair triphase oxidase enzymatic interface. The triphase biophotocathode was assembled by immobilizing oxidase on superhydrophobic Cu2O@TiO2 nanowire arrays. A high and steady interfacial oxygen concentration can be ensured by the triphase biophotocathode with much increased gas mass transport capability, which consequently enhance the kinetics of the oxidase enzymatic reaction as well as the sensing performance of self-powered PEC bioassay system. For the diphase biophotocathode based system, the low solubility and slow diffusion rate of oxygen restrict the kinetics of the oxidase catalytic reaction. As a result, the proposed triphase self-powered PEC bioassay platform exhibits excellent performance with a linear range up to 20 mM for glucose (a model analyst) detection, which is 20 times higher than that of the diphase one. Furthermore, an exceptional anti-interface is obtained by the cathodic bioanalysis approach in the self-powered PEC bioassay system.

AbstractAs a typical superwettability behavior, superhydrophobicity can provide an appropriate strategy to enhance the mass transport in multiphase chemical reactions. In the oxidase‐based enzymatic reactions, the elaborately regulating of reactant oxygen are critical to the development of an oxidase‐based high‐performance biosensor. In solid–liquid diphase condition, however, the kinetics of oxidase‐catalyzed reactions is inhibited by delayed mass transport and poor solubility of oxygen. To address this limitation, the design of the solid–liquid–air triphase interface is proposed according to the binary cooperation of superhydrophobicity and hydrophilicity. On the triphase joint interface, oxygen required for the oxidase‐catalyzed reactions can diffuse directly to the reaction center from the air phase through the micro/nanostructured superhydrophobic substrate, thus improving the kinetics of the oxidase‐catalyzed reactions. In this minireview, we summarize recent advances in the fabrication of triphase reaction system based on different superhydrophobic substrate for oxidase‐based biosensors. Common substrates including fibrous network, nanowire arrays, 3D porous framework, and hollow sphere structures are outlined in categories.

Electrochemical bioassays based on oxidase reactions are frequently used in biological sciences and medical industries. However, the enzymatic reaction kinetics are severely restricted by the poor solubility and slow diffusion rate of oxygen in conventional solid-liquid diphase reaction systems, which inevitably compromises the detection accuracy, linearity, and reliability of the oxidase-based bioassay. Herein, an effective solid-liquid-air triphase bioassay system is provided that uses hydrophobic hollow carbon spheres (HCSs) as oxygen nanocarriers. The oxygen stored in the cavity of HCS can rapidly diffuse to the oxidase active sites through the mesoporous carbon shell, providing sufficient oxygen for oxidase-based enzymatic reactions. As a result, the triphase system can significantly improve the enzymatic reaction kinetics and obtain a 20-fold higher linear detection range than the normal diphase system. Other biomolecules can also be determined using this triphase technique, and the triphase design strategy offers a new route to address the gas deficiency problem in catalytic reactions that involve gas consumption.

Abnormal hydrogen peroxide (H2O2) levels in the cellular environment are closely related to cell dysfunction and serious diseases. Thus, selective and sensitive H2O2 detections are urgently needed for clinical diagnosis and therapy. Herein, via surface defect engineering, an oxygen‐tolerant electrocatalyst based on tin oxide for selective H2O2 reduction and detection with exceptional stability and activity is designed and developed. When introduced at an appropriate level (≈5.3%), surface oxygen vacancies help lower the charge transfer resistance for enhancing the H2O2 reduction reaction, while maintain the weak oxygen (O2) adsorption, which enables a constant H2O2 reduction (sensing) response in the electrolyte at variable oxygen levels. Moreover, the tin oxide‐based assay system exhibits outstanding stability over a wide pH range of 4–9, as well as selectivity in the presence of interferent endogenous and exogenous electroactive species, which is suitable for trace H2O2 monitoring secreted from NB4 cells, a model cancer cell. The oxygen vacancy‐mediated tin oxide achieves the highest stability as well as high selectivity compared to reported electrochemical probes for specific H2O2 detection in biological environments, with the potential for biological and biomedical applications.

Developing photoelectrochemical (PEC) bioassays based on the principle of a photocathodic measurement of enzymatic product H2O2 is highly attractive because it can naturally avoid interfering signa...

Coupling the oxidase enzymatic and H 2 O 2 cathodic reactions is an ideal approach for accurate bioassays development because it naturally avoids most endogenous/exogenous electroactive interferents in biofluids. However, the accompanying oxygen cathodic reaction at the surface of commonly used stable catalysts compromises the bioassay accuracy, thus limiting practical application of this detection principle. Here, highly active oxygen‐insensitive electrocatalysts for H 2 O 2 reduction by modifying noble metals (Pt, Au) with an ultra‐thin tin oxide layer that can selectively block the diffusion of oxygen from the electrolyte to the noble metal surface, are reported. This empowers the electrocatalysts with enhanced resistance to current interference from oxygen reduction reaction, thus enabling highly selective sensing of sarcosine, a model analyte (a biomarker for prostate cancer), in the presence of various electroactive interferences. This work highlights the importance of H 2 O 2 cathodic reactions in accurate biomarker detection and their advanced applications in life science, including developing reliable biomarker assays.

The accurate detection of H2O2 is crucial in oxidase-based cathodic photoelectrochemical enzymatic bioanalysis but will be easily compromised in the conventional photoelectrode-electrolyte diphase system due to the fluctuation of oxygen levels and the similar reduction potential between oxygen and H2O2. Herein, a solid-liquid-air triphase bio-photocathode based on a superhydrophobic three-dimensional (3D) porous micro-nano-hierarchical structured CuxO@TiO2 film that was constructed by controlling the wettability of the electrode surface is reported. The triphase photoelectrochemical system ensures an oxygen-rich interface microenvironment with constant and sufficiently high oxygen concentration. Moreover, the 3D porous micro-nano-hierarchical structures possess abundant active catalytic sites and a multidimensional electron transport pathway. The synergistic effect of the improved oxygen supply and the photoelectrode architecture greatly stabilizes and enhances the kinetics of the enzymatic reaction and H2O2 cathodic reaction, resulting in a 60-fold broader linear detection range and a higher accuracy compared with the conventional solid-liquid diphase system.

Photoelectrodes based on TiO2 decorated with Au nanoparticles (NPs) (Au-TiO2) have attracted great attention for visible-light-driven photoelectrochemical (PEC) water splitting applications. Herein, we report a highly efficient visible-light-responsive photoanode composed of Au NPs decorated well-separated TiO2 nanowire (NW) arrays with a length up to over 9 mu m. The photocurrent was found to be about 16 times higher than that of bare TiO2 NWs under visible-light illumination. Moreover, the photocurrent increased linearly with NW length, suggesting good charge dynamic properties and efficient utilization of the decorated Au NPs of the photoanode. These results indicate that the long and well-separated NW arrays have great potential for future development of PEC devices.

8-Arm star polypep(o)ides comprising cationic polylysine and hydrophilic polysarcosine blocks with a degree of polymerization (DP) of 30 per block are synthesized. Two different block sequences with polylysine as the inner and polysarcosine as the outer block and vice versa are obtained in addition to a statistical copolymer. Analysis of the enzymatic hydrolysis by the proteolytic enzyme trypsin demonstrates a strong dependence on structural arrangements. While polypept(o)ide disintegration is detectible after 24 h by Size Exclusion Chromatography (SEC), significant hydrolysis of the lysine blocks is only monitored after 48 h by fluorescamine labeling of the produced lysine and clearly accelerated in structures with more accessible polylysine blocks. All structures are capable of complexing plasmid DNA and form gene nanomedicines at sizes around or below 200 nm as determined by Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA), and Transition Electron Microscopy (TEM). The polyplex formation is slightly enhanced for both block structures over the random copolypept(o)ide. Moreover, it is demonstrated that the polyplexes can transport through mucus. The results highlight the importance of structural control in compartmentalized polymeric gene vector candidates with hydrophilic domains for potential mucosal delivery.