Activation of the PPARγ/NF-κB pathway by A-MPDA@Fe3O4@PVP via scavenging reactive oxygen species to alleviate hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury (IRI) is a common pathological process during hepatectomy and liver transplantation and the two primary reasons for hepatic IRI are reactive oxygen species (ROS)-mediated oxidative stress and excessive inflammatory responses. Herein, a novel antioxidant nanodrug (A-MPDA@Fe3O4@PVP) is prepared by employing L-arginine-doped mesoporous polydopamine (A-MPDA) nanoparticles as the carrier for deposition of ultra-small ferric oxide (Fe3O4) nanoparticles and further surface modification with polyvinylpyrrolidone (PVP). A-MPDA@Fe3O4@PVP not only effectively reduces the aggregation of ultra-small Fe3O4, but also simultaneously replicates the catalytic activity of catalase (CAT) and superoxide dismutase (SOD). A-MPDA@Fe3O4@PVP with good antioxidant activity can rapidly remove various toxic reactive oxygen species (ROS) and effectively regulate macrophage polarization in vitro. In the treatment of hepatic IRI, A-MPDA@Fe3O4@PVP effectively alleviates ROS-induced oxidative stress, reduces the expression of inflammatory factors, and prevents apoptosis of hepatocytes through immune regulation. A-MPDA@Fe3O4@PVP can further protect liver tissue by activating the PPARγ/NF-κB pathway. This multiplex antioxidant enzyme therapy can provide new references for the treatment of IRI in organ transplantation and other ROS-related injuries such as fibrosis, cirrhosis, and bacterial and hepatic viral infection.

Oxygen Isotope Fractionation between Carbonate Minerals and Carbonic Acid Systems and Constraints for Environmental Science and Geological Processes.

The equilibrium oxygen isotope fractionation factor is widely used in geological thermometry. However, under most natural conditions, the oxygen isotope exchange is rare to reach equilibrium. Especially for the complex water-rock interaction process, the contribution of the H2CO3 solution, CO32- solution, Ca(HCO3)2 solution, and CaCO3 solution to the equilibrium oxygen isotope fractionation factor of this process is poorly understood. In view of this predicament, these key parameters are obtained by ab initio calculations. The results showed that the contributions of different carbonate minerals and different aqueous solutions to the equilibrium oxygen isotope fractionation factor were different. Among all nine carbonate minerals (dolomite, calcite, aragonite, magnesite, siderite, otavite, smithsonite, ankerite, and strontianite), the minerals with the highest and lowest reduced partition function ratios (RPFR) were siderite and strontianite, respectively. At the same time, the RPFR of nitratine, which has the same structure as carbonate, was studied. The RPFRs of the three most widely distributed carbonates in nature (dolomite, calcite, and aragonite) were dolomite > calcite > aragonite. Among the H2CO3 solution, CO32- solution, Ca(HCO3)2 solution, and CaCO3 solution, the H2CO3 solution had the strongest ability to enrich 18O. In addition, the equilibrium oxygen isotope fractionation factors between aqueous solutions and gas phase species (CO2(g), H2O(g), and O2(g), etc.) were calculated systematically. The results showed that the oxygen isotope fractionation factors between solutions and gas phases were often inconsistent with the temperature change direction and that the kinetic effects played a key role. These theoretical parameters obtained in this study will provide key equilibrium oxygen isotope constraints for water-rock interaction processes.

Amplified and Specific Staining of Protein Dimerization on Cell Membrane Catalyzed by Responsively Installed DNA Nanomachines for Cancer Diagnosis.

In situ staining of protein dimerization on cell membrane has an important significance in accurate diagnosis during perioperative period, yet facile integration of specific recognition function and local signal conversion/amplification abilities on membrane surface remains a great challenge. Herein, a two-stage catalytic strategy is developed by installing DNA nanomachines and employing. Specifically, dual-aptamer-assisted DNA scaffold perform a "bispecific recognition-then-computing" operation and the output signal initiate a membrane-anchored biocatalysis for self-assembly of DNA catalytic converters, that is, G-quadruplex nanowire/hemin DNAzyme. Then, localized-deposition of chromogenic polydopamine is chemically catalyzed by horseradish peroxidase-mimicking DNAzyme and guided by supramolecular interactions between conjugate rigid plane of G-tetrad and polydopamine oligomer. The catalytic products exhibit nanofiber morphology with a diameter of 80-120 nm and a length of 1-10 µm, and one-to-one localize on DNA scaffold for amplified and specific staining of protein dimers. The bispecific staining leads to a higher (≈3.4-fold) signal intensity than traditional immunohistochemistry, which is beneficial for direct visualization. Moreover, an efficient discrimination ability of the bispecific staining strategy is observed in co-culture model staining. This study provides a novel catalytic method for controlling deposition of chromogens and paves a new avenue to sensitively stain of protein-protein interactions in disease diagnosis.

Constraint Coupling of Redox Cascade and Electron Transfer Synchronization on Electrode-Nanosensor Interface for Repeatable Detection of Tumor Biomarkers.

Quantitative analysis of up-regulated biomarkers in pathological tissues is helpful to tumor surgery yet the loss of biomarker extraction and time-consuming operation limited the accurate and quick judgement in preoperative or intraoperative diagnosis. Herein, an immobilization-free electrochemical sensing platform is developed by constraint coupling of electron transfer cascade on electrode-nanosensor interface. Specifically, electrochemical indicator (Ri)-labeled single-stranded DNA on electroactive nanodonor (polydopamine, PDA) can be responsively detached by formation of DNA complex through the recognition and binding with targets. By applying the oxidation potential of Ri, nanosensor collisions on electrode surface trigger a cascade redox cycling of PDA and Ri through synchronous electron transfer, which boost the amplification of current signal output. The developed nanosensor exhibit excellent linear response toward up-regulated biomarkers (miRNA-21, ATP, and VEGF) with low detection limits (32 fM, 386 pM, and 2.8 pM). Moreover, background influence from physiological interferent is greatly reduced by restricted electron transfer coupling on electrode. The practical applicability is illustrated in sensitive and highly repeatable profiling of miRNA-21 in lysate of tumor cells and tumor tissue, beneficial for more reliable diagnosis. This electrochemical platform by employing electron transfer cascades at heterogeneous interfaces offers a route to anti-interference detection of biomarkers in tumor tissues.

Catalytically proficient ceria nanodots supported on redox-active mesoporous hosts for treatment of inflammatory bowel disease via efficient ROS scavenging.

Ceria nanozyme-based ROS scavengers have shown great potential in the treatment of inflammatory bowel disease (IBD) through microenvironment regulation. However, the currently developed nanotherapeutics suffer from difficulties in concomitantly achieving small sizes and stable interparticle dispersion which is pivotal to sufficient oxygen vacancies facilitating electron transfer and oxygen storage in the dynamic cycling of Ce3+/Ce4+ redox pairs. Herein, a hybrid nanosystem consisting of ceria nanodots supported on redox-active mesoporous hosts was developed to address the challenge of ROS scavenging, in particular the efficient downregulation of the readily renewable, highly concentrated H2O2 species. Specifically, Ce4+ ions oxidized from Ce3+ in weakly basic solution were captured and reduced in time by the abundant catechols on the mesoporous polydopamine nanoparticles. This led to strong restriction of ceria growth (∼2.8 nm) in the ion precipitation process and efficient maintenance of the Ce3+/Ce4+ ratio at a high value of 1.59 which is 4.8 fold higher than that of homogeneously nucleated ceria nanoparticles. Through this design, the nanohybrid showed an attractive catalytic performance in scavenging multiple ROS species, particularly the fast and recyclable conversion of H2O2. Thereby, significant suppression of the inflammatory cytokine/chemokine secretion was achieved by inhibiting the activation of NF-κB signaling pathways (5.1 fold higher as compared to those of pristine ceria nanoparticles), upregulating the Nrf2 signaling pathway, and reducing the proportion of M1 macrophages at IBD sites. Therapeutic efficiency was also demonstrated by the effective repair of the intestinal mucosal barrier by recovering the tight junction integrity in vivo. This study sheds light on the employment of redox-active hosts to support ceria catalysts for advancing anti-inflammation applications by boosting ROS scavenging performance.

Raman Spectroscopic Analysis of the Reaction between Al-Si Coatings and Steel.

Hot-stamped ultrahigh strength steel components are pivotal to automotive light-weighting. Steel blanks, often coated with an aluminum-silicon (Al-Si) layer to protect them from oxidation and decarburization, are austenitized within a furnace and then simultaneously quenched and formed into shape. The Al-Si coating melts within the furnace and reacts with iron from the steel to yield an intermetallic phase that provides some long-term corrosion protection. During the intermediate liquid phase, some of the coating may transfer to the furnace components, leading to maintenance costs and operational downtime. A detailed understanding of the coating transformation mechanism is needed to avoid such production issues while ensuring that final intermetallic coatings conform to specifications. We introduce cross-sectional Raman microscopic mapping as a method to rapidly elucidate the coating transformation mechanism. Raman spectroscopic fingerprints for relevant intermetallic compounds were determined using synthesized Al-Fe-Si ternary and Al-Fe binary compounds. These fingerprints were used to map the spatial distribution of intermetallic compounds through cross sections of Al-Si-coated 22MnB5 specimens that were heated at temperatures between 570 and 900 °C. These chemical maps show that the intermetallic fraction of the coating does not grow significantly until formation of η (Al5Fe2) at the steel interface, suggesting that η facilitates extraction of iron from the steel and subsequent diffusion through the coating. Under the heating conditions used here, a series of reactions ultimately lead to a silicon-rich τ2 (Al3FeSi) phase on top of the binary η phase. The technique presented here simplifies structural analysis of intermetallic compounds, which will facilitate prototyping of strategies to optimize hot stamping.

A mesoporous polydopamine-derived nanomedicine for targeted and synergistic treatment of inflammatory bowel disease by pH-Responsive drug release and ROS scavenging.

Repurposing clinically approved drugs to construct novel nanomedicines is currently a very attractive therapeutic approach. Selective enrichment of anti-inflammatory drugs and reactive oxygen species (ROS) scavenging at the region of inflammation by stimuli-responsive oral nanomedicine is an effective strategy for the treatment of inflammatory bowel disease (IBD). This study reports a novel nanomedicine, which is based on the excellent drug loading and free radical scavenging ability of mesoporous polydopamine nanoparticles (MPDA NPs). By initiating polyacrylic acid（PAA）polymerization on its surface, a "core-shell" structure nano-carrier with pH response is constructed. Then, under alkaline conditions, using the π-π stacking and hydrophobic interaction between the anti-inflammatory drug sulfasalazine (SAP) and MPDA, the nanomedicines (PAA@MPDA-SAP NPs) loaded efficiently (928 µ g mg-1) of SAP was successfully formed. Our results reveal that PAA@MPDA-SAP NPs can pass through the upper digestive tract smoothly and finally accumulate in the inflamed colon. Through the synergistic effect of anti-inflammation and antioxidation, it can effectively reduce the expression of pro-inflammatory factors and enhance the intestinal mucosal barrier, and finally significantly alleviate the symptoms of colitis in mice. Furthermore, we confirmed that PAA@MPDA-SAP NPs have good biocompatibility and anti-inflammatory repair ability under inflammation induction through human colonic organoids. In summary, this work provides a theoretical basis for the development of nanomedicines for IBD therapy.

First-principles calculations of equilibrium Ga isotope fractionations between several important Ga-bearing minerals and aqueous solutions.

This study predicts the equilibrium isotope fractionation factors for some important Ga-bearing species, including major minerals, aqueous solutions and gas phase systems. Equilibrium isotope fractionations of Ga were investigated by using the first-principles quantum chemistry method at the B3LYP/6-311+G(d) level. The 103ln(RPFR) values of orthoclase, albite, quartz, kaolinite, forsterite, montmorillonite, gibbsite, cassiterite, aragonite, sphalerite and calcite were calculated with the volume variable cluster model. The 103ln(RPFR)s of these minerals decrease in the following order: orthoclase > albite > quartz > kaolinite > forsterite > montmorillonite > gibbsite > cassiterite > aragonite > sphalerite > calcite. The solvation effect of Ga3+-bearing aqueous species is modeled by the water-droplet method, and the 103ln(RPFR)s of Ga3+-bearing aqueous species decrease in the following order: [Ga(OH)4]- > [Ga(OH)3] > [Ga(OH)]2+ > [Ga(OH)2]+ > [Ga(H2O)6]3+. The calculation results show that equilibrium isotope fractionations of Ga between different minerals, solutions and gas phases are appreciable. Among minerals, Ga isotope fractionation exhibits the largest value between orthoclase and calcite. Ga isotopic fractionation factor between these two minerals can reach 3.18 per mil at 100 °C. Ga isotope fractionations between Ga-bearing aqueous species and minerals are important for obtaining information about the different geochemical processes, such as surficial geochemistry. This study has provided important Ga isotope fractionation factors.

Flower-like Nanozyme with Highly Porous Carbon Matrix Induces Robust Oxidative Storm against Drug-Resistant Cancer.

Reactive oxygen species (ROS) generators are sparking breakthroughs in sensitization and treatment of therapy-resistant tumors, yet the efficacy is drastically compromised by limited substrate concentrations, short lifetimes of free radicals, and restricted oxidative damage. Herein, a flower-like nanozyme with highly permeable leaflets accommodating catalytic metal sites was developed to address the challenges by boosting substrate and product accessibility. In the formation of a zeolite imidazole framework, cobalt ions promoted catalytic polymerization and deposition of polydopamine. The polymers acted as a stiffener for preventing framework collapse and maneuvering pore reopening during carbonization. The cobalt single-atom/cluster sites in the highly porous matrix generated peroxidase/oxidase-like activities with high catalytic efficiency (Kcat/Km) up to 6 orders of magnitude greater than that of conventional nano-/biozymes. Thereby, a robust ROS storm induced by selective catalysis led to rapid accumulation of oxidative damage and failure of antioxidant and antiapoptotic defense synchronization in drug-resistant cancer cells. By synergy of a redox homeostasis disrupter co-delivered, a significantly high antitumor efficiency was realized in vivo. This work offers a route to kinetically favorable ROS generators for advancing the treatment of therapy-resistant tumors.

Dual factor coactivatable fluorescent nanosensor with boosted cytoplasmic biomarker accessibility toward selective tumor imaging.

Fluorescent nanosensor-based tumor imaging holds great promise in cancer diagnosis and treatment assistance, yet the signal contrast is heavily hampered by the unspecific/unwanted activation at microscopic regions with a highly restricted local abundance of biomarkers. Herein, we developed an activation boosting strategy by the integration and manipulation of dual-factor coactivation of sensing and lysosome escape facilitated the rise of cytosolic biomarker accessibility. By employing hybrid DNA probes on gold nanoquenchers, ATP sensing initiated conformation switch of the corresponding aptamer units triggered the exposure of a hidden toehold in a loop structure. Sequentially, miRNA-21 sensing was triggered by toehold-mediated strand displacement and detachment of the binding complexes. The application of lysosomotropic agent chloroquine at optimized time interval facilitated the release of nanosensors into the cytosol and a ∼10.5-fold increment of intracellular fluorescence in vitro, while coactivation improved the cancer-to-normal cell signal ratio by ∼5.9 times. The synergy effects led to a high tumor-to-normal tissue ratio value of ∼7.9 in the in vivo imaging results. This strategy establishes a new paradigm of fluorescent nanosensors for selective and specific tumor imaging.

Combination wound healing using polymer entangled porous nanoadhesive hybrids with robust ROS scavenging and angiogenesis properties.

Nanoadhesives can achieve tight wound closure by connecting biomacromolecules from both sides. However, previously developed adhesive systems suffered from suboptimal wound healing efficiency due to the lack of interparticle cohesion, sufficient reactive oxygen species (ROS)-scavenging sites, and angiogenesis consideration. Herein, we developed a polymer entangled porous nanoadhesive system to address the above challenge by synergy of three functional components. Firstly, hybrid mesoporous silica nanoparticles with highly integrated polydopamine (MS-PDA) were prepared by templated synthesis. The entangling between PVA polymer and MS-PDA contributed to much stronger cohesion between nanoparticles, which led to 75% larger adhesion strength. As confirmed by in vitro and in vivo evaluations, the highly exposed catechol groups boosted the scavenging activity of ROS (1.8-4.1 fold enhancement as compared with nonporous counterpart). Consequently, more macrophages exhibited anti-inflammatory phenotype, leading to 2-2.6 fold lower pro-inflammatory cytokine levels. Moreover, the sustained release of bioactive SiO44- by the disintegration of nanoparticles contributed to ∼3-fold higher expression of VEGF and enhanced new blood vessel formation, as well as better wound repair. This platform can provide a new paradigm for developing multifunctional nanoadhesive systems in treating skin wounds. STATEMENT OF SIGNIFICANCE: PVA polymer entangled mesoporous nanoadhesives of polydopamine (PDA)/silica hybrids with the combination of excellent wound closure effect, boosted ROS-scavenging activity, and significant angiogenesis ability were developed for improving the suboptimal skin wound healing efficiency. This strategy not only greatly advances our ability to rationally integrate repairing elements in nanoadhesives for manipulating combined processes of interfacial events during wound healing, but also offers general implications toward application of polymers to reinforce the adhesion strength in nanoadhesive systems. In addition, our findings on the impacts of pore effects mediated ROS species conversion and polymer entanglement may also trigger great interests and facilitate the development/broad application of therapeutic adhesives.

Melanin Nanoparticle-Actuated Redox-State Perturbation and Temporally Photoactivated Thermal Stress for Synergistic Tumor Therapy.

The elevation of antioxidant defense systems by adaptation response to localized reactive oxygen species (ROS) accumulation may confer resistance to excessive oxidative stress and cause therapeutic lethality. Herein, a highly effective tumor therapy is developed through perturbation in cellular redox homeostasis. Specifically, metal-ion-assisted oxidation polymerization of the melanin precursor (l-DOPA) whose carboxyl groups exert a charge-shielding effect leads to the formation of catechol-rich but quinone-deficient nanoparticles (NPs). These NPs possess appreciable ROS-scavenging ability, and particularly the raised quinone group levels in oxidized products can then trigger subsequent depletion of antioxidative species (GSH) and, in turn, the redox-cycle consumption of catechol/quinone groups. After incubating with cells, varying degrees of redox-state and energy metabolism fluctuations with time (∼6 h) are observed, where ROS/GSH levels rebound to a maximum peak (up to ∼280%) higher than the normal redox state after hitting the bottom within a short time (1 h). Notably, systematically triggered redox stress response can sensitize cells to an extremely endangered metastable state. The synergy of temporally photoactivated thermal stress can produce overwhelming oxidative stress, thus leading to significant inhibition of cancer cells. This work established a new paradigm of redox perturbator-based programed and combined cancer therapy.

Polydopamine/SiO2 Hybrid Structured Superamphiphobic Fabrics with Good Photothermal Behavior.

In recent years, photothermal materials that can convert light into heat energy have attracted extensive attention. In this work, we report a simple and effective approach to construct a self-cleaning photothermal superamphiphobic fabric. Dopamine (DA) can self-polymerize into polydopamine (PDA) and adhere to the surface of cotton fabric as a secondary reaction platform. Then, SiO2 nanoparticles were in situ grown on the PDA@fabric surface by the sol-gel method. The PDA clusters can not only provide good photothermal conversion performance but also be integrated with SiO2 to create micro-nano rough structures. Finally, the surface of SiO2 was modified by the long chain of fluorosilane to decrease the fabric surface energy, resulting in superamphiphobicity. The contact angles of water, ethylene glycol, and pump oil on the modified fabric surface could reach 161.1, 158.1, and 142.2°, respectively, making the fabric resistant to contamination by water, common beverages, and oil. Due to the adhesion of the PDA layer, the strong binding force between the fabric and SiO2 particles enabled the modified fabric to withstand various chemical and mechanical attacks, showing excellent mechanical robustness and harsh environmental stability. More importantly, the surface temperature of the modified fabric could be increased from 19.6 to 37.0 °C, which is close to the human body temperature, under the irradiation of simulated sunlight (I = 15 A, 300 s). The photothermal superamphiphobic fabrics with self-cleaning properties show great promise in the photothermal conversion field.

Polycatechol-Derived Mesoporous Polydopamine Nanoparticles for Combined ROS Scavenging and Gene Interference Therapy in Inflammatory Bowel Disease.

Benefiting from the evolution of nanotechnology, the combination therapy by gene interference and reactive oxygen species (ROS) scavenging are expected, which holds great potential in inflammatory bowel disease (IBD) therapy. However, the functional integration of different therapeutic modules through interface modification of gene vectors for safe and efficient treatment is urgently needed. Herein, we present a catechol chemistry-mediated core-shell nanoplatform for ROS scavenging-mediated oxidative stress alleviation and siRNA-mediated gene interference in a dextran sulfate sodium (DSS)-induced colitis model. The nanoplatform is constructed by employing mesoporous polydopamine nanoparticles (MPDA NPs) with surface modification of amines as the porous core for TNF-α-siRNA loading (31 wt %) and exerts an antioxidant function, while PDA-induced biomineralization of the calcium phosphate (CaP) coating is used as the pH-sensitive protective shell to prevent siRNA from premature release. The CaP layer degraded under weakly acidic subcellular conditions (lysosomes); thus, the synergistic integration of catechol and cation moieties on the exposed surface of MPDA resulted in an efficient lysosomal escape. Subsequently, effective ROS scavenging caused by the electron-donating ability of MPDA and efficient knocking down (40.5%) of tumor necrosis factor-α (TNF-α) via sufficient cytosolic gene delivery resulted in a synergistic anti-inflammation therapeutic effect both in vitro and in vivo. This work establishes the first paradigm of synergistic therapy in IBD by ROS scavenging and gene interference.

Interfacially responsive electron transfer and matter conversion by polydopamine-mediated nanoplatforms for advancing disease theranostics.

Polydopamine (PDA) is an artificial melanin polymer that has been spotlighted due to its extraordinary optoelectronic characteristics and advance theranosctic applications in biomaterial fields. Moreover, interactions on the nano-bio interface interplay whereby substances exchange in response to endogenous or exogenous stimuli, and electron transfer driven by light, energy-level transitions, or electric field greatly affect the functional performance of PDA-modified nanoparticles. The full utilization of potential in PDA's interfacial activities, optoelectrical properties and related responsiveness is therefore an attractive means to construct advanced nanostructures for regulating biological processes and metabolic pathways. Herein, we strive to summarize recent advances in the construction of functional PDA-based nanomaterials with state-of-the-art architectures prepared for modulation of photoelectric sensing and redox reversibility, as well as manipulation of photo-activated therapeutics. Meanwhile, contributions of interfacial electron transfer and matter conversion are highlighted by discussing the structure-property-function relationships and the biological effects in their featured applications including disease theranostics, antibacterial activities, tissue repair, and combined therapy. Finally, the current challenges and future perspectives in this emerging research field will also be outlined. Recent advances on polydopamine-based nanotherapeutics with an emphasis on their interfacial activities, optoelectrical properties and related responsiveness are reviewed for providing insightful guidance to the rational design of integrated theranostic nanoplatforms with high performance in the biomedical fields. This article is categorized under: Diagnostic Tools > Diagnostic Nanodevices Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Photothermally triggered melting and perfusion: responsive colloidosomes for cytosolic delivery of membrane-impermeable drugs in tumor therapy.

A cell membrane barrier which dominates the therapeutic efficacy and systemic side effects is a major bottleneck in the field of drug delivery. Herein, a therapeutic system capable of photothermally triggered on-demand and cytosolic delivery was achieved by polydopamine (PDA) nanoparticle-stabilized colloidosomes. An organic phase change material (PCM, saturated fatty acids) was employed as the lipid core for Pickering emulsification and drug encapsulation, and arginine was utilized as a linker to induce the directional interactions between nanoemulsion droplets and heterogeneously nucleated PDA nanoparticles. Moreover, the PDA particle stabilizers concomitantly mediated the grafting of hydrophilic polymer PEG to further improve dispersibility. The resultant colloidosomes after cooling possess lowered melting points and superior dispersion stability over 7 days. When irradiated with near-infrared light (808 nm), sequential processes of fatty acid melting and direct drug perfusion into the cytosol took place within 10 min. The employment of vorinostat (SAHA, histone deacetylase inhibitor) as a model membrane-impermeable drug resulted in remarkable enhancement of anti-cancer effects both in vitro (5.2 fold reduction in IC50) and in vivo (7.3 fold increase in tumor inhibition rate) with respect to the free drug. The remotely triggered transformable nanoplatform paves a new avenue of responsive and efficient cytosolic perfusion to overcome biological membrane barriers on the basis of colloidosomes.

A Bioinspired Hemostatic Powder Derived from the Skin Secretion of Andrias davidianus for Rapid Hemostasis and Intraoral Wound Healing.

High-performance hemostasis has become increasingly essential in treating various traumas. However, available topical hemostats still have various drawbacks and side-effects. Herein, hemostatic powders derived from the skin secretion of Andrias davidianus (SSAD) with controllable particle size are prepared using feasible frozen-ball milling following lyophilization for hemorrhage-control. Scanning electron microscopy, rheometry, and Brunauer-Emmett-Teller test are used to characterize the coagulation-promoting surface topography, rheological properties, and porous structure of the SSAD particles. The blood-coagulation assays showed that the SSAD powders can induce blood-absorption in a particle size-dependent manner. Particle sizes of the SSAD powders larger than 200 µm and smaller than 800 µm greatly affect the blood-clotting rate. Associated with the thromboelastography (TEG) and amino acid/protein composition analyses, the accessibility and diffusion of blood are mainly dependent on the wettability, adhesivity, and clotting factors of the SSAD particles. Rapid hemostasis in vivo further involves three hemorrhage models (liver, femoral artery, and tail) as well as an oral wound model, which suggest favorable hemostatic and simultaneous regenerative effects of the SSAD hemostatic powder. Considering its degradability and good biocompatibility, SSAD can be an optimal candidate for a new class of inexpensive, natural, and promising hemostatic and wound-dressing agent.

Redox Host-Guest Nanosensors Installed with DNA Gatekeepers for Immobilization-Free and Ratiometric Electrochemical Detection of miRNA.

Electrochemical nanosensors by integrating functional nucleic acids and nanomaterials hold a great promise in the fast detection of biomarkers, yet the current systems possess limitations on the accessibility of target-probe and probe-electrode interactions and the repeatability of detection. Herein, a host-guest assembly strategy is developed to build redox nanosensors for an immobilization-free and ratiometric electrochemical detection system. Specifically, electroactive molecule (Em ) guests are loaded in porous hosts of polydopamine nanoparticles (MPDA) to act as dual-signal redox reporters. Hybrid DNA probes of G-quadruplex and a single-stranded anchor DNA are installed as gatekeepers for sealing the mesopores. Thereby, miRNA triggered Em release by strand displacement reactions and the homogeneous transportation of the hosts/guests to the electrode facilitate the generation of reference signal/response signal at different potentials. Concomitantly applied NIR irradiation boosts the electron transfer from MPDA to the electrode and results in a tenfold increase in the reference signal. Finally, the sensing system through the differential pulse voltammetry method achieves a highly repeatable detection (relative standard deviation 3.8%) of miRNA with a lower detection limit (362 × 10-15 m). This attractive system paves the way for rational designs of advanced electrochemical biosensors and smart diagnosis.

Polydopamine Nanosheets Doped Injectable Hydrogel with Nitric Oxide Release and Photothermal Effects for Bacterial Ablation and Wound Healing.

The development of wound dressings with combined antibacterial activities and pro-healing functions has always been an intractable medical task for treating bacterial wound infection. Herein, a novel injectable hybrid hydrogel dressing is developed, which is doped with nitric oxide (NO) donor (N,N'-di-sec-butyl-N,N'-dinitroso-1,4-phenylenediamine, BNN6) loaded two-dimensional polydopamine nanosheets (PDA NS). The hydrogel matrix is in situ formed through dynamic Schiff base crosslinking between hydrazide-modified γ-polyglutamic acid (γ-PGA-ADH) and aldehyde-terminated Pluronic F127 (F127-CHO). Under 808 nm irradiation, the embedded PDA NS exhibits outstanding photothermal transform properties (56.1%) and on-demand NO release. The combination of photothermal and NO gas therapy with a synergistic antibacterial effect works on both Escherichia coli and Staphylococcus aureus in vitro. Furthermore, a full-thickness skin defect model also demonstrates that the hybrid hydrogel shows outstanding antibacterial properties and effectively accelerates the wound healing process. Overall, this study provides a facile and promising method for the fabrication of PDA NS based multifunctional hydrogel dressing for the application of infectious skin wound healing.

Interfacial Engineering of Hybrid Polydopamine/Polypyrrole Nanosheets with Narrow Band Gaps for Fluorescence Sensing of MicroRNA.

Nanoquencher-based biosensors have emerged as powerful tools for the detection of tumor markers, where challenges in efficiently docking the π-electron interaction interface toward nucleic acid probes containing π-electron-rich units of bases and fluorescent dyes still remain. Herein, we present hybrid polydopamine/polypyrrole nanosheets (PDA-PPy-NS) with π electron coupling and ultranarrow band gap (0.29 eV) by interfacial engineering of polymer hybrids at the nanoscale. PDA-PPy-NS were first prepared through oxidant-induced polymerization of pyrrole on PDA nanosheets. By utilizing fluorescent-dye-labeled single-stranded DNA as a probe, the hybrid nanoquencher showed ultrahigh fluorescence quenching ability, i.e., a Cy5-ssDNA/nanoquencher mass ratio of 36.9 under the complete quenching condition, which is comparable to that of graphene oxide. It was demonstrated that the energy level coupling of nanosheets and nucleic acid dye (Cy5) was the key factor contributing to the efficient photoinduced electron transfer (PET). Subsequently, the nanoquencher/DNA probe was proved to possess superior sensitivity and selectivity for efficient and reliable detection of miRNA-21 with a detection limit of 23.1 pM. Our work proves that the π-electron-rich biosensor interface can significantly enhance the PET efficiency, providing a theoretical basis for developing novel high-performance sensors.