Amino acid-based metallo-supramolecular nanoassemblies capable of regulating cellular redox homeostasis for tumoricidal chemo-/photo-/catalytic combination therapy.

Nanozymes, as nanomaterials with natural enzyme activities, have been widely applied to deliver various therapeutic agents to synergistically combat the progression of malignant tumors. However, currently common inorganic nanozyme-based drug delivery systems still face challenges such as suboptimal biosafety, inadequate stability, and inferior tumor selectivity. Herein, a super-stable amino acid-based metallo-supramolecular nanoassembly (FPIC NPs) with peroxidase (POD)- and glutathione oxidase (GSHOx)-like activities was fabricated via Pt4+-driven coordination co-assembly of l-cysteine derivatives, the chemotherapeutic drug curcumin (Cur), and the photosensitizer indocyanine green (ICG). The superior POD- and GSHOx-like activities could not only catalyze the decomposition of endogenous hydrogen peroxide into massive hydroxyl radicals, but also deplete the overproduced glutathione (GSH) in cancer cells to weaken intracellular antioxidant defenses. Meanwhile, FPIC NPs would undergo degradation in response to GSH to specifically release Cur, causing efficient mitochondrial damage. In addition, FPIC NPs intrinsically enable fluorescence/photoacoustic imaging to visualize tumor accumulation of encapsulated ICG in real time, thereby determining an appropriate treatment time point for tumoricidal photothermal (PTT)/photodynamic therapy (PDT). In vitro and in vivo findings demonstrated the quadruple orchestration of catalytic therapy, chemotherapeutics, PTT, and PDT offers conspicuous antineoplastic effects with minimal side reactions. This work may provide novel ideas for designing supramolecular nanoassemblies with multiple enzymatic activities and therapeutic functions, allowing for wider applications of nanozymes and nanoassemblies in biomedicine.

Bioinspired Conductive Enhanced Polyurethane Ionic Skin as Reliable Multifunctional Sensors.

Ionogels prepared from ionic liquid (IL) have the characteristics of nonevaporation and stable performance relative to traditional hydrogels. However, the conductivities of commonly used ionogels are at very low relative to traditional hydrogels because the large sizes of the cation and anion in an IL impedes ion migration in polymer networks. In this study, ultradurable ionogels with suitable mechanical properties and high conductivities are prepared by impregnating IL into a safe, environmentally friendly water-based polyurethane (WPU) network by mimicking the ion transport channels in the phospholipid bilayer of the cell membrane. The increase in electrical conductivity is attributed to the introduction of carboxylic acid in the hard segment of WPU; this phenomenon regularly arranges hard segment structural domains by hydrogen bonding, forming ionic conduction channels. The conductivities of their ionogels are >28-39 mS cm-1 . These ionogels have adjustable mechanical properties that make the Young's modulus value (0.1-0.6 MPa) similar to that of natural skin. The strain sensor has an ultrahigh sensitivity that ranges from 0.99 to 1.35, with a wide sensing range of 0.1%-200%. The findings are promising for various ionotronics requiring environmental stability and high conductivity characteristics.

Silk fibroin based wearable electrochemical sensors with biomimetic enzyme-like activity constructed for durable and on-site health monitoring.

Flexible biomimetic sensors have encountered a bottleneck of sensitivity and durability, as the sensors must directly work within complex body fluid with ultra-trace biomarkers. In this work, a wearable electrochemical sensor on a modified silk fibroin substrate is developed using gold nanoparticles hosted into N-doped porous carbonizated silk fibroin (AuNPs@CSF) as active materials. Taking advantage of the inherent biocompatibility and flexibility of CSF, and the high stability and enzyme-like catalytic activity of AuNPs, AuNPs@CSF-based sensor exhibits durable stability and superior sensitivity to monitor H2O2 released from cancer cell (4T1) and glucose in sweat. The detection limits for H2O2 and glucose are low to be 1.88 µM and 23 µM respectively, and the sensor can be applied in succession within 30 days at room temperature. Further, physical cross-linking of polyurethane (PU) with SF well matches with the skin tissue mechanically and provides a flexible, robust and stable electrode-tissue interface. AuNPs@CSF is applied successfully for wearable electrochemical monitoring of glucose in human sweat.The present AuNPs@CSF will possess a potential application in clinical diagnosing of H2O2- or glucose-related diseases in future.

A Matrix-Metalloproteinase-Responsive Hydrogel System for Modulating the Immune Microenvironment in Myocardial Infarction.

Injectable hydrogels carrying therapeutic factors to modulate the infarct immune microenvironment show great potential in the treatment of myocardial infarction (MI). However, conventional injectable hydrogels release therapeutic factors in an uncontrolled manner, which leads to poor treatment efficacy and acute side effects on normal tissues. In this work, a matrix metalloproteinase (MMP)2/9-responsive hydrogel system (MPGC4) is developed, considering the characteristics of the post-MI microenvironment. MPGC4 consists of tetra-poly(ethylene glycol) (PEG) hydrogels and a composite gene nanocarrier (CTL4) that is composed of carbon dots (CDots) coupled with interleukin-4 plasmid DNA via electrostatic interactions. MPGC4 can be automatically triggered to release CTL4 on demand after MI to regulate the infarct immune microenvironment. In addition, due to the photoluminescence properties of CDots, a large amount of viscoelastic MPGC4 is found to be retained in situ after injection into the infarct region without leakage. The in vitro results demonstrate that CTL4 promotes proinflammatory M1 macrophage polarization to the anti-inflammatory M2 subtype and contributes to cardiomyocyte survival through macrophage transition. In a rat model of MI, MPGC4 clears MMPs and precisely targets CTL4 to the infarcted region. In particular, MPGC4 improves cardiac function by modulating macrophage transition to reduce early inflammatory responses and proangiogenic activity.

2D Co3O4 modified by IrO2 nanozyme for convenient detection of aqueous Fe2+ and intercellular H2O2.

A portable sensor for visual monitoring of Fe2+ and H2O2, two-dimensional Co3O4 modified by nano-IrO2 (IrO2@2D Co3O4) was prepared in this work, for the first time, with the help of microwave radiation at 140 °C, which was further stabilized onto common test strips. The present IrO2@2D Co3O4 possessed superior dual-function enzyme-like activity with low toxicity and excellent biocompatibility. Especially, trace Fe2+ and H2O2 could exclusively alter their enzyme-like catalytic activity with discriminating hyperchromic or hypochromic effect, i.e., from blue to colorless or to dark blue for both IrO2@2D Co3O4 dispersion and its functionalized test strips. The linear regression equations were A652 = 0.5940 - 0.00041 cFe2+ (10-8 M, R2 = 0.9927) for Fe2+ and ∆A652 = 0.0023 cH2O2 + 0.00025 (10-7 M, R2 = 0.9982) for H2O2, respectively. When applied to visual monitoring of aqueous Fe2+ and intercellular H2O2, the recoveries were 101.2 ~ 102.5% and 95.8 ~ 103.7% with detection limits of 1.25 × 10-8 mol/L and 1.02 × 10-7 mol/L, respectively, far below the permitted values in drinking water set by the World Health Organization. The mechanisms for the enhancing enzyme-mimetic activity of IrO2@2D Co3O4 and its selective responses to Fe2+ and H2O2 were investigated in detail.

Autonomous Bionanorobots via a Cage-Shaped Silsesquioxane Vehicle for In Vivo Heavy Metal Detoxification.

Nanorobots hold great promise for integrated drug delivery systems that are responsive to molecular triggers. Herein, we successfully developed an automatic smart bionanorobot that has transport capability and recognizes and removes zinc ions from poisoned cells based on nanoscale polyhedral oligomeric silsesquioxane molecules. This intelligent bionanorobot can easily move inside and outside the cell and find zinc ions owing to its highly selective recognition to zinc ions and high cell permeability, especially the well-combined high penetration and strong binding energy. More importantly, it was also found that this intelligent bionanorobot can restore round HeLa cells to a normal fusiform cell morphology following high-concentration zinc treatment and does not interfere with cell proliferation and division. It was also shown by in vivo experiments that the bionanorobot can inhibit persistent enlargement of the liver caused by zinc ion poisoning.

Biomimetic synthesis of 2D ultra-small copper sulfide nanoflakes based on reconfiguration of the keratin secondary structure for cancer theranostics in the NIR-II region.

Two-dimensional transition metal dichalcogenides have attracted widespread attention in cancer theranostics due to their high specific surface area and excellent photothermal conversion properties. However, their dimensions and biodegradability have limited the exploration of the therapeutic properties of transition metal dichalcogenides. Herein, we explore the mechanism of the keratin α-helix-to-random coil transition, as an actuation mechanism for the controllable design and precise synthesis of two-dimension copper sulfide nanoflakes (CuS NFs) with high absorption in the NIR-II window. Upon mixing keratin and Cu2+, the hydrogen bonds that maintain the α-helix are broken by copper ions to form biuret coordination, while the structure of the α-helix is transformed into a random coil, providing a more scalable space for the growth of CuS NFs. The CuS NFs prepared in this way possess the great advantages of outstanding uniformity, size controllability, and biodegradability. Importantly, the CuS NFs in the NIR-II window show an excellent photothermal conversion efficiency (32.9%) and extraordinary photoacoustic signal. This work updates the fabrication of two-dimensional transition metal dichalcogenides and greatly enhances their competitiveness in the area of cancer theranostics in the NIR-II region, and provides significant theoretical and practical opportunities for the development of keratin using biomimetic synthesis.

Phycocyanin - carbon dots nanoprobe for the ratiometric fluorescence determination of peroxynitrite.

As a kind of reactive oxygen species, peroxynitrite is related to various diseases closely such as cancer and neurodegenerative diseases. Constructing probes with highly specific ability and a wide linear detection range for peroxynitrite detection is crucial for understanding the pathogenesis of related diseases and optimizing treatments. In this work, we developed a novel luminescent ratiometric fluorescence nanoprobe (PC-CDs) based on carbon dots and phycocyanin. PC-CDs are constructed by amidation reaction between carbon dots and phycocyanin. The nanoprobe we obtained has a good ability of distinguishing peroxynitrite from other reactive oxygen species and interfering substances. Moreover, the linear range of the nanoprobe is 0.5-100 µM and the limit of detection is 0.5 µM when detecting peroxynitrite. In the spiked recovery experiments under phosphate buffered saline (PBS) environment, our nanoprobe has a good recovery performance and the recovery is 99% - 104%, which will be beneficial to the further development of peroxynitrite testing and the research progress of related diseases. Finally, we discuss the quenching mechanism of peroxynitrite for nanoprobe, and found that there is the combination of dynamic and static quenching in the quenching process.

Fast dopamine detection based on evanescent wave detection platform.

A compact evanescent wave detection platform (EWDP) is developed for the detection of fluorescence gold nanoclusters. The EWDP employs a simple optical system and a Si-based photodetector SOP-1000 assembly to improve the optical efficiency and detection sensitivity. A microfluidic sample cell is also used to decrease the amount of analyte to 200 µL (The volume of sample cell is really about 30 µL). On this basis, we design a strategy for detecting dopamine (DA) based on the photoinduced electron transfer (PET) quenching mechanism. By introduction of tyrosinase (TYR) during the detection, the testing time is shortened to 1 min. The fluorescence emission signal decreased dramatically and the quenching ratio (F0-F)/F0 is linearly related to the concentration of DA in the range of 0.03-60 µM with a detection limit of 0.03 µM. Additionally, this detection platform has potential applications for DA fast detection in the microsamples.

Polydopamine-Induced Multilevel Engineering of Regenerated Silk Fibroin Fiber for Photothermal Conversion.

Solid photothermal materials with favorable biocompatibility and modifiable mechanical properties demonstrate obvious superiority and growing demand. In this work, polydopamine (PDA) induced functionalization of regenerated silk fibroin (RSF) fibers has satisfactory photothermal conversion ability and flexibility. Based on multilevel engineering, RSF solution containing PDA nanoparticles is wet spun to PDA-incorporating RSF (PDA@RSF) fibers, and then the fibers are coated with PDA via oxidative self-polymerization of dopamine to form PDA@RSF-PDA (PRP) fibers. During the wet spinning process, PDA is to adjust the mechanical properties of RSF by affecting its hierarchical structure. Meanwhile, coated PDA gives the PRP fibers extensive absorption of near-infrared light and sunlight, which is further fabricated into PRP fibrous membranes. The temperature of PRP fibrous membranes can be adjusted and increases to about 50 °C within 360 s under 808 nm laser irradiation with a power density of 0.6 W cm-2 , and PRP fibrous membranes exhibit effective photothermal cytotoxicity both in vitro and in vivo. Under the simulated sunlight, the temperature of PRP fiber increases to more than 200 °C from room temperature and the material can generate 4.5 V voltage when assembled with a differential thermal battery, which means that the material also has the potential for flexible wearable electronic devices.

Reinforcement of Silk Microneedle Patches for Accurate Transdermal Delivery.

Microneedles (MNs) have attracted considerable attention in the pharmaceutical field as a minimally invasive delivery alternative to hypodermic needles. Current material systems of MNs have gradually shifted from metals, ceramics, and silicon to polymer in consideration of toughness and drug loading capacity. Silk fibroin (SF) is considered one of the most promising alternatives because it combines the ability to maintain the activity of biomolecules, adjustable mechanical strength, and excellent biocompatibility. However, the strength and hardness of SF MNs need to be carefully optimized to ensure skin epidermis penetration and controlled drug release, which are rarely explored in reported works. Here, the synergistic effect of glutaraldehyde-based cross-linking and water vapor annealing post-treatment is presented as an effective method to promote the formation of SF molecular networks and the mechanical strength of SF MNs. Moreover, the reinforced MN substrate is coated with a drug-loaded SF layer with low crystallinity. The drug release experiments demonstrate the successful controlled release of rhodamine B, horseradish peroxidase, and tetracycline, which suggests the great potential in the application of vaccine, antibiosis, cosmetology, and so forth.

Biomimetic Salinity Power Generation Based on Silk Fibroin Ion-Exchange Membranes.

Powering implanted medical devices (IMDs) is a long-term challenge since their use in biological environments requires a long-term and stable supply of power and a biocompatible and biodegradable battery system. Here, silk fibroin-based ion-exchange membranes are developed using bionics principles for reverse electrodialysis devices (REDs). Silk fibroin nanofibril (SNF) membranes are negatively and positively modified, resulting in strong cation and anion selectivity that regulates ion diffusion to generate electric power. These oppositely charged SNF membranes are assembled with Ag/AgCl electrodes into a multicompartment RED. By filling them with 10 and 0.001 mM NaCl solutions, a maximum output power density of 0.59 mW/m2 at an external loading resistance of 66 kΩ is obtained. In addition, 10 pairs of SNF membranes produce a considerable voltage of 1.58 V. This work is a proof of concept that key components of battery systems can be fabricated with protein materials. Combined with the emergence of water-based battery technologies, the findings in this study provide insights for the construction of tissue-integrated batteries for the next generation of IMDs.

Subcutaneous Energy/Signal Transmission Based on Silk Fibroin Up-Conversion Photonic Amplification.

Transmission of energy and signals through human skin is critically important for implantable devices. Because near-infrared (NIR) light can easily penetrate through human skin/tissue, in this study we report on silk fibroin (SF) up-conversion photonic amplifiers (SFUCPAs) integrated into optoelectronic devices, which provide a practical approach for subcutaneous charging and communication via NIR lasers. SFUCPAs achieve a 4 times higher fluorescence than the control, which gives rise to a 47.3 time increase in subcutaneous NIR energy conversion efficiency of a single fibrous dye-sensitized solar cell compared with the control. Moreover, the hybrid printed electrodes exhibited reversible switching to NIR exposure with a response time of ∼1.06/1.63 s for a 3 s ON/OFF switch. Owing to the flexible, biocompatible, and cost-efficient design NIR-driven optoelectronic performance, the SFUCPAs are promising for use in applications of subcutaneous medical electronics for charging, storing information, and controlling implanted devices.

Tailoring NiCoAl layered double hydroxide nanosheets for assembly of high-performance asymmetric supercapacitors.

NiCoAl layered double hydroxide nanosheets (NiCoAl-LDHNs) were prepared by a one-step solvothermal method. The shape and size of the obtained nanosheets are optimized by adjusting the solvothermal time and the molar concentration ratio of Ni2+/Co2+ to obtain the electrode material with the best performance. When the solvothermal time is 9 h and the molar concentration ratio of Ni2+/Co2+ is 1:1, NiCoAl-LDHNs has the best morphology and electrochemical performance. When assembled into a supercapacitor, NiCoAl-LDHN-9 has a high specific capacitance of 1228.5 F g-1 at 1 A g-1. As the current density is increased to 20 A g-1, the specific capacitance is 1001.8 F g-1, which still has a high capacitance retention of 81.6%. When NiCoAl-LDHN-9 was assembled into an asymmetric supercapacitor, NiCoAl-LDHN-9//AC has a specific capacitance of 102.1 F g-1 at 0.5 A g-1. The asymmetric supercapacitor devices also show excellent electrochemical performance in terms of energy density (35.9 Wh kg-1 at 225.8 W kg-1), power density (4.8 kW kg-1 at 22.2 Wh kg-1) and cycle life (capacitance retention rate after 10,000 cycles is 87.1%). Those results indicate that NiCoAl-LDHN have the potential to be promising electrode materials for high performance supercapacitors.

A TiS2/Celgard separator as an efficient polysulfide shuttling inhibitor for high-performance lithium-sulfur batteries.

The rapid capacity loss caused by the shuttling effect of polysulfides is one of the great challenges of Li-S batteries. In this work, we adopted a simple solid-phase sintering method to synthesize titanium disulfide (TiS2) and further demonstrated it as a superior modifier of separators for Li-S batteries. Two commonly adopted modification processes of separators, including vacuum filtration (VF) and slurry casting (SC) have been used to prepare TiS2/Celgard separators. TiS2-VF/Celgard can better restrain the polysulfide shuttling effect compared with TiS2-SC/Celgard. A TiS2-VF/Celgard-based Li-S battery has a reversible capacity of 771.6 mA h g-1, with a capacity retention of 645.6 mA h g-1 after 500 cycles at 2.0 C, corresponding to a capacity fading rate of ∼0.033% per cycle. This study has shown the potential of TiS2 as a multifunctional modifier of separators for high performance and long cycle life Li-S batteries.

From Molecular Reconstruction of Mesoscopic Functional Conductive Silk Fibrous Materials to Remote Respiration Monitoring.

Turning insulating silk fibroin materials into conductive ones turns out to be the essential step toward achieving active silk flexible electronics. This work aims to acquire electrically conductive biocompatible fibers of regenerated Bombyx mori silk fibroin (SF) materials based on carbon nanotubes (CNTs) templated nucleation reconstruction of silk fibroin networks. The electronical conductivity of the reconstructed mesoscopic functional fibers can be tuned by the density of the incorporated CNTs. It follows that the hybrid fibers experience an abrupt increase in conductivity when exceeding the percolation threshold of CNTs >35 wt%, which leads to the highest conductivity of 638.9 S m-1 among organic-carbon-based hybrid fibers, and 8 times higher than the best available materials of the similar types. In addition, the silk-CNT mesoscopic hybrid materials achieve some new functionalities, i.e., humidity-responsive conductivity, which is attributed to the coupling of the humidity inducing cyclic contraction of SFs and the conductivity of CNTs. The silk-CNT materials, as a type of biocompatible electronic functional fibrous material for pressure and electric response humidity sensing, are further fabricated into a smart facial mask to implement respiration condition monitoring for remote diagnosis and medication.

Interplay between Light and Functionalized Silk Fibroin and Applications.

Silkworm silk has been considered to be a luxurious textile for more than five thousand years. Native silk fibroin (SF) films have excellent (ca. 90%) optical transparency and exhibit fluorescence under UV light. The silk dyeing process is very important and difficult, and methods such as pigmentary coloration and structural coloration have been tested for coloring silk fabrics. To functionalize silk that exhibits fluorescence, the in vivo and in vitro assembly of functional compounds with SF and the resulting amplification of fluorescence emission are examined. Finally, we discuss the applications of SF materials in basic optical elements, light energy conversion devices, photochemical reactions, sensing, and imaging. This review is expected to provide insight into the interaction between light and silk and to inspire researchers to develop silk materials with a consideration of history, material properties, and future prospects.

Tailoring the Meso-Structure of Gold Nanoparticles in Keratin-Based Activated Carbon Toward High-Performance Flexible Sensor.

Flexible biosensors with high accuracy and reliable operation in detecting pH and uric acid levels in body fluids are fabricated using well-engineered metal-doped porous carbon as electrode material. The gold nanoparticles@N-doped carbon in situ are prepared using wool keratin as both a novel carbon precursor and a stabilizer. The conducting electrode material is fabricated at 500 °C under customized parameters, which mimics A-B type (two different repeating units) polymeric material and displays excellent deprotonation performance (pH sensitivity). The obtained pH sensor exhibits high pH sensitivity of 57 mV/pH unit and insignificant relative standard deviation of 0.088%. Conversely, the composite carbon material with sp2 structure prepared at 700 °C is doped with nitrogen and gold nanoparticles, which exhibits good conductivity and electrocatalytic activity for uric acid oxidation. The uric acid sensor has linear response over a range of 1-150 µM and a limit of detection 0.1 µM. These results will provide new avenues where biological material will be the best start, which can be useful to target contradictory applications through molecular engineering at mesoscale.

Primary and Secondary Mesoscopic Hybrid Materials of Au Nanoparticles@Silk Fibroin and Applications.

In this work, we demonstrate the principle of mesoscopic construction of silk fibroin (SF) hybrid materials, which endows the materials with new performance. In implementing this strategy, mediating molecules, wool keratin (WK) molecules, were adopted to in-line synthesize Au nanoparticles (WK@AuNPs), which further create the stable linkage of AuNPs with SF nanofibril networks via templated ß-crystallization. Fourier transform infrared spectroscopy, X-ray diffraction, and atomic force microscopy demonstrate that the mesoscopic hybrid network structure of the hybrid materials is different from neat SF materials, which gives rise to various new performances, that is, long-stable fluorescence emission. As the fluorescence emission can be characteristically annealed by Cu ions, therefore be adopted as the highly selective ion probes. Moreover, as WK@AuNPs are homogeneously connected to SF nanofibril networks, the carbonization of the materials leads to secondary hybrid materials of carbon-Au, where nano-sized Au particles are well distributed in carbonized mesoscopic conductive carbon networks. Such hybrid materials of carbon-Au can be further fabricated into electrochemical (i.e., dopamine) sensors, which are demonstrated to have excellent sensing performance.

Transient bioelectrical devices inspired by a silkworm moth breaking out of its cocoon.

Transient devices have attracted extensive interest because they allow changes in physical form and device function under the control of external stimuli or related commands and have very broad application prospects for information security, biomedical care and the environment. Transient bioelectrical devices were fabricated inspired by a silkworm moth breaking out of its cocoon, which has shown many advantages, including the use of mild stimulation, biocompatible materials, a simple process, and a universal strategy. For the fabrication of the transient devices, heat-sensitive microspheres with a 9.3 mol L-1 LiBr solution in wax shells were prepared by microfluidic technology, which were then assembled into silk fibroin (SF) electronic materials/devices, such as SF conductive film, an LED circuit on SF film, and a Ag/SF film/Pt/SF film memristor. The contribution from the LiBr/wax microspheres to the transient time of the SF films upon exposure to heat was quantitatively investigated. This approach was applied to transiently dissolve a flexible Ag-nanowire resistance circuit line on a SF substrate. Moreover, memristors constructed with a functional layer of SF were destroyed by melting the LiBr/wax microspheres. This technique paves the way for realizing transient bioelectrical devices inspired by biological behavior, which have been well optimized by nature via evolution.