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Cancer patients by immune checkpoint therapy have achieved long-term remission, with no recurrence of clinical symptoms of cancer for many years. Nevertheless, more than half of cancer patients are not responsive to this therapy due to immune exhaustion. Here, we report a novel gene engineered exosome which is rationally designed by engineering PD1 gene and simultaneously enveloping an immune adjuvant imiquimod (PD1-Imi Exo) for boosting response of cancer immune checkpoint blockage therapy. The results showed that PD1-Imi Exo had a vesicular round shape (approximately 139 nm), revealed a significant targeting and a strong binding effect with both cancer cell and dendritic cell, and demonstrated a remarkable therapeutic efficacy in the melanoma-bearing mice and in the breast cancer-bearing mice. The mechanism was associated with two facts that PD1-Imi Exo blocked the binding of CD8+ T cell with cancer cell, displaying a PD1/PDL1 immune checkpoint blockage effect, and that imiquimod released from PD1-Imi Exo promoted the maturation of immature dendritic cell, exhibiting a reversing effect on the immune exhaustion through activating and restoring function of CD8+ T cell. In conclusion, the gene engineered exosome could be used for reversing T cell exhaustion in cancer immunotherapy. This study also offers a promising new strategy for enhancing PD1/PDL1 therapeutic efficacy, preventing tumor recurrence or metastasis after surgery by rebuilding the patients' immunity, thus consolidating the overall prognosis.

Infections with multidrug-resistant (MDR) Gram-negative bacteria, such as MDR Escherichia coli (E. coli), remain a challenge due to the lack of safe antibiotics and high fatality rates under anti-infection therapies. This work presents a form of biomimetic intelligent catalysis inspired by the selective biocatalytic property of macrophages (MΦs), consisting of an intelligent controlling center (a living MΦ) and a Fenton reaction catalyst (Fe3O4@poly(lactic-co-glycolic acid) (PLGA) nanoparticles) for killing MDR E. coli without harming normal cells. The MΦ–Fe3O4@PLGA particles (i.e., the intelligent catalysis particles) exhibit selective biocatalysis activity toward MDR E. coli by producing H2O2 and lipid droplets (LDs). This process activates the lipid metabolism and glycan biosynthesis and metabolism pathways based on the result of RNA sequencing data analysis. The H2O2 further reacts with Fe3O4@PLGA to form highly toxic hydroxyl radicals (·OH), while the LDs contain antimicrobial peptides and can target MDR E. coli. The highly toxic ·OH and antimicrobial peptides are shown to combat with MDR E. coli, such that the antibacterial efficiency of the MΦ–Fe3O4@PLGA particles against MDR E. coli is 99.29% ± 0.31% in vitro. More importantly, after several passages, the intelligent catalysis function of the MΦ–Fe3O4@PLGA particles is well maintained. Hence, the concept of biomimetic intelligent catalysts displays potential for treating diseases other than infections.

FeCoNi-based high-entropy alloys (HEAAs) attracted much attention because of their good thermodynamic stability, mechanical properties and soft magnetic properties. In this paper, Fe22Co22Ni22B34-xMnx (x = 6–22 at%) HEAAs were designed and the effects of Mn on the crystallization behaviors, magnetic performance, and mechanical property were investigated. The crystallization behaviors of the FeCoNiBMn HEAAs are: 1) 12–16 at% Mn: am → am’ + M23B6 → M23B6 + fcc; 2) 18 at% Mn: am → am’ + bcc + M23B6 → bcc + M23B6 → fcc + M23B6; and 3) 20–22 at% Mn: am → am’ + bcc → bcc + M23B6 → fcc + M23B6. Two parameters ΩA and VEC are proposed to predict the primary precipitates of FeCoNi-based HEAAs. All as-spun ribbons exhibit excellent soft magnetic properties with a very low coercivity (Hc) of less than 1.5 A/m and a maximum saturation magnetization (Bs) of 0.82 T. The 14 at% Mn alloy exhibits very low Hc of less than 4 A/m even after complete crystallization. Magnetic properties and Vickers hardness of crystalline ribbons are closely related to crystallization behaviors.

The deformation behavior of nanoporous metal (NPM) is important for their wide range of applications. Strain hardening can effectively enhance the resistance to the deformation. Here we report a novel nanoporous CrFe alloy with ordered structure, which is fabricated by selective phase dissolution of the two-phase Al–Ni–Fe–Cr high entropy alloy. The formation mechanism, microstructure and deformation behavior are investigated in details. The ordered nanoporous CrFe alloy behaves rapid strain hardening and high resistance to deformation. The regular skeletons can be entirely compacted between parallel two sides, which facilitates the densification of nanoporous alloy. Lots of internal boundaries are generated and act as barriers for the dislocation motion. This would favor of the improvement of strain hardening.

Infections caused by bacteria threaten human health, so how to effectively kill bacteria is an urgent problem. We therefore synthesized a NH2-MIL-125-GO-Pt ternary composite heterojunction with graphene oxide (GO) and platinum (Pt) nanoparticles co-doped with metal-organic framework (NH2-MIL-125) for use in photocatalytic and photothermal synergistic disinfection under white light irradiation. Due to the good conductivity of GO and the Schottky junction between Pt and MOF, the doping of GO and Pt will effectively separate and transfer the photogenerated electron-hole pairs generated by NH2-MIL-125, thereby effectively improving the photocatalytic efficiency of NH2-MIL-125. Meanwhile, NH2-MIL-125-GO-Pt has good photothermal effect under white light irradiation. Therefore, the NH2-MIL-125-GO-Pt composite can be used for effective sterilization. The antibacterial efficiency of NH2-MIL-125-GO-Pt against Staphylococcus aureus and Escherichia coli were as high as 99.94% and 99.12%, respectively, within 20 min of white light irradiation. In vivo experiments showed that NH2-MIL-125-GO-Pt could effectively kill bacteria and promote wound healing. This work brings new insights into the use of NH2-MIL-125-based photocatalyst materials for rapid disinfection of environments with pathogenic microorganisms.

Hydrogen production through water splitting is a promising path to develop renewable green energy. Effective, stable, and low-cost catalysts are the key to water splitting. In the present work, a series of self-supporting nanoporous alloys are prepared by using a dealloying process followed by electrooxidation. Among them, the np-AlFeNiO-4s sample exhibits remarkable activity (10 mA cm−2 at 32 mV for the HER and 278 mV for the OER) and good long-term stability (100 h) in alkaline conditions for both the HER and the OER. It only requires 1.56 V to reach 10 mA cm−2 current density for total water splitting performance. The very short time of electrooxidation can significantly improve the HER performance. Electrooxidation makes the metal and metal oxide sites on the electrode surface effectively coupled, which greatly enhances the kinetic rate of the Volmer and Heyrovsky steps. Appropriate electrooxidation is a rapid and easy way to improve the activity of the electrocatalyst, which has a broad application prospect in electrochemical water splitting.

Open wounds are prone to infection and difficult to heal, which even threatens the life of patients because bacterial infections can induce other lethal complications without prompt treatment. The commonly used antibiotics treatment for bacterial infections has been reported to cause globally bacterial resistance and even the occurrence of superbacteria. The highly effective and antibiotic-independent therapeutic strategies are urgently needed for treating various kinds of bacteria-infected diseases. In this work, we synthesized an eco-friendly nanohybrid material (ZnDMZ) consisting of a kind of biodegradable metal organic framework (MOF, ZIF-8) combined with Zn-doped MoS2 (Zn–MoS2) nanosheets, which exhibited great ability to kill bacteria and promote the healing of bacteria-infected wounds under 660 nm light irradiation. The underlying mechanism is that besides the local hyperthermia, the nanohybrid material exhibits enhanced photocatalytic performance than single component in it, i.e., it can also be excited by 660 nm light to produce more oxygen radical species (ROS) due to the following factors. On one hand, the Zn doping can reduce the work function and the band gap of MoS2, which promotes the movement of photoexcited electrons to the surface of the material. On the other hand, the combination between Zn–MoS2 and MOF induces the formation of a built-in electric field due to their work function difference, thus accelerating the separation of photoexcited electron-hole pairs. Because of the synergy of photocatalytic effect, photothermal effect and the released Zn ions, the synthesized ZnDMZ possessed a highly effective antibacterial efficacy of 99.9% against Staphylococcus aureus under 660 nm light irradiation for 20 min without cytotoxicity. In vivo tests showed that this nanohybrid material promoted the wound healing due to the released Zn ions. This nanohybrid will be promising for rapid and portable treatment of bacteria-infected open wounds in pathogenic bacteria contaminated environments.

Gram-negative bacteria are more resistant to antibacterial agents due to the outer membrane. Here, the authors use microwave irradiation to generate nanopores in the outer membrane allowing Garcinia nanoparticles to penetrate and damage the inner membrane leading to leakage and cell death.

β-lactamase, a kind of hydrolase in multi-drug resistant pathogens, can hydrolyze β-lactam antibiotics and make these kinds of antibiotics invalid. Small-molecular inhibitors about the enzyme and their mechanism are widely investigated but they may result in unavoidable adverse reactions and drug-resistance. Herein, we propose a new therapeutic strategy of Chinese materioherbology, in which herbal medicine or traditional Chinese medicinal herbs can be employed as biological functional materials or refreshed/excited by means of materialogy. Natural tea nanoclusters (TNCs) were extracted from tea to inhibit β-lactamase. Different from the mechanism of small-molecular inhibitors inhibiting enzymes by binding to the corresponding active sites, the TNCs as a cap cover the protein pocket and create a spatial barrier between the active sites and antibiotics, which was named “capping-pocket” effect. TNCs were combined with amoxicillin sodium (Amo) to treat the methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in mice. This combinatorial therapy remarkably outperforms antibiotic monotherapy in reducing MRSA infections and the associated inflammation in mice. The therapeutic strategy exhibited excellent biosafety, without any side effects, even in piglets. Hence, TNCs have great clinical value in potentiating β-lactam antibiotic activity for combatting multi-drug resistant pathogen infections and the ''pocket capping'' effect can guide the design of new enzyme inhibitors in near future.

Bone implants with antibacterial and osteogenic properties are important for clinical applications, but creating both properties simultaneously remains challenging. Here, the authors demonstrate a self-activating implant using a hydroxyapatite and molybdenum disulfide coating which accelerates bone regeneration and at the same time prevents bacterial infection.

Both phototherapy via photocatalysts and physical puncture by artificial nanostructures are promising substitutes for antibiotics when treating drug-resistant bacterial infectious diseases. However, the photodynamic therapeutic efficacy of photocatalysts is seriously restricted by the rapid recombination of photogenerated electron–hole pairs. Meanwhile, the nanostructures of physical puncture are limited to two-dimensional (2D) platforms, and they cannot be fully used yet. Thus, this research developed a synergistic system of Ag3PO4 nanoparticles (NPs), decorated with black urchin-like defective TiO2 (BU–TiO2-X/Ag3PO4). These NPs had a decreased bandgap compared to BU-TiO2-X, and BU-TiO2-X/Ag3PO4 (3:1) exhibited the lowest bandgap and the highest separation efficiency for photogenerated electron–hole pairs. After combination with BU-TiO2-X, the photostability of Ag3PO4 improved because the oxygen vacancy of BU-TiO2-X retards the reduction of Ag+ in Ag3PO4 into Ag0, thus reducing its toxicity. In addition, the nanospikes on the surface of BU-TiO2-X can, from all directions, physically puncture bacterial cells, thus assisting the hybrid's photodynamic therapeutic effects, alongside the small amount of Ag+ released from Ag3PO4. This achieves synergy, endowing the hybrid with high antibacterial efficacy of 99.76 ± 0.15% and 99.85 ± 0.09% against Escherichia coli and Staphylococcus aureus, respectively, after light irradiation for 20 min followed by darkness for 12 h. It is anticipated that these findings may bring new insight for developing synergistic treatment strategies against bacterial infectious diseases or pathogenic bacterial polluted environments.

Currently, platelet-rich plasma (PRP) is an attractive additive for bone repair materials. PRP could enhance the osteoconductive and osteoinductive of bone cement, as well as modulate the degradation rate of calcium sulfate hemihydrate (CSH). The focus of this study was to investigate the effect of different PRP ratios (P1: 20 vol%, P2: 40 vol%, and P3: 60 vol%) on the chemical properties and biological activity of bone cement. The injectability and compressive strength of the experimental group were significantly higher than those of the control. On the other hand, the addition of PRP decreased the crystal size of CSH and prolonged the degradation time. More importantly, the cell proliferation of L929 and MC3T3-E1 cells was promoted. Furthermore, qRT-PCR, alizarin red staining, and western blot analyses showed that the expressions of osteocalcin (OCN) and Runt-related transcription factor 2 (Runx2) genes and β-catenin protein were up-regulated, and mineralization of extracellular matrix was enhanced. Overall, this study provided insight into how to improve the biological activity of bone cement through PRP incorporation.

MXenes have emerged as potential antimicrobial materials. Here, the authors report on the creation of a Schottky junction to increase the charge separation between MXenes and semiconductor to increase photodynamic creation of reactive oxygen species under near infrared irradiation for antibacterial purposes.

A PLGA/Ti3C2 hybrid coating was successfully deposited on the surface of magnesium-strontium (Mg-Sr) alloys. Compared with the corrosion current density (icorr) of the Mg-Sr alloy (7.13 × 10−5 A/cm2), the modified samples (Mg/PLGA/Ti3C2) was lower by approximately four orders of magnitude (7.65 × 10−9 A/cm2). After near infrared 808 nm laser irradiation, the icorr of the modified samples increased to 3.48 × 10−7 A/cm2. The mechanism is that the local hyperthermia induced the free volume expansion of PLGA, and the increase in intermolecular gap enhanced the penetration of electrolytes. Meanwhile, the cytotoxicity study showed that the hybrid coating endowed the Mg-Sr alloy with enhanced biocompatibility.

Deep tissue infections can be difficult to treat due to limited light penetration associated with phototherapies. Here, the authors report on a bacterial capture system for antibiotic delivery and microwave-assisted killing of MRSA in osteomyelitis and demonstrate application in vivo.

Bacterial infection and related diseases are threatening the health of human beings. Photocatalytic disinfection as a simple and low-cost disinfection strategy is attracting more and more attention. In this work, TiO2 nanoparticles (NPs) were modified by co-doping of Ce and Er using the sol–gel method, which endowed TiO2 NPs with enhanced visible light photocatalytic performance but not pure ultraviolet photocatalytic properties compared the untreated TiO2. Our results disclosed that as the doping content of Er increased, the photocatalytic activity of modified TiO2 NPs initially increased and subsequently decreased. The same trend occurred for Ce doping. When the doping dose of Er and Ce is 0.5 mol% and 0.2 mol%, the 0.5Ce0.2Ti–O calcined at 800 °C presented the best antibacterial properties, with the antibacterial efficiency of 91.23% and 92.8% for Staphylococcus aureus and Escherichia coli, respectively. The existence of Er ions is thought to successfully turn the near-infrared radiation into visible region, which is easier to be absorbed by TiO2 NPs. Meanwhile, the addition of Ce ions can effectively extend spectral response range and inhibit the recombination of electrons and holes, enhancing the photocatalytic disinfection activity of co-doped TiO2.

Here, the authors apply transition metal doping in combination with phototermal therapy to treat Staphylococcus aureus-infected wounds, and show that release of ions by local heat enhances bacteria clearance and promotes tissue repair in a rat model of MRSA-infected wounds

Designing efficient photocatalysts for water splitting hydrogen evolution with low cost is a hot topic. In the present work, a α-Fe2O3/g-C3N4 photocatalyst with core-shell structure is successfully synthesized by an modified thermal etching method. Due to the synergy of Z-scheme and electron tunneling, the α-Fe2O3/g-C3N4 photocatalyst exhibits efficient water splitting propertiy under visible light, even red-light irradiation (about 700 nm). In-situ generated α-Fe2O3 nanoparticles facilitate the formation of 2D g-C3N4. The prepared α-Fe2O3/g-C3N4 photocatalyst shows an efficient photocatalytic activity between 500 nm and 700 nm due to the electron tunneling effect. The highest hydrogen evolution rate of α-Fe2O3/g-C3N4 photolyst is 5 mmol g−1 h−1 at λ > 420 nm. The present research provides the guidance for designing red-light-responsive photocatalysts for solar applications

Abstract A light‐inspired hydroxyapatite (Hap)/nitrogen‐doped carbon dots (NCDs) modified graphene oxide (GO) heterojunction film is developed, which shows a promoted separation of interfacial electrons and holes and an inhibited recombination efficiency via hole depletion. The metabolism of bacteria on this film is significantly inhibited under light irradiation, due to the enhanced photocatalytic and photothermal effects. In addition, the electron transfer from the plasmonic membrane to the GO/NCD/Hap film further inhibits the adenosine triphosphate process of bacteria, thus leading to the synergetic antibacterial efficacy. Meanwhile, the electron transfer between film and cell membrane induces the Ca2+ flow after irradiation, which can promote the migration and proliferation of cells and alkaline phosphatase enhancement, thus favoring the tissue reconstruction. An in vivo test discloses that the vascular injury repair is achieved through the Ca2+‐activated PLCγ1/ERK pathway, identified by the enhanced CD31 expression. Moreover, the increased CD4+/CD8+ lymphocytes are ameliorative by activating the PI3K/P‐AKT pathway. Consequently, the electron transfer boosts the synergic photodynamic and photothermal therapeutic effects for bacterial infection by Ca2+ flow for immunotherapy. This mild phototherapy approach with GO/NCDs/Hap, which can simultaneously repair injured vessels and relieve inflammation reactions, will increase the clinical application of noninvasive phototherapy in the near future.

In the present work, nanoporous Ag (np Ag) ribbons are prepared by chemical etching Cu60-xAg40Lax (x = 0, 3, 6 at.%) precursor alloys. The effects of precursor crystal structure on the morphology and mechanical properties of nanoporous Ag (np Ag) ribbons are investigated. The addition of La element inhibits the nucleation and growth of the crystal phases, then controls the phase compositions of the Cu-Ag-(La) precursors. The corroded np Ag with various ligament connectivity and homogeneity exhibits the different mechanical properties. Current study provides a general strategy for strengthening the np Ag metals by increasing the ligament connectivity and uniformity of the nanoporous metals.

Abstract Global multidrug‐resistant (MDR) bacteria are spreading rapidly and causing a great threat to human health due to the abuse of antibiotics. Determining how to resensitize MDR bacteria to conventional inefficient antibiotics is of extreme urgency. Here, a low‐temperature photothermal treatment (PTT, 45 °C) is utilized with red phosphorus nanoparticles to resensitize methicillin‐resistant Staphylococcus aureus (MRSA) to conventional aminoglycoside antibiotics. The antibacterial mechanism is studied by the proteomic technique and molecular dynamics (MD) simulation, which proves that the aminoglycoside antibiotics against MRSA can be selectively potentiated by low‐temperature PTT. The catalytic activity of 2‐aminoglycoside phosphotransferase (APH (2″))—a modifying enzyme—is demonstrated to be obviously inhibited via detecting the consumption of adenosine triphosphate (ATP) in the catalytic reaction. It is also found that the active site of aspartic acid (ASP) residues in APH (2″) is thermally unstable from the results of molecular dynamics simulation. Its catalytic ability is inhibited by preventing the deprotonating procedure for the target OH of gentamycin. The combined therapy also exhibits great biocompatibility and successfully treats MRSA infections in vivo. This low‐temperature PTT strategy has the potential to be an exogenous‐modifying enzyme inhibitor for the treatment of MDR bacterial infection.

Carbon-nanohorns have a unique morphology and structure yet little is known about the biocompatibility. Here, the authors investigate the biocompatibility and bio-interaction of carbon nanohorns, compare them to carbon nanotubes and show the superior biocompatibility and safety of the nanohorns.

With the aging of the population, the risk of osteoporotic vertebral compression fractures (OVCF) caused by osteoporosis increases rapidly. Surgeons often fill the bone defect with injectable polymethylmethacrylate (PMMA) bone cement through vertebroplasty. However, compared with cancellous bone, the higher mechanical properties of PMMA bone cement can easily lead to the fracture of the adjacent cone. Besides, the wound infection caused by surgery is also a serious problem. In order to solve these problems, we designed a new type of PMMA bone cement, by adding gelatin as a pore former, 5% (w/w) gentamicin sulfate (GS) for antibacterial purpose, and 30% (w/w) barium sulfate (BaSO _4 ) to provide excellent radiopacity. Compared with the traditional PMMA bone cement, with the dissolution of gelatin after being immersed in phosphate buffered saline (PBS) for 14 d, the mechanical properties of modified PMMA bone cement decreased by approximately 67%, which is close to the human cancellous bone. Besides, the release of GS increased 3.8 times, and the GS concentration remained above the minimum inhibitory concentration (MIC) for 12 d. In addition, the setting properties, contact angle, antibacterial ability, and cell compatibility of PMMA bone cement also maintained well. The integration and dissolution of gelatin were observed by a scanning electron microscope (SEM). All results indicate that the new type of gelatin-modified PMMA bone cement is a potential candidate material for vertebroplasty.

Abstract Biofilms have been related to the persistence of infections on medical implants, and these cannot be eradicated because of the resistance of biofilm structures. Therefore, a biocompatible phototherapeutic system is developed composed of MoS2, IR780 photosensitizer, and arginine–glycine–aspartic acid–cysteine (RGDC) to safely eradicate biofilms on titanium implants within 20 min. The magnetron‐sputtered MoS2 film possesses excellent photothermal properties, and IR780 can produce reactive oxygen species (ROS) with the irradiation of near‐infrared (NIR, λ = 700–1100 nm) light. Consequently, the combination of photothermal therapy (PTT) and photodynamic therapy (PDT), assisted by glutathione oxidation accelerated by NIR light, can provide synergistic and rapid killing of bacteria, i.e., 98.99 ± 0.42% eradication ratio against a Staphylococcus aureus biofilm in vivo within 20 min, which is much greater than that of PTT or PDT alone. With the assistance of ROS, the permeability of damaged bacterial membranes increases, and the damaged bacterial membranes become more sensitive to heat, thus accelerating the leakage of proteins from the bacteria. In addition, RGDC can provide excellent biosafety and osteoconductivity, which is confirmed by in vivo animal experiments.

The excellent photocatalysis is quite important for coating materials on implants, which can be photoinspired to kill bacteria by locally producing the reactive oxygen species (ROS) within a very short time. Herein, we developed a novel photocatalytic system of Au nanoparticles and carbon quantum dots loaded TiO2 nanotube array (TNTs/Au/CDs) on the surface of titanium. This system can exhibit enhanced near-infrared (NIR) light photocatalysis and photothermy because CDs can convert NIR light into the light of 500–600 nm and transfer electrons, which can inspire nano Au-catalyzed TNTs to generate ROS and enhance the surface plasmon resonance (SPR) effect of Au nanoparticles to produce more local photothermy. The enhanced photocatalysis and local photothermy can exhibit a synergistic effect to kill the bacteria highly effectively within a very short time by damaging the membranes of the bacteria. The antibacterial efficiency of the modified surface is 96.19% and 99.89% against Staphylococcus aureus and Escherichia coli, respectively, under 808 nm NIR light irradiation for 15 min. Keywords: NIR photocatalysis, Antibacterial, Au nanoparticles, Upconversion, Carbon quantum dots

Nanosized hydroxyapatite (HA) is a promising candidate for a substitute for apatite in bone in biomedical applications. Furthermore, due to its excellent bone bioactivity, nanosized strontium-substituted HA (SrHA) has aroused intensive interest. However, the size effects of these nanoparticles on cellular bioactivity should be considered. In this study, nanosized HA and SrHA with different dimensions and crystallization were synthesized by hydrothermal methods. The phase, crystallization and chemical composition were analyzed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR), respectively. The morphology was observed under field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The degradation behaviors of the samples were monitored by determining the ions release profile with inductively coupled plasma mass spectrometry (ICP-MS). The releasing behavior of Ca2+ and Sr2+ showed that the degradation rate was proportional to the specific surface area and inversely proportional to crystallization. The in vitro experiment evaluated by MG63 cells showed that SrHA nanorods with a length greater than 100 nm had the best biological performance both in cell proliferation and differentiation (* p < 0.05 compared with HA-1 and SrHA-1; * p < 0.01 compared with HA-2). In addition, HA nanoparticles with a lower aspect ratio had better bioactivity than higher ones (* p < 0.05). This study demonstrated that nanosized HA and SrHA with subtle differences (including dimensions, crystallization, specific surface area, and degradation rate) could affect the cellular growth and thus might have an impact on bone growth in vivo. This work provides a view of the role of nano-HAs as ideal biocompatible materials in future clinical applications.