Engineering of a Hollow-Structured Cu2−XS Nano-Homojunction Platform for Near Infrared-Triggered Infected Wound Healing and Cancer Therapy

Infection and malignant tumors are the most common diseases in people's daily life, which seriously threaten human health. Because of the frequent and extensive administration of antibiotics and chemodrugs, the prevalence of multidrug-resistant bacteria and tumor cells makes the conventional therapies less effective and even invalid. To overcome the repugnant dilemma, herein the authors devise and develop a hollow Cu_2−XS nano-homojunction (nano-HJ) platform for the effective eradication of both bacteria and tumors upon tissue-penetrable near-infrared (NIR) light irradiation. Hyaluronan (HA) is covalently decorated onto the nano-homojunctions (nano-HJs) surface to enhance their biocompatibility, tumor-targeting ability, and cutaneous wound healing capability. The decorated nano-HJs exert robust NIR-activatable bactericidal modality and accelerate the cutaneous regeneration of bacteria-invaded full-thickness wounds through the synergy of photothermal/photodynamic effects, glutathione depletion, and HA assistance. After loading anticancer drug doxorubicin in the cavity of nano-HJs, the antitumor therapy efficacy is greatly strengthened both in vitro and in vivo by the collaborative photo-chemotherapy. Accordingly, this work not only highlights the great promise of the Cu_2−XS nano-HJs in the treatment of bacteria-induced contagious diseases and malignant tumors but also opens up a new research direction for the biomedical application of homojunction nanoplatforms in the future.     

Quaternized Silicon Nanoparticles with Polarity‐Sensitive Fluorescence for Selectively Imaging and Killing Gram‐Positive Bacteria

With the emergence of antibiotic resistance, developing new antibiotics and therapies for combating bacterial infections is urgently needed. Herein, a series of quaternized fluorescent silicon nanoparticles (SiNPs) are facilely prepared by the covalent reaction between amine‐functionalized SiNPs and carboxyl‐containing N‐alkyl betaines. It is found that the bactericidal efficacy of these quaternized SiNPs increases with the length of the N‐alkyl chain, and SiNPs conjugated with N,N‐dimethyl‐N‐octadecylbetaine (BS‐18), abbreviated as SiNPs‐C₁₈, show the best antibacterial effect, whose minimum inhibitory concentrations for Gram‐positive bacteria are 1–2 μg mL^?1. In vivo tests further confirm that SiNPs‐C₁₈ have excellent antibacterial efficacy and greatly reduce bacterial load in the infectious sites. The SiNPs‐C₁₈ exhibit low cytotoxicity toward mammalian cells (including normal liver and lung cells, red blood cells, and macrophages), enabling them to be useful for clinical applications. Besides, the quaternized SiNPs exhibit polarity‐dependent fluorescence emission property and can selectively image Gram‐positive bacteria, thereby providing a simple method to successfully differentiate Gram‐positive and Gram‐negative bacteria. The present work represents the first example that successfully turns fluorescent SiNPs into metal‐free NP‐based antibiotics with simultaneous bacterial imaging and killing capability, which broadens the applications of fluorescent SiNPs and advances the development of novel antibacterial agents.     

Hollow Mesoporous Zirconia Nanocapsules for Drug Delivery

Hollow mesoporous zirconia nanocapsules (hm‐ZrO₂) with a hollow core/porous shell structure are demonstrated as effective vehicles for anti‐cancer drug delivery. While the highly porous feature of the shell allows the drug, doxorubicin(DOX), to easily pass through between the inner void space and surrounding environment of the particles, the void space in the core endows the nanocapsules with high drug loading capacity. The larger the inner hollow diameter, the higher their DOX loading capacity. A loading of 102% related to the weight of hm‐ZrO₂ is achieved by the nanocapsules with an inner diameter of 385 nm. Due to their pH‐dependent charge nature, hm‐ZrO₂ loaded DOX exhibit pH‐dependent drug releasing kinetics. A lower pH offers a faster DOX release rate from hm‐ZrO₂. Such a property makes the loaded DOX easily release from the nanocapsules when up‐taken by living cells. Although the flow cytometry reveals more uptake of hm‐ZrO₂ particles by normal cells, hm‐ZrO₂ loaded DOX release more drugs in cancer cells than in normal cells, leading to more cytotoxicity toward tumor cells and less cytotoxicity to healthy cells than free DOX.     

Bacterial Outer Membrane-Coated Mesoporous Silica Nanoparticles for Targeted Delivery of Antibiotic Rifampicin against Gram-Negative Bacterial Infection In Vivo

The efficacy of conventional antibiotics therapeutics has declined rapidly due to the emerged antibiotic resistance. There is an urgent need to develop novel approaches to address the problem of antibiotic shortage, particularly for Gram-negative bacteria. Herein, a biomimetic nanodelivery system is proposed to enhance the bacterial targeting and uptake of rifampicin (Rif), a traditional antibiotic but not effective against Gram-negative bacteria. The biomimetic nanodelivery system (Rif@MSN@OMV) is composed of outer membrane vesicles (OMVs) isolated from E. coli as shell and rifampicin-loaded mesoporous silica nanoparticles (MSNs) as core. The OMVs greatly improve the uptake of MSNs in E. coli, but not in Gram-positive bacteria S. aureus, owing to the homotypic targeting function of the OMVs. The Rif@MSN@OMV exhibits enhanced antimicrobial activity against E. coli and completely eradicates bacteria at an equivalent rifampicin concentration (4 µg mL⁻¹) while free rifampicin shows weak bactericidal activity. Meanwhile, the Rif@MSN@OMV maintains good biocompatibility both in vitro and in vivo. More importantly, the Rif@MSN@OMV elevates survival rate of infected mice and reduces bacterial load in intraperitoneal fluid and organs. Overall, the OMVs-coated nanodelivery system provides a novel strategy to improve the antimicrobial efficacy of conventional antibiotic or repurpose drugs for treatment of Gram-negative bacterial infections.     

Antimicrobial Gallium‐Doped Phosphate‐Based Glasses

Novel quaternary gallium‐doped phosphate‐based glasses (1, 3, and 5 mol % Ga₂O₃) were synthesized using a conventional melt quenching technique. The bactericidal activities of the glasses were tested against both Gram‐negative (Escherichia coli and Pseudomonas aeruginosa) and Gram‐positive (Staphylococcus aureus, methicillin‐resistant Staphylococcus aureus, and Clostridium difficile) bacteria. Results of the solubility and ion release studies showed that these glass systems are unique for controlled delivery of Ga³⁺. ⁷¹Ga NMR measurements showed that the gallium is mostly octahedrally coordinated by oxygen atoms, whilst FTIR spectroscopy provided evidence for the presence of a small proportion of tetrahedral gallium in the samples with the highest gallium content. FTIR and Raman spectra also afford an insight into the correlation between the structure and the observed dissolution behavior via an understanding of the atomic‐scale network bonding characteristics. The results confirmed that the net bactericidal effect was due to Ga³⁺, and a concentration as low as 1 mol % Ga₂O₃ was sufficient to mount a potent antibacterial effect. The dearth of new antibiotics in development makes Ga³⁺ a potentially promising new therapeutic agent for pathogenic bacteria including MRSA and C. difficile.     

Eradicating Multidrug‐Resistant Bacteria Rapidly Using a Multi Functional g‐C3N4@ Bi2S3 Nanorod Heterojunction with or without Antibiotics

Wound infections caused by multidrug‐resistant (MDR) bacteria are hard to treat because of tolerance to existing antibiotics, repeated infection, and concomitant inflammation. Herein, zinc atom–doped g‐C₃N₄ and Bi₂S₃ nanorod heterojunctions (CN–Zn/BiS) are investigated for disinfection under near‐infrared light (NIR). The photocatalysis of CN–Zn/BiS is enhanced because of efficient charge separation during the interface electron field and increased oxygen adsorption capacity. Then, 99.2% antibacterial efficiency is shown toward methicillin‐resistant Staphylococcus aureus (MRSA) and 99.6% toward Escherichia coli under 10 min NIR irradiation. Meanwhile, a strategy for the combination of lapsed β‐lactam antibiotics with the photosensitizer CN–Zn/BiS is provided to kill MRSA by NIR without observable resistance, suggesting an approach to solve the problem of bacterial infection with NIR light penetrability and for exploiting new anti‐infection methods. The CN–Zn/BiS nanocomposite can also regulate genes and the inflammatory response through inflammatory factors (IL‐1β, IL‐6, TNF‐α, and iNOS) in vivo to accelerate tissue regeneration and thereby promote wound healing.     

Polycationic Synergistic Antibacterial Agents with Multiple Functional Components for Efficient Anti‐Infective Therapy

Multifunctional antibacterial photodynamic therapy is a promising method to combat regular and multidrug‐resistant bacteria. In this work, eosin Y (EY)‐based antibacterial polycations (EY‐QEGED? R, R = ? CH₃ or ? C₆H₁₃) with versatile types of functional components including quaternary ammonium, photosensitizer, primary amine, and hydroxyl species are readily synthesized based on simple ring‐opening reactions. In the presence of light irradiation, such antibacterial polymers exhibit high antibacterial efficiency against both Escherichia coli and Staphylococcus aureus. In particular, EY‐QEGED? R elicits a remarkable synergistic antibacterial activity owing to the combined photodynamic and quaternary ammonium antibacterial effects. Due to its rich primary amine groups, EY‐QEGED? R also can be readily coated on different substrates, such as glass slides and nonwoven fabrics via an adhesive layer of polydopamine. The resultant surface coating of EY‐QEGED? CH₃ (s‐EY‐QEGED? CH₃) produces excellent in vitro antibacterial efficacy. The plentiful hydroxyl groups impart s‐EY‐QEGED? CH₃ with potential antifouling capability against dead bacteria. The antibacterial polymer coatings also demonstrate low cytotoxicity and good hemocompatibility. More importantly, s‐EY‐QEGED? CH₃ significantly enhances in vivo therapeutic effects on an infected rat model. The present work provides an efficient strategy for the rational design of high‐performance antibacterial materials to fight biomedical device‐associated infections.     

Rapid Sterilization and Accelerated Wound Healing Using Zn2+ and Graphene Oxide Modified g‐C3N4 under Dual Light Irradiation

Wound healing is affected by bacterial infection and related inflammation, cell proliferation and differentiation, and tissue remodeling. Current antibiotics therapy cannot promote wound healing and kill bacteria at the same time. Herein, hybrid nanosheets of g‐C₃N₄‐Zn²⁺@graphene oxide (SCN‐Zn²⁺@GO) are prepared by combining Zn²⁺ doped sheet‐like g‐C₃N₄ with graphene oxide via electrostatic bonding and π–π stacking interactions to assist wound healing and kill bacteria simultaneously by short‐time exposure to 660 and 808 nm light. The gene expressions of matrix metalloproteinase‐2, type I collagen, type III collagen, and interleukin β in fibroblasts are regulated by GO and released Zn²⁺, which can accelerate wound healing. Co‐irradiation produces an antibacterial ratio over 99.1% within a short time because of the synergistic effects of both photodynamic antibacterial and photothermal antibacterial treatments. The hyperthermia produced by 808 nm light illumination can weaken the bacterial activity. And these bacteria can be easily killed by membrane destruction, protein denaturation, and disruption of bacterial metabolic pathways due to reactive oxygen species produced under 660 nm light irradiation. This strategy of Zn²⁺ and GO modification can increase the antibacterial efficacy of SCN and accelerate wound healing at the same time, which makes this SCN‐Zn²⁺@GO be very promising in bacteria‐infected wound healing therapy.     

Reactive Oxygen Species–Activatable Liposomes Regulating Hypoxic Tumor Microenvironment for Synergistic Photo/Chemodynamic Therapies

Tumors have adapted various cellular antidotes and microenvironmental conditions to subsist against photodynamic therapy (PDT) and chemodynamic therapy (CDT). Here, the development of reactive oxygen species (ROS)‐activatable liposomes (RALP) for therapeutic enhancement by simultaneously addressing the critical questions in PDT and CDT is reported. The design of RALP@HOC@Fe₃O₄ features ROS‐cleavable linker molecules for improved tumor penetration/uptake and ondemand cargo releasing, and integration of Fe₃O₄ and an oxaliplatin prodrug for smart regulation of hypoxia tumor microenvironment. Glutathione stored by the tumor cells is consumed by the prodrug to produce highly toxic oxaliplatin. Depletion of glutathione not only avoids the undesired annihilation of ROS in PDT, but also modulates the chemical specie equilibria in tumors for H₂O₂ promotion, leading to greatly relieved tumor hypoxia and PDT enhancement. Synergistically, Fe (II) in the hybrid RALP formulation can be fuelled by H₂O₂ to generate ?OH in the Fenton reaction, thus elevating CDT efficiency. This work offers a strategy for harnessing smart, responsive, and biocompatible liposomes to enhance PDT and CDT by regulating tumor microenvironment, highlighting a potential clinical translation beneficial to patients with cancer.     

Novel Redox‐Responsive Polymeric Magnetosomes with Tunable Magnetic Resonance Property for In Vivo Drug Release Visualization and Dual‐Modal Cancer Therapy

Monitoring of in vivo drug release from nanotheranostics by noninvasive approaches remains very challenging. Herein, novel redox‐responsive polymeric magnetosomes (PolyMags) with tunable magnetic resonance imaging (MRI) properties are reported for in vivo drug release monitoring and effective dual‐modal cancer therapy. The encapsulation of doxorubicin (DOX) significantly decreases PolyMags' T₂‐contrast enhancement and transverse relaxation rate R₂, depending on the drug loading level. The T₂ enhancement and R₂ can be recovered once the drug is released upon PolyMags' disassembly. T₂‐ and T₂*‐MRI and diffusion‐weighted imaging (DWI) are utilized to quantitatively study the correlation between MRI signal changes and drug release, and discover the MR tuning mechanisms. The in vivo drug release pattern is visualized based on such tunable MRI capability via monitoring the changes in T₂‐weighted images, T₂ and T₂* maps, and R₂ and R₂* values. Interestingly, the PolyMags possess excellent photothermal effect, which can be further enhanced upon DOX loading. The PolyMags are highly efficacious to treat breast tumors on xenograft model with tumor‐targeted photothermal‐ and chemotherapy, achieving a complete cure rate of 66.7%. The concept reported here is generally applicable to other micellar and liposomal systems for image‐guided drug delivery and release applications toward precision cancer therapy.     

Multivalent Glycosheets for Double Light–Driven Therapy of Multidrug‐Resistant Bacteria on Wounds

With the evergrowing threat posed by multidrug resistance of bacteria, the development of effective antibacterial agents remains a global challenge. Infection with multidrug‐resistant bacteria in hospitals significantly impairs the healing of wounds caused by deep‐burn injuries or diabetic foot ulceration, leading to a high mortality rate among these patients. A multivalent glycosheet for the double light–driven therapy against multidrug‐resistant Pseudomonas aeruginosa (P. aeruginosa) infection on wounds is developed here. Galactose‐ and fucose‐based ligands are self‐assembled to form a glyco‐layer on the surface of thin‐layer molybdenum disulfide, producing the glycosheets capable of selectively localizing P. aeruginosa through multivalent carbohydrate–lectin interactions. The glycosheets loaded with antibiotics have proven applicable for: 1) near‐infrared‐light driven, in situ thermal release of antibiotics, increasing bacterial membrane permeability, and 2) white light–driven reactive‐oxygen‐species production to more thoroughly kill the bacteria. The targetability, together with the light sensibility, of the glycosheets enables a highly effective and optically controlled therapeutic regime for the healing of wounds infected by multidrug‐resistant as well as clinically isolated P. aeruginosa.     

Multi‐Caged IrOx for Facile Preparation of “Six‐in‐One” Nanoagent for Subcutaneous and Lymphatic Tumors Inhibition against Recurrence and Metastasis

Single nanocarriers with intrinsic characteristics of diagnosis, effective therapy against solid malignancies with fatal metastasis, and tumor microenvironment regulation are promising in construction of a simple and effective multimode nanotheranostic system. Herein, multi‐caged IrO_x nanocarriers are fabricated by direct thermal hydrolysis strategy, which exhibit good sono‐photodynamic response, outstanding gemstone spectral computed tomography, and photoacoustic (PA) imaging capabilities, universal loading, and pinpoint drug release properties. As a proof of concept, a gemstone spectral computed tomography/PA/fluorescence imaging–guided oxygen self‐sufficient sono‐photo‐chemotherapy nanoagent by simple loading of doxorubicin is constructed. The remarkable synergistic therapy and excellent hypoxia releasing capabilities can remove both subcutaneous and sentinel lymph nodes metastasis tumors, and effectively suppress tumor recurrence and lung metastasis, thus greatly prolonging survival time. The study provides an attractive candidate to construct a “six‐in‐one” (tri‐modal therapies and three imaging modalities) tumor theranostic system.     

Shining Light on Multidrug-Resistant Bacterial Infections: Rational Design of Multifunctional Organosilver-Based AIEgen Probes as Light-Activated Theranostics for Combating Biofilms and Liver Abscesses

The intricate environment of biofilms provides a heaven for bacteria to escape antibiotic eradication, leading to persistent chronic infections. Therefore, it is urgently needed to develop effective therapies to combat biofilm-associated infections. To address this problem, a series of antimicrobial agents are designed and synthesized utilizing triphenylamine imidazole silver complexes ( TPIMS ). Due to the photoactivated release of Ag⁺ coupled with aggregation-induced emission (AIE) properties and efficient ¹O₂ generation, TPIMS exhibits excellent visual diagnostic capabilities and potent broad-spectrum antimicrobial activity, showing antimicrobial efficacy against both Gram (+) and Gram (−) bacteria. Additionally, TPIMS shows extraordinary antibacterial performance and biofilm resistance against methicillin-resistant Staphylococcus aureus (MRSA), with reduced potential for resistance thanks to the synergistic effect of phototoxicity and dark toxicity. Notably, among the TPIMS variants tested, TPIMS-8 has demonstrated exceptional curative ability against resistant bacterial biofilm infections in vivo with minimal side effects. Furthermore, it is applied to clinical samples from infected patients and the results indicated that TPIMS-8 is able to achieve excellent bacterial-specific detection and superior killing of drug-resistant bacteria even in complex systems, demonstrating its great potential for clinical applications. This study presents a promising foundation for the development of advanced antimicrobial therapeutics targeting multidrug-resistant bacteria and biofilm-associated infections.     

Short Synthetic β‐Sheet Forming Peptide Amphiphiles as Broad Spectrum Antimicrobials with Antibiofilm and Endotoxin Neutralizing Capabilities

Although naturally occurring membrane lytic antimicrobial peptides (AMPs) and their analogs hold enormous promise for antibiotics‐resistant infectious disease therapies, significant challenges such as systemic toxicities, long peptide sequences, poor understanding of structure‐activity relationships, and the potential for compromising innate host defense immunity have greatly limited their clinical applicability. To improve the clinical potential of AMPs, a facile approach is adopted to design a series of short synthetic β‐sheet folding peptide amphiphiles comprised of short recurring (X₁Y₁X₂Y₂)_n‐NH₂ sequences, where X₁ and X₂: hydrophobic residues (Val, Ile, Phe or Trp), Y₁ and Y₂: cationic residues (Arg or Lys), and n: number of repeat units; with systematic variations to the cationic and hydrophobic residues to obtain optimized AMP sequences bearing minimal resemblance to naturally occurring sequences. The designed β‐sheet forming peptides exhibit broad spectrum antimicrobial activities against various clinically relevant microorganisms, including Gram‐positive Staphylococcus epidermidis and Staphylococcus aureus, Gram‐negative Escherichia coli and Pseudomonas aeruginosa, and yeast Candida albicans, with excellent selectivities for microbial membranes. Optimal synthetic peptides with n = 2 and n = 3 repeat units, i.e., (IRIK)₂‐NH₂ and (IRVK)₃‐NH₂, efficiently inhibit sessile biofilm bacteria growth leading to biomass reduction. Additionally, sequences with n = 3 repeat units effectively neutralize endotoxins while causing minimal cytotoxicities. Taken together, these findings clearly demonstrate that the rationally designed synthetic β‐sheet folding peptides are highly selective, non‐cytotoxic at antimicrobial levels and have tremendous potential for use as broad spectrum antimicrobial agents to overcome multidrug resistance in a wide range of localized, systemic, or external therapeutic applications.     

Fracture of Sn-Ag-Cu Solder Joints on Cu Substrates: I. Effects of Loading and Processing Conditions

During service, microcracks form inside solder joints, making microelectronic packages highly prone to failure on dropping. Hence, the fracture behavior of solder joints under drop conditions at high strain rates and under mixed-mode conditions is a critically important design consideration for robust joints. This study reports on the effects of joint processing and loading conditions on the microstructure and fracture response of Sn-3.8%Ag-0.7%Cu (SAC387) solder joints attached to Cu substrates. The impact of parameters which control the microstructure (reflow condition, aging) as well as loading conditions (strain rate and loading angle) are explicitly studied. A methodology based on the calculation of the critical energy release rate, G _C, using compact mixed-mode (CMM) samples was developed to quantify the fracture toughness of the joints under conditions of adhesive (i.e., interface-related) fracture. In general, higher strain rate and increased mode-mixity resulted in decreased G _C. G _C also decreased with increasing dwell time at reflow temperature, which produced a thicker intermetallic layer at the solder–substrate interface. Softer solders, produced by slower cooling following reflow, or post-reflow aging, showed enhanced G _C. The sensitivity of the fracture toughness to all of the aforementioned parameters reduced with an increase in the mode-mixity. Fracture mechanisms, elucidating the effects of the loading conditions and process parameters, are briefly highlighted.     

Nonchemotherapic and Robust Dual‐Responsive Nanoagents with On‐Demand Bacterial Trapping,Ablation, and Release for Efficient Wound Disinfection

Recent emerged antibacterial agents provide enormous new possibilities to replace antibiotics in fighting bacterial infectious diseases. Although abundant types of nanoagents are developed for preventing pathogen colonization, however, rationally design of nonchemotherapic, robust, and clinical‐adaptable nanoagents with tunable bacterial trap and killing activities remains a major challenge. Here, a demonstration of controlling the trap, ablation, and release activities of pathogenic bacteria via stimulus‐responsive regulatory mechanism is reported. First, temperature‐sensitive polymer brush is chemically grown onto carbon nanotube–Fe₃O₄, whereby the synthesized nanoagents can transfer from hydrophilic dispersion to hydrophobic aggregation upon near‐infrared light irradiation, which thus controls the bacterial trap, killing, and detaching. In turn, the formed aggregations will serve as localized heating sources to enhance photothermal ablation of bacteria. Systematically antibacterial experiments and mouse wound disinfection demonstrate the ultrarobust and recyclable disinfection capability of nanoagents with nearly 100% killing ratio to Staphylococcus aureus. Overall, for the first time, we represent a pioneering study on designing nonchemotherapic and robust dual‐responsive nanoagents that can sensitively and reversibly trap, inactivate, and detach bacteria. We envision that such nanoagents will not only have potential applications in pathogenic bacteria prevention but also provide a new pathway for wound disinfection, implant sterilization, and also live bacteria transportation.     

Nonoxidized MXene Quantum Dots Prepared by Microexplosion Method for Cancer Catalytic Therapy

Nanocatalysts based on Fenton or Fenton‐like reactions for amplification of intracellular oxidative stress has become a frontier research area of tumor precise therapy. However, the major translational challenges are low catalytic efficiency, poor biocompatibility, and even potential toxicities. Here, a Ti‐based material with excellent biocompatibility is proposed for cancer treatment. The nonoxidized MXene‐Ti₃C₂T_x quantum dots (NMQDs‐Ti₃C₂T_x) are successfully prepared by a self‐designed microexplosion method. Surprisingly, it has an apparent inhibitory and killing effect on cancer cells, and excellent biocompatibility with normal cells. Moreover, the suppression rate of NMQDs‐Ti₃C₂T_x on xenograft tumor models can reach 91.9% without damaging normal tissues. Mechanistically, the Ti³⁺ of NMQDs‐Ti₃C₂T_x can react with H₂O₂ in the tumor microenvironment and high‐efficiently produce excessive toxic hydroxyl radicals to increase tumor microvascular permeability to synergistically kill cancer cells. This work should pave the way for tumor catalytic therapy applications of Ti‐based material as a promising and safer route.     

Bioinspired Intrinsic Versatile Hydrogel Fabricated by Amyloidal Toxin Simulant-Based Nanofibrous Assemblies for Accelerated Diabetic Wound Healing

Persistent microbial infection and decreased neovascularization are common issues associated with diabetic wound treatment. Hydrogel dressings that offer intrinsic antibacterial and angiogenesis-inducing may substantially avoid the use of antibiotics or angiogenic agents. Herein, a versatile hydrogel is fabricated using an amyloid-derived toxin simulant (Fmoc-LFKFFK-NH₂, FLN) as building blocks, inspired by the defense strategy of Staphylococcus aureus (S. aureus). The simulant assemblies of the hydrogel function as both matrix components and functional elements for diabetic wound treatment. The hydrogel undergoes quick assembly from random monomers to nanofibrils with abundant b-sheet driven by multiple non-covalent interactions. The developed hydrogel demonstrates excellent biocompatibility and accelerates angiogenesis via hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor A (VEGFA) signaling as a consequence of its amyloidal structure. The simulant-based nanofibrils endow the hydrogel with broad-spectrum antibacterial activity dominated by a membrane-disruption mechanism. In addition, the hydrogel exhibits excellent performance compared with the commercial hydrogel Prontosan in accelerating wound healing of diabetic mice infected with methicillin-resistant S. aureus (MRSA). This study highlights the fabrication of a single component and versatile hydrogel platform, thereby avoiding the drug-related side effects and complicated preparations and demonstrating its profound potential as a clinical dressing for the management of microbe-infected diabetic wounds.     

PtCu Nanosonosensitizers with Inflammatory Microenvironment Regulation for Enhanced Sonodynamic Bacterial Elimination and Tissue Repair

Sonodynamic therapy (SDT) is considered a reliable replacement therapy to overcome the resistance to antibiotics and the limited tissue penetration of traditional photo-induced therapy. Herein, ultrasmall platinum-copper alloy nanoparticles (PtCu NPs) modified with poly (maleic anhydridealt-1-octadecene)-polyethylene glycol (C₁₈PMH-PEG) with high sonodynamic activity, strong catalytic ability, and good glutathione (GSH) depletion performance are synthesized for highly efficient bacterial elimination. PtCu NPs obtained through a thermal decomposition approach can generate high toxic singlet oxygen (¹O₂) under ultrasound (US) irradiation, showing good sonodynamic performance. Meanwhile, the partial oxygenation formed on the surface of PtCu NPs endows them with good Fenton-like catalytic performance and superior GSH-depleting ability, thus enhancing reactive oxygen species (ROS) generation. In vitro experiments confirm that the synthesized PtCu- NPs can not only efficiently kill both gram-positive and gram-negative bacteria but also eliminate staphylococcus aureus (S. aureus) infection through ROS generation and then accelerate wound healing in the S. aureus-infected wound model. Meanwhile, the copper ions released from PtCu NPs can promote cell migration and angiogenesis through the up-regulation of hypoxia inducible factor (HIF-1α) and platelet endothelial cell adhesion molecule (CD31). Finally, the S. aureus-induced deep-seated osteomyelitis infection and bone destruction were successfully inhibited by the PtCu-mediated combination therapy. Our work highlights a novel SDT strategy for enhanced sonodynamic bacteria elimination and tissue repair.