Precise targeted delivery of antibiotics to infected sites is crucial for enhancing therapeutic efficacy and minimizing side effects. In this work, we present magnetic hydrogel-based microrobots for active antibiotic delivery to achieve targeted bacterial elimination. These microrobots comprise a poly(acrylic acid-co-acrylamide) hydrogel microspheres encapsulating Fe3O4 nanoparticle chains. The hydrogel scaffold offers abundant spaces and binding sites for high-capacity loading of vancomycin via electrostatic interactions. The embedded Fe3O4 nanochains enable magnetic propulsion. Under a rotating magnetic field (Hr(t)), the microrobots can actively deliver vancomycin to infected sites via their swarming motions, and then eliminate the bacteria (e.g., Staphylococcus aureus) utilizing their sustainable vancomycin release on site. These hydrogel-based microrobots hold great promise as a motile antibacterial platform to treat infectious diseases.

Infected wounds present a significant clinical challenge, exacerbated by antibiotic resistance, which complicates effective treatment. This study introduces a hydrogel (CC/AP@CM) embedded with core-shell bioactive glass nanoparticles designed for the controlled, sequential release of copper (Cu2+) and magnesium (Mg2+) ions. The hydrogel is crosslinked via a Schiff base reaction, endowing it with injectable, self-healing, and adhesive properties. Notably, the bilayer structure of the bioactive glass within the hydrogel allows an initial release of Cu2+ ions to trigger an early-stage pro-inflammatory and antimicrobial response, followed by Mg2+ ions that support tissue repair and an anti-inflammatory environment. This design aligns with natural wound healing stages, promoting a shift in macrophage polarization from the M1 to M2 phenotype, effectively balancing antibacterial defense with tissue regeneration. The hydrogel demonstrated robust antibacterial efficacy against MRSA, increased angiogenesis, and enhanced fibroblast proliferation and migration in vitro. In a murine wound model, it significantly accelerated wound closure and immune activation, including responses from dendritic cells and T cells. These findings suggest that this hydrogel, through its stage-specific immunomodulatory properties and temporally controlled ion release, offers a promising strategy for treating complex wound infections, supporting both immune defense and tissue healing.

Osteomyelitis caused by Staphylococcus aureus (S. aureus) is difficult to cure with antibiotics or phototherapy. Microwave (MW) has become a promising method for treating deep tissue infections due to its strong penetration ability, however, the effects of MW dynamics still need to be improved to achieve rapid and effective treatment. In this work, tin selenide/polypyrrole (SnSe/PPy) nanocomposites with MW thermoelectric catalytic performance are successfully prepared, and their ideal thermal production capability stems from increased dielectric loss, including interfacial polarization and conductive loss, as well as magnetic loss. Furthermore, the enhanced interchain electronic transport of PPy and the phonon scattering effect have improved the thermoelectric performance of SnSe/PPy. Under MW cyclic irradiation, SnSe/PPy can convert the generated temperature difference into electrical energy and further promote the ionization of sodium species, the plasma and electrons react with O2 to produce superoxide anion (·O2 -), enabling SnSe/PPy to rapidly increase the temperature and effectively eliminate S. aureus infection. After irradiated circularly by MW for 20 min, the antibacterial effect of SnSe/PPy can reach 99.46 ± 0.11%. Considering the remarkable antibacterial effectiveness and excellent biosafety, it is believed that it provides new insights into the design of MW thermoelectric catalysis antimicrobial materials.

The global rise in infectious diseases and antibiotic overuse exacerbate bacterial drug resistance, particularly in multidrug-resistant pathogens like methicillin-resistant Staphylococcus aureus (MRSA). While plant-derived flavones exhibit multi-target antibacterial mechanisms that overcome resistance, their therapeutic application remains constrained by poor aqueous dispersibility and stability. Herein, a luteolin-iron complex (Lut-Fe3⁺) is engineered through a facile coordination approach, where Fe3⁺ facilitates d-orbital splitting and generation of high-spin electrons. This octahedral complex demonstrates exceptional water dispersibility and exhibits broad-spectrum absorption across ultraviolet to microwave (MW) frequencies. Lut-Fe3⁺ demonstrates dual antimicrobial modalities: long-term antisepsis in the dark and rapid sterilization under light/MW irradiation. This multi-functional complex is further combined with various methods to develop therapeutic strategies for bacterial infections at different depths. Notably, the Lut-Fe3⁺ is engineered into an MW-responsive nebulization system, achieving effective eradication of MRSA-induced deep-tissue pneumonia in mice.

Microwave ablation, as a critical minimally invasive technique for tumor treatment, remains challenging in achieving an optimal balance between incomplete and excessive ablation. In addition to selectively elevating the temperature of tumor lesions through the microwave thermal effect, microwave-responsive nanoparticles can also improve the efficacy of single-session ablation by generating reactive oxygen species (ROS) via the microwave dynamic effect, thereby mitigating the thermal damage to normal tissues caused by high temperature. In this study, ultra-small gold nanoparticles anchored hollow mesoporous carbon nanoparticles (HMCNs) are loaded with hemoglobin (Hb) to serve as microwave ablation nano-sensitizers (HMCN/Au@Hb), which will amplify the microwave dynamic effect by alleviating the hypoxic microenvironment of tumors. Upon microwave irradiation, HMCN/Au@Hb not only improves the microwave-thermal conversion efficiency of tumor lesion but also promotes the ROS generation by increasing oxygen content in the hypoxic tumor microenvironment. More importantly, we found that the hypoxia relief will improve the antitumor response and further enhance the clearance of residual tumor after ablation. Nearly complete ablation was achieved in certain tumor-bearing mice, with no recurrence of the primary tumor observed up to 33 days post-ablation. In comparison to traditional microwave ablation, the survival time of the tumor-bearing mice was significantly extended. Therefore, this work presents an innovative ablation sensitization strategy based on the hypoxia relief and provides a nanosensitizer for microwave ablation integrating great microwave-thermal and dynamic effects along with immune modulation capabilities.

Osteomyelitis poses substantial therapeutic challenges due to the prevalence of multidrug-resistant bacterial infections and associated inflammation. Current treatment regimens often rely on a combination of corticosteroids and antibiotics, which can lead to complications and impede effective bacterial clearance. In this study, we present CADP-10, a Cecropin A-derived peptide, designed to target methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Escherichia coli (MRE), while simultaneously addressing inflammatory responses. CADP-10 self-assembles into nanobacterial net (NBacN) that selectively identify and bind to bacterial endotoxins (LPS and LTA), disrupting membrane integrity and depolarizing membrane potential, which culminates in bacterial death. Importantly, these NBacN are bound to LPS and LTA from dead bacteria, preventing their engagement with TLR receptors and effectively blocking downstream inflammatory pathways. Our assessments of CADP-10 demonstrate good biosafety in both in vitro and in vivo models. Notably, in a rabbit osteomyelitis model, CADP-10 eliminated MRSA-induced bone infections, mitigated inflammation, and promoted bone tissue regeneration. This research highlights the potential of CADP-10 as a multifunctional antimicrobial agent for the management of infectious inflammatory diseases.

Bone defects resulting from trauma, tumors, or other injuries significantly impact human health and quality of life. However, current treatments for bone defects are constrained by donor shortages and immune rejection. Bone tissue engineering has partially alleviated the limitations of traditional bone repair methods. The development of smart biomaterials that can respond to external stimuli to modulate the biofunctions has become a prominent area of research. Ultrasound technology is regarded as an optimal "remote controller" and "trigger" for bone repair biomaterials. This review reports the comprehensive and systematic overview of ultrasound-responsive bone repair smart biomaterials. It presents the fundamental theories of bone repair, the definition of ultrasound, and its applications. Furthermore, the review summarizes the ultrasound effect mechanisms of biomaterials and their roles in bone repair, including detailed studies on anti-inflammation, immunomodulation, and cell therapy. Finally, the advantages of ultrasound-responsive smart biomaterials and their future prospects in this field are discussed.

Thermal ablation (TA) is widely used for clinical treatment of various cancers. However, TA often struggles to efficiently kill tumor cells without injuring adjacent normal tissues/cells, leading to thermo-mediated tumor relapse and metastasis, owing to the immunosuppressive microenvironment surrounding residual tumor cells. In this study, a temperature-sensitive ionic liquid composed of lipoic acid and choline (LACH/PNA) is developed as a multifunctional TA sensitizer to suppress tumor metastasis induced by incomplete microwave ablation. LACH/PNA exhibits a high diffusion coefficient by disrupting the tumor matrix and modulating cancer-associated fibroblasts, thereby facilitating heat and mass transfer in tumors. LACH/PNA demonstrates greater cytotoxicity toward hepatoma cells than on normal hepatocytes with this effect further intensified by thermal treatment. These findings highlight LACH/PNA as a promising multifunctional sensitizer for clinical chemoablation-microwave ablation synergy.

Chronic osteomyelitis caused by implant infections is a common complication following orthopedic surgery. Preventing bacterial infection and simultaneously improving bone regeneration are the key for osteomyelitis. Current treatments include systemic antibiotics and multiple surgical interventions, but the strategies available for treatment are limited. In this study, a multifunctional engineered Bacillus subtilis (B. sub) hydrogel with sulfasalazine (SSZ) is developed to treat methicillin-resistant Staphylococcus aureus (MRSA) infection and anti-inflammatory and promote bone regeneration. B. sub in alginate hydrogels protects B. sub from being cleared by the host immune system while allowing the release of its bioactive substances, including antibacterial peptides and anti-inflammatory agents such as SSZ. The results show that the engineered probiotic hydrogels exhibit excellent antibacterial efficacy against MRSA (97 %) and prevent the development of bacterial resistance. The antibacterial effect is primarily mediated through the secretion of bioactive peptides by B. sub, which not only inhibit MRSA growth but also reduce the likelihood of resistance development. Meanwhile, the probiotic hydrogel has a greater ability to induce M2 polarization of macrophages and promote angiogenesis, resulting in enhanced osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs) and thus enhancing bone regeneration. This engineered probiotic hydrogel offers a promising strategy by simultaneously combating bacterial infection and enhancing osteogenic differentiation for chronic osteomyelitis.

Implant-associated infections (IAIs) are refractory to elimination, and the local immunosuppressive microenvironment (IME) exacerbates therapeutic difficulties, ultimately causing persistence and relapse. Therefore, exploring immunostrengthening treatments holds great promise for reversing IME and thoroughly eradicating chronic or repetitive infections. Bacterial outer membrane vesicles (OMVs) have emerged as potential immunostimulatory candidates; however, they lack active targeting capabilities and cause non-specific inflammatory side effects. In this study, bone marrow-derived mesenchymal stem cells (BMSCs) are genetically engineered to overexpress CXCR4 and isolated cell membranes (mBMSCCXCR4) for hybridization with OMVs derived from Escherichia coli (E. coli) to produce nanovesicles (mBMSCCXCR4@OMV). The resulting mBMSCCXCR4@OMV nanovesicles demonstrate excellent bone marrow targeting capability and are effectively taken up by bone marrow-derived macrophages, triggering the efficient transition to pro-inflammatory M1 status through TLR/NF-κB pathway. This alteration promotes innate bactericidal capacity and antigen presentation. Subsequent activation of T and B cells and inhibition of myeloid-derived suppressor cells (MDSCs) facilitated in vivo adaptive immunity in mouse models. Additionally, mBMSCCXCR4@OMV boosted memory B cell and bacteria-specific antibody responses. Together, these data highlight the potential of mBMSCCXCR4@OMV to eradicate complicated IAIs and provide whole-stage protection against postsurgical relapse, thus marking a significant immunotherapeutic advancement in the post-antibiotic era.

Bone-related diseases pose a major challenge in contemporary society, with significant implications for both health and economy. Copper, a vital trace metal in the human body, facilitates a wide range of physiological processes by being crucial for the function of proteins and enzymes. Numerous studies have validated copper's role in bone regeneration and protection, particularly in the development and expansion of bone collagen. Owing to copper's numerous biological advantages, an increasing number of scientists are endeavoring to fabricate novel, multifunctional copper-containing biomaterials as an effective treatment strategy for bone disorders. This review integrates the current understanding regarding the biological functions of copper from the molecular and cellular levels, highlighting its potential for bone regeneration and protection. It also reviews the novel fabrication techniques for developing copper-containing biomaterials, including copper-modified metals, calcium phosphate bioceramics, bioactive glasses, bone cements, hydrogels and biocomposites. The fabrication strategies and various applications of these biomaterials in addressing conditions such as fractures, bone tumors, osteomyelitis, osteoporosis, osteoarthritis and osteonecrosis are carefully elaborated. Moreover, the long-term safety and toxicity assessments of these biomaterials are also presented. Finally, the review addresses current challenges and future prospects, in particular the regulatory challenges and safety issues faced in clinical implementation, with the aim of guiding the strategic design of multifunctional copper-based biomaterials to effectively manage bone-related diseases.

Osteomyelitis is a serious inflammatory disease mostly caused by bacterial infections. It is necessary to simultaneously eradicate bacterial cells and inhibit inflammation in treating osteomyelitis. Herein, we design an innovative zinc ion (Zn2+)-based nano delivery system for the management of osteomyelitis. Taking advantage of the coordination self-assembly of Zn2+, quercetin (QU), and ε-poly-L-lysine (EPL), Zn2+-containing nanoparticles (denoted as ZQE NPs) are prepared. ZQE NPs are spherical nanoparticles with amorphous structures. They are stable in the physiological neutral environment but can be dissociated in an acidic microenvironment of infection sites. Since Zn2+ is encapsulated into ZQE NPs by coordination interaction, the deactivation of Zn2+ by proteins can be effectively avoided. Therefore, ZQE NPs can maintain excellent bactericidal activity in a protein-rich environment, while dissociative Zn2+ doesn't exhibit obvious bactericidal ability. Meanwhile, ZQE NPs are highly effective at scavenging intracellular reactive oxygen species (ROS) and inhibiting pro-inflammatory cytokines, due to the strong anti-inflammatory effects of QU and Zn2+. The in vivo therapeutic efficacy of ZQE NPs is assessed using a rat model of methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis. Results demonstrate that ZQE NPs effectively eradicate bacterial cells and reduce inflammation in vivo, thereby promoting osteogenesis and recovery of osteomyelitis.

Cuproptosis exhibits enormous application prospects in treatment. However, cuproptosis-based therapy is impeded by the limited intracellular copper ions, the nonspecific delivery, uncontrollable release, and chelation of endogenous overproduced glutathione (GSH). In this work, an ultrasound-triggered nanosonosensitizer (p-TiO2-Cu(I)) was constructed for Cu(I) delivery, on-demand release, GSH consumption, and deeper tissue response. When the nanomedicine was internalized into the tumor cells, ultrasound (US) induced the nanosonosensitizer to produce reactive oxygen species (ROS) to achieve sonodynamic therapy (SDT). GSH, acting as a hole trapping agent, improved the efficiency of SDT. Meanwhile, the downgrade of GSH was beneficial to cuproptosis and oxidative damage-based SDT in return. What is more, the US could regulate the release behavior of Cu(I). Cu(I) bonded to mitochondrial proteins and then aggregated the lipoylated protein, bringing about the turbulence of the tricarboxylic acid cycle. The combination of SDT and cuproptosis showed high matching to induce efficient cuproptosis and may inspire other cuproptosis-based nanosonosensitizer designs.

Traditional chemical pesticides are easily lost by surface runoff and only small quantities reach the target, thus causing serious environmental pollution. In this work, dinotefuran@zeolitic imidazolate framework-8@polydopamine@zein (DNF@ZIF-8@PDA@zein), was constructed to deliver DNF with pH and enzyme double response of release, thereby achieving targeted release and efficient long-term pest control.

DNF@ZIF-8@PDA@zein was synthesized with three hydrated diameters (249.73 ± 9.99 nm, 142.94 ± 5.63 nm and 75.16 ± 4.66 nm, respectively). The release of DNF from DNF@ZIF-8@PDA@zein after 28 h was significantly higher at pH 5.0 (89.22 ± 7.18%) compared to that at pH 8 (81.8 ± 6.11%). Protease-assisted release of DNF was notably higher than that without protease (pH 5: 89.22 ± 5.55% versus 27.19 ± 3.22%; pH 8: 81.8 ± 6.11% versus 25.39 ± 3.87%). The stimuli-responsive release of DNF from DNF@ZIF-8@PDA@zein increased with decreased particle size due to increased pore size, reduced binding forces (i.e., weaker π-π stacking, hydrogen bonding, and Zn-N covalent bonding), and the shortening of diffusion path, leading to faster disintegration and drug release. Additionally, the anti-photolysis ability of DNF@ZIF-8@PDA@zein was 3.2 times that of pure DNF. The insecticidal activity improved with smaller nanoparticles due to higher drug release rate and greater inhibition of detoxification enzyme activity by more zinc ion (Zn2+) dissolution.

The pH and enzyme dual-responsive release as well as insecticidal activity of DNF@ZIF-8@PDA@zein increase with decreased nanoparticle size, showing effective pest management in long-term and potential application prospects in sustainable agriculture. © 2024 Society of Chemical Industry.

Bacterial infections have emerged as a major threat to global public health. The effectiveness of traditional antibiotic treatments is waning due to the increasing prevalence of antimicrobial resistance, leading to an urgent demand for alternative antibacterial technologies. In this context, antibacterial nanomaterials have proven to be powerful tools for treating antibiotic-resistant and recurring infections. Targeting nanomaterials not only enable the precise delivery of bactericidal agents but also ensure controlled release at the infection site, thereby reducing potential systemic side effects. This review collates and categorizes nanomaterial-based responsive and precision-targeted antibacterial strategies into three key types: exogenous stimuli-responsive (including light, ultrasound, magnetism), bacterial microenvironment-responsive (such as pH, enzymes, hypoxia), and targeted antibacterial action (involving electrostatic interaction, covalent bonding, receptor-ligand mechanisms). Furthermore, we discuss recent advances, potential mechanisms, and future prospects in responsive and targeted antimicrobial nanomaterials, aiming to provide a comprehensive overview of the field's development and inspire the formulation of novel, precision-targeted antimicrobial strategies.

Multi-walled carbon nanotubes (MWCNTs) were used as carriers for silver nanoparticles (AgNPs). In this process, MWCNTs were coated with mesoporous silica (MWCNT-Silica) for uniform and regular loading of AgNPs on the MWCNTs. In addition, astaxanthin (AST) extract was used as a reducing agent for silver ions to enhance the antioxidant, antibiofilm, and anticancer activities of AgNPs. In this process, AST was extracted from Haematococcus pluvialis (H. pluvialis) and processed by hot melt extrusion (HME) to enhance the AST content of H. pluvialis. AST has strong antioxidative properties, which leads to anticancer activity. In addition, AgNPs are well known for their strong antibacterial properties. The antibiofilm and anticancer effects were studied comprehensively by loading the AST AgNPs onto MWCNT-Silica.

AgNPs-loaded MWCNT-silica (MWCNT-Ag) was prepared through the binding reaction of TSD and silanol groups and the aggregation interaction of Ag and TSD. To enhance the antioxidant, antibiofilm, and anticancer activities of AgNPs, HME-treated H. pluvialis extract (HME-AST) was used as a reducing solution of silver ions. The increased AST content of HME-AST was confirmed by high-performance liquid chromatography (HPLC) analysis, and the total phenol and flavonoid content analysis confirmed that HME enhanced the active components of H. pluvialis. The antibiofilm activity of MWCNT-AST was investigated by biofilm inhibition and destruction test, SEM, and CLSM analysis, and the anticancer activity was investigated by WST assay, fluorescent staining analysis, and flow cytometry analysis.

MWCNT-AST showed higher antioxidant activity and antibiofilm activity than MWCNT-Ag against E. coli, S. aureus, and methicillin-resistant S. aureus (MRSA). MWCNT-AST showed higher anticancer activity against breast cancer cells (MDA-MB-231) than MWCNT-Ag, and lower toxicity in normal cells HaCaT and NIH3T3.

MWCNT-AST exhibits higher antioxidant, antibiofilm, and anticancer activities than MWCNT-Ag, and exhibits lower toxicity to normal cells.

Eradication of osteomyelitis caused by bacterial infections is still a major challenge. Microwave therapy has the inherent advantage of deep penetration in curing deep tissue infections. However, the antibacterial efficiency of sensitizers is limited by the weak energy of microwaves. Here, a hybrid heterojunction system (Fe3O4/CuS/Emo) is designed for curing bacterially infected osteomyelitis. As an enhanced microwave sensitizer, it shows supernormal microwave response ability. Specifically, Fe3O4 acts as a matrix to mediate magnetic loss. After CuS loading, the heterogeneous interface forms induce significant interfacial polarization, which increasing dielectric loss. On the basis of the heterojunction formed by the two semiconductors, emodin is innovatively introduced to modify it. This integration not only accelerates the movement of charge carriers but also enhances polarization loss due to the numerous functional groups present on the surface. This further optimizes the microwave thermal and catalytic response. In addition, the unique anti-inflammatory properties of emodin confer the ability of hybrid heterojunction to regulate the immune microenvironment. In vivo studies reveal that heterojunction modified by emodin programmed elimination of bacteria and regulation of the immune microenvironment. It offers a revolutionary approach to the treatment of bacterial osteomyelitis.

The biofilm-induced "relatively immune-compromised zone" creates an immunosuppressive microenvironment that is a significant contributor to refractory infections in orthopedic endophytes. Consequently, the manipulation of immune cells to co-inhibit or co-activate signaling represents a crucial strategy for the management of biofilm. This study reports the incorporation of Mn2+ into mesoporous dopamine nanoparticles (Mnp) containing the stimulator of interferon genes (STING) pathway activator cGAMP (Mncp), and outer wrapping by M1-like macrophage cell membrane (m-Mncp). The cell membrane enhances the material's targeting ability for biofilm, allowing it to accumulate locally at the infectious focus. Furthermore, m-Mncp mechanically disrupts the biofilm through photothermal therapy and induces antigen exposure through photodynamic therapy-generated reactive oxygen species (ROS). Importantly, the modulation of immunosuppression and immune activation results in the augmentation of antigen-presenting cells (APCs) and the commencement of antigen presentation, thereby inducing biofilm-specific humoral immunity and memory responses. Additionally, this approach effectively suppresses the activation of myeloid-derived suppressor cells (MDSCs) while simultaneously boosting the activity of T cells. Our study showcases the efficacy of utilizing m-Mncp immunotherapy in conjunction with photothermal and photodynamic therapy to effectively mitigate residual and recurrent infections following the extraction of infected implants. As such, this research presents a viable alternative to traditional antibiotic treatments for biofilm that are challenging to manage.

Chemodynamic therapy (CDT) guided by Fenton chemistry and iron-containing materials can induce ferroptosis as a prospective cancer treatment method, but the inefficient Fe3+/Fe2+ conversion restricts the monotherapeutic performances. Here, an iron-based nanoplatform (Fe3O4-SRF@FeTA) including a magnetic core and a reductive film is developed for combined CDT and photothermal therapy (PTT) through ferroptosis augmentation. The inner iron oxide core serves as a photothermal transducer, a magnet-responsive module, and an iron reservoir for CDT. The coated Fe3+-tannic acid film (FeTA) provides extra iron and reductants for Fe3+/Fe2+ conversion acceleration, and functions as a door keeper for the pH- and light-responsive release of the embedded ferroptosis inducer sorafenib (SRF). The in vitro results demonstrate that the iron-based nanocomplexes promote the production of lipid peroxide through the amplified Fenton activity, and downregulate glutathione involved in lipid peroxide repair system through the responsively released SRF. Upon accumulation in tumor by magnetic targeting and sequential laser irradiation locoregionally, Fe3O4-SRF@FeTA nanocomplexes present prominent in vivo anticancer efficacy by leveraging PTT and CDT-enhanced ferroptosis.

Staphylococcus aureus (S. aureus)-infected osteomyelitis is a deep tissue infection that cannot be effectively treated with antibiotics. Microwave (MW) thermal therapy (MTT) and MW dynamic therapy (MDT) based on MW-responsive materials are promising for the therapy of bacteria-infected osteomyelitis occurring in deep tissues that cannot be effectively treated with antibiotics. In this work, the MW-responsive system of carbon nanotubes (CNTs)/Prussian blue (PB)/puerarin (Pue) with stable network-like structures is constructed. The PB is grown in situ on the CNTs, and its introduction not only reduces the aggregation of the network-like structures of the CNTs, but the large specific surface area and mesoporous structure can also provide many active sites for the adsorption of oxygen and polar molecules. Pue is a natural anti-inflammatory material that reduces inflammation at the infection site. The composite of the CNTs and PB avoids the skin effect and thus can improve dielectric and reflection losses. The MW thermal response of CNTs/PB/Pue is mainly due to the occurrence of reflection loss, dielectric loss, multiple reflections and scattering, interface polarization, and dipole polarization. In addition, under MW irradiation, the CNTs/PB/Pue can produce reactive oxygen species (ROS), such as singlet oxygen (1O2), hydroxyl radical (·OH).

Electromagnetic (EM) wave pollution and thermal damage pose serious hazards to delicate instruments. Functional aerogels offer a promising solution by mitigating EM interference and isolating heat. However, most of these materials struggle to balance thermal protection with microwave absorption (MA) efficiency due to a previously unidentified conflict between the optimizing strategies of the two properties. Herein, this study reports a solution involving the design of a carbon-based aerogel called functional carbon spring (FCS). Its unique long-range lamellar multi-arch microstructure enables tunable MA performance and excellent thermal insulation capability. Adjusting compression strain from 0% to 50%, the adjustable effective absorption bandwidth (EAB) spans up to 13.4 GHz, covering 84% of the measured frequency spectrum. Notably, at 75% strain, the EAB drops to 0 GHz, demonstrating a novel "on-off" switchability for MA performance. Its ultralow vertical thermal conductivity (12.7 mW m-1 K-1) and unique anisotropic heat transfer mechanism endow FCS with superior thermal protection effectiveness. Numerical simulations demonstrate that FCS outperforms common honeycomb structures and isotropic porous aerogels in thermal management. Furthermore, an "electromagnetic-thermal" dual-protection material database is established, which intuitively demonstrates the superiority of the solution. This work contributes to the advancement of multifunctional MA materials with significant potential for practical applications.

Microwave (MW) therapy is an emerging therapy with high efficiency and deep penetration to combat the crisis of bacterial resistance. However, as the energy of MW is too low to induce electron transition, the mechanism of MW catalytic effect remains ambiguous. Herein, a cerium-based metal-organic framework (MOF) is fabricated and used in MW therapy. The MW-catalytic performance of CeTCPP is largely dependent on the ions in the liquid environment, and the electron transition is achieved through a "tribovoltaic effect" between water molecules and CeTCPP. By this way, CeTCPP can generate reactive oxygen species (ROS) in saline under pulsed MW irradiation, showing 99.9995 ± 0.0002% antibacterial ratio against Staphylococcus aureus (S. aureus) upon two cycles of MW irradiation. Bacterial metabolomics further demonstrates that the diffusion of ROS into bacteria led to the bacterial metabolic disorders. The bacteria are finally killed due to "amino acid starvation". In order to improve the applicability of CeTCPP, It is incorporated into alginate-based hydrogel, which maintains good MW catalytic antibacterial efficiency and also good biocompatibility. Therefore, this work provides a comprehensive instruction of using CeTCPP in MW therapy, from mechanism to application. This work also provides new perspectives for the design of antibacterial composite hydrogel.

Due to their poor light penetration, photothermal therapy and photodynamic therapy are ineffective in treating deep tissue infections, such as osteomyelitis caused by Staphylococcus aureus (S. aureus). Here, a microwave (MW)-responsive magnetic targeting composite system consisting of ferric oxide (Fe3O4)/Prussian blue (PB) nanoparticles, gentamicin (Gent), and biodegradable poly(lactic-co-glycolic acid) (PLGA) is reported. The PLGA/Fe3O4/PB/Gent complex is used in combination with MW thermal therapy (MTT), MW dynamic therapy (MDT), and chemotherapy (CT) to treat acute osteomyelitis infected with S. aureus-infected. The powerful antibacterial effect of the PLGA/Fe3O4/PB/Gent is determined by the synergistic effects of heat and reactive oxygen species (ROS) generation by the Fe3O4/PB nanoparticles under MW irradiation and the effective release of Gent at the infection site via magnetic targeting. The antibacterial mechanism of the PLGA/Fe3O4/PB/Gent under MW irradiation is analyzed using bacterial transcriptome RNA sequencing. The MW heat and ROS reduce the activity of the protein transporters on the bacterial membrane, along with the transport of various ions and the acceleration of phosphate metabolism, which can lead to increased permeability of the bacterial membrane, damage the ribosome and DNA, and accompany the internal protein efflux of the bacteria, thus effectively killing the bacteria.

High-frequency electronic response governs a broad spectrum of electromagnetic applications from radiation protection, and signal compatibility, to energy recovery. Despite various efforts to manage electric conductivity, dynamic control over dielectric polarization for real-time electromagnetic modulation remains a notable challenge. Herein, an electrochemical lithiation-driven hierarchical disordering strategy is demonstrated for actively modulating electromagnetic properties. The controllable formation and diffusion of coherent interfaces and cation vacancies tailor the coupling of atomic electric field and thus the locally polarized domains, which leads to the reversible electromagnetic transparency/absorption switching with a tunable range of -0.8--20.4 dB for the reflection loss and a broad operation bandwidth of 4.6 GHz. Compared to traditional methods of heteroatomic doping, hydrogenation, mechanical deformation, and phase transition, the electrochemical strategy shows a larger regulation scope of dielectric permittivity with the maximum increase ratios of 260% and 1950% for real and imaginary parts, respectively. This enables the construction of various device architectures including the adaptive window and pixelated metasurface. The results offer opportunities to achieve intelligent electromagnetic devices and pave an avenue to rejuvenate various electromagnetic functions of semiconductive oxides.

Osteomyelitis with high mortality and disability rates is a common clinical disease caused by a bacterial infection that is difficult to cure. Considering the stubborn nature and depth of tissue infection, rapid and effective treatments for osteomyelitis remain an enormous challenge. Calcium hydride (CaH2), as efficient hydrogen/alkaline/calcium donors, is employed for combined osteomyelitis therapy. CaH2 reacts with water to sufficiently generate a strong alkali environment with hydroxide anions (OH-) to inhibit bacterial proliferation and induce bacterial death. The released calcium ions (Ca2+) induce calcium overload to kill bacteria first and then serves as calcium source to promote new bone formation. Another byproduct, hydrogen enhances the bacterial membrane permeability and scavenges excess reactive oxygen species (ROS). After incubation with bacteria, CaH2 significantly increases the permeability of the bacterial membrane, therefore increasing the entry of OH- and Ca2+ into bacterial cells, thereby leading to significant bacterial death. After being applied to S. aureus-infected mouse tibia osteomyelitis, CaH2 materials efficiently kill bacteria, relieve local inflammation, and promote new bone formation in a short time. Overall, bioactive metal hydride-associated "triple" hydrogen/alkaline/calcium therapy provides a new idea for the treatment of deep-site bacterial infection, which is beneficial for relieving the pressure caused by antibiotic-resistant bacteria.

Currently, methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis is a clinically life-threatening disease, however, long-term antibiotic treatment can lead to bacterial resistance, posing a huge challenge to treatment and public health. In this study, glucose-derived carbon spheres loaded with zinc oxide (ZnO@HTCS) are successfully constructed. This composite demonstrates the robust ability to generate reactive oxygen species (ROS) under ultrasound (US) irradiation, eradicating 99.788% ± 0.087% of MRSA within 15 min and effectively treating MRSA-induced osteomyelitis infection. Piezoelectric force microscopy tests and finite element method simulations reveal that the ZnO@HTCS composite exhibits superior piezoelectric catalytic performance compared to pure ZnO, making it a unique piezoelectric sonosensitizer. Density functional theory calculations reveal that the formation of a Mott-Schottky heterojunction and an internal piezoelectric field within the interface accelerates the electron transfer and the separation of electron-hole pairs. Concurrently, surface vacancies of the composite enable the adsorption of a greater amount of oxygen, enhancing the piezoelectric catalytic effect and generating a substantial quantity of ROS. This work not only presents a promising approach for augmenting piezoelectric catalysis through construction of a Schottky heterojunction interface but also provides a novel, efficient therapeutic strategy for treating osteomyelitis.

Antibiotic-resistant pathogens have become a global public health crisis, especially biofilm-induced refractory infections. Efficient, safe, and biofilm microenvironment (BME)-adaptive therapeutic strategies are urgently demanded to combat antibiotic-resistant biofilms. Here, inspired by the fascinating biological structures and functions of phages, the de novo design of a spiky Ir@Co3O4 particle is proposed to serve as an artificial phage for synergistically eradicating antibiotic-resistant Staphylococcus aureus biofilms. Benefiting from the abundant nanospikes and highly active Ir sites, the synthesized artificial phage can simultaneously achieve efficient biofilm accumulation, extracellular polymeric substance (EPS) penetration, and superior BME-adaptive reactive oxygen species (ROS) generation, thus facilitating the in situ ROS delivery and enhancing the biofilm eradication. Moreover, metabolomics found that the artificial phage obstructs the bacterial attachment to EPS, disrupts the maintenance of the BME, and fosters the dispersion and eradication of biofilms by down-regulating the associated genes for the biosynthesis and preservation of both intra- and extracellular environments. The in vivo results demonstrate that the artificial phage can treat the biofilm-induced recalcitrant infected wounds equivalent to vancomycin. It is suggested that the design of this spiky artificial phage with synergistic "penetrate and eradicate" capability to treat antibiotic-resistant biofilms offers a new pathway for bionic and nonantibiotic disinfection.

The emergence of antimicrobial-resistant bacterial infections poses a significant threat to public health, necessitating the development of innovative and effective alternatives to antibiotics. Photodynamic therapy (PDT) and immunotherapy show promise in combating bacteria. However, PDT's effectiveness is hindered by its low specificity to bacteria, while immunotherapy struggles to eliminate bacteria in immunosuppressive environments. In this work, we introduce an innovative near-infrared antimicrobial nanoplatform (ZFC) driven by bacterial metabolism. ZFC, comprising d-cysteine-functionalized pentafluorophenyl bacteriochlorin (FBC-Cy) coordinated with Zn2+, is designed for antimicrobial photodynamic-immune therapy (aPIT) against systemic bacterial infections. By specifically targeting bacteria via d-amino acid incorporation into bacterial surface peptidoglycans during metabolism, ZFC achieves precise bacterial clearance in wound and pulmonary infections, exhibiting an antimicrobial efficacy of up to 90 % with minimal damage to normal cells under 750 nm light. Additionally, ZFC enhances the activation of antigen-presenting cells by 3.2-fold compared to control groups. Furthermore, aPIT induced by ZFC triggers systemic immune responses and establishes immune memory, resulting in a 1.84-fold increase in antibody expression against bacterial infections throughout the body of mice. In conclusion, aPIT prompted by ZFC presents a approach to treating bacterial infections, offering a broad-spectrum solution for systemic bacterial infections. STATEMENT OF SIGNIFICANCE: The new concept demonstrated focuses on an innovative near-infrared antimicrobial nanoplatform (ZFC) for antimicrobial photodynamic-immune therapy (aPIT), highlighting its reliance on bacterial metabolism and its non-damaging effect on normal tissues. ZFC efficiently targets deep-tissue bacterial infections by harnessing bacterial metabolism, thereby enhancing therapeutic efficacy while sparing normal tissues from harm. This approach not only clears bacterial infections effectively but also induces potent adaptive immune responses, leading to the eradication of distant bacterial infections. By emphasizing ZFC's unique mechanism driven by bacterial metabolism and its tissue-sparing properties, this work underscores the potential for groundbreaking advancements in antimicrobial therapy. Such advancements hold promise for minimizing collateral damage to healthy tissues, thereby improving treatment outcomes and mitigating the threat of antimicrobial resistance. This integrated approach represents a significant progress forward in the development of next-generation antimicrobial therapies with enhanced precision and efficacy.

Micro/nanorobots (MNRs) are envisioned to provide revolutionary changes to therapies for infectious diseases as they can deliver various antibacterial agents or energies to many hard-to-reach infection sites. However, existing MNRs face substantial challenges in addressing complex infections that progress from superficial to deep tissues. Here, we develop swarming magnetic Fe3O4@polydopamine-tannic acid nanorobots (Fe3O4@PDA-TA NRs) capable of performing targeted bacteria elimination in complicated bacterial infections by integrating superficial photothermal and deep chemical strategies. The Fe3O4@PDA-TA nanoparticles (NPs), serving as building blocks of the nanorobots, are fabricated by in situ polymerization of dopamine followed by TA adhesion. When driven by alternating magnetic fields, Fe3O4@PDA-TA NPs can assemble into large energetic microswarms continuously flowing forward with tunable velocity. Thus, the swarming Fe3O4@PDA-TA NRs can be navigated to achieve rapid broad coverage of a targeted superficial area from a distance and rapidly eradicate bacteria residing there upon exposure to near-infrared (NIR) light due to their efficient photothermal conversion. Additionally, they can concentrate at deep infection sites by traversing through confined, narrow, and tortuous passages, exerting sustained antibacterial action through their surface TA-induced easy cell adhesion and subsequent membrane destruction. Therefore, the swarming Fe3O4@PDA-TA NRs show great potential for addressing complex superficial-to-deep infections. This study may inspire the development of future therapeutic microsystems for various diseases with multifunction synergies, task flexibility, and high efficiency.

Traditional external field-assisted therapies, e.g., microwave (MW) therapy and phototherapy, cannot effectively and minimally damage eliminate deep-seated infection, owing to the poor penetrability of light and low reactive oxygen species (ROS) stimulation capability of MW. Herein, an implantable and wireless-powered therapeutic platform (CNT-FeTHQ-TS), in which external MW can be converted into internal light via MW wireless-powered light-emitting chips, is designed to eradicate deep-seated tissue infections by MW-induced deep-seated photodynamic therapy. In application, CNT-FeTHQ-TS is implanted at internal lesions, and the chip emits light under external MW irradiation. Subsequently, CNT-FeTHQ coating in the platform can respond to both MW and light simultaneously to generate ROS and MW-hyperthermia for rapid and precise sterilization at focus. Importantly, MW also improves the photodynamic performance of CNT-FeTHQ by introducing vacancies in FeTHQ to facilitate the photoexcitation process and changing the spin state of electrons to inhibit the complexation of photogenerated electron-hole pairs, which were confirmed by simulation calculations and in situ MW-irradiated photoluminescence experiments. In vivo, CNT-FeTHQ-TS can effectively cure mice with Staphylococcus aureus infection in dorsal subcutaneous tissue. This work overcomes the key clinical limitations of safe energy transmission and conversion for treating deep-seated infections.

Antibiotics are frequently used to clinically treat osteomyelitis caused by bacterial infections. However, extended antibiotic use may result in drug resistance, which can be life threatening. Here, a heterojunction comprising Fe2O3/Fe3S4 magnetic composite is constructed to achieve short-term and efficient treat osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA). The Fe2O3/Fe3S4 composite exhibits powerful microwave (MW) absorption properties, thereby effectively converting incident electromagnetic energy into thermal energy. Density functional theory calculations demonstrate that Fe2O3/Fe3S4 possesses significant charge accumulation and oxygen-fixing capacity at the heterogeneous interface, which provides more active sites and oxygen sources for trapping electromagnetic hotspots. The finite element analysis indicates that Fe2O3/Fe3S4 displays a larger electromagnetism field enhancement parameter than Fe2O3 owing to a significant increase in electromagnetic hotspots. These hotspots contribute to charge differential accumulation and depletion motions at the interface, thereby augmenting the release of free electrons that subsequently combine with the oxygen adsorbed by Fe2O3/Fe3S4 to generate reactive oxygen species (ROS) and heat. This research, which achieves extraordinary bacterial eradication through the synergistic effect of microwave thermal therapy (MWTT) and microwave dynamic therapy (MDT), presents a novel strategy for treating deep-tissue bacterial infections.

Implant-related secondary infections are a challenging clinical problem. Sonodynamic therapy (SDT) strategies are promising for secondary biofilm infections by nonsurgical therapy. However, the inefficiency of SDT in existing acoustic sensitization systems limits its application. Therefore, we take inspiration from popular metamaterials and propose the design idea of a metainterface heterostructure to improve SDT efficiency. The metainterfacial heterostructure is defined as a periodic arrangement of heterointerface monoclonal cells that amplify the intrinsic properties of the heterointerface. Herein, we develop a TiO2/Ti2O3/vertical graphene metainterface heterostructure film on titanium implants. This metainterface heterostructure exhibits extraordinary sonodynamic and acoustic-to-thermal conversion effects under low-intensity ultrasound. The modulation mechanisms of the metainterface for electron accumulation and separation are revealed. The synergistic sonodynamic/mild sonothermal therapy disrupts biofilm infections (antibacterial rates: 99.99% for Staphylococcus aureus, 99.54% for Escherichia coli), and the osseointegration ability of implants is significantly improved in in vivo tests. Such a metainterface heterostructure film lays the foundation for the metainterface of manipulating electron transport to enhance the catalytic performance and holding promise for addressing secondary biofilm infections.

Bone infections caused by Staphylococcus aureus may lead to an inflammatory condition called osteomyelitis, which results in progressive bone loss. Biofilm formation, intracellular survival, and the ability of S. aureus to evade the immune response result in recurrent and persistent infections that present significant challenges in treating osteomyelitis. Moreover, people with diabetes are prone to osteomyelitis due to their compromised immune system, and in life-threatening cases, this may lead to amputation of the affected limbs. In most cases, bone infections are localized; thus, early detection and targeted therapy may prove fruitful in treating S. aureus-related bone infections and preventing the spread of the infection. Specific S. aureus components or overexpressed tissue biomarkers in bone infections could be targeted to deliver active therapeutics, thereby reducing drug dosage and systemic toxicity. Compounds like peptides and antibodies can specifically bind to S. aureus or overexpressed disease markers and combining these with therapeutics or imaging agents can facilitate targeted delivery to the site of infection. The effectiveness of photodynamic therapy and hyperthermia therapy can be increased by the addition of targeting molecules to these therapies enabling site-specific therapy delivery. Strategies like host-directed therapy focus on modulating the host immune mechanisms or signaling pathways utilized by S. aureus for therapeutic efficacy. Targeted therapeutic strategies in conjunction with standard surgical care could be potential treatment strategies for S. aureus-associated osteomyelitis to overcome antibiotic resistance and disease recurrence. This review paper presents information about the targeting strategies and agents for the therapy and diagnostic imaging of S. aureus bone infections.

To reduce food-borne bacterial infection caused by food spoilage, developing highly efficient food packing film is still an urgent need for food preservation. Herein, microwave-assisted antibacterial nanocomposite films CaO2@PVP/EA/CMC-Na (CP/EC) were synthesized using waste eggshell as precursor, egg albumen (EA) and sodium carboxymethylcellulose (CMCNa) as matrix by casting method. The size of CaO2@PVP (CP) nanoparticles with monodisperse spherical structures was 100-240 nm. When microwave and CP nanoparticles (0.05 mg/mL) were treated for 5 min, the mortality of E. coli and S. aureus could reach >97 %. Under microwave irradiation (6 min), the bactericidal rate of 2.5 % CP/EC film against E. coli and S. aureus reached 98.6 % and 97.2 %, respectively. After adding CP nanoparticles, the highest tensile strength (TS) and elongation at break (EB) of CP/EC film reached 19.59 MPa and 583.43 %, respectively. At 18 °C, the proliferation of bacterial colonies on meat can be significantly inhibited by 2.5 % CP/EC film. Detailed characterization showed that the excellent meat preservation activity was due to the synergistic effect of dynamic effect generated by ROS and thermal effect of microwave. This study provides a promising approach for the packaging application of polysaccharide- and protein-based biomass nanocomposite antibacterial edible films.

Vascularization and inflammation management are essential for successful bone regeneration during the healing process of large bone defects assisted by artificial implants/fillers. Therefore, this study is devoted to the optimization of the osteogenic microenvironment for accelerated bone healing through rapid neovascularization and appropriate inflammation inhibition that were achieved by applying a tantalum oxide (TaO)-based nanoplatform carrying functional substances at the bone defect. Specifically, TaO mesoporous nanospheres were first constructed and then modified by functionalized metal ions (Mg2+) with the following deferoxamine (DFO) loading to obtain the final product simplified as DFO-Mg-TaO. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed that the product was homogeneously dispersed hollow nanospheres with large specific surface areas and mesoporous shells suitable for loading Mg2+ and DFO. The biological assessments indicated that DFO-Mg-TaO could enhance the adhesion, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The DFO released from DFO-Mg-TaO promoted angiogenetic activity by upregulating the expressions of hypoxia-inducible factor-1 (HIF-1α) and vascular endothelial growth factor (VEGF). Notably, DFO-Mg-TaO also displayed anti-inflammatory activity by reducing the expressions of pro-inflammatory factors, benefiting from the release of bioactive Mg2+. In vivo experiments demonstrated that DFO-Mg-TaO integrated with vascular regenerative, anti-inflammatory, and osteogenic activities significantly accelerated the reconstruction of bone defects. Our findings suggest that the optimized DFO-Mg-TaO nanospheres are promising as multifunctional fillers to speed up the bone healing process.