Ultrasound (US)-driven sonodynamic therapy (SDT) has demonstrated wide application prospects in the eradication of deep-seated bacterial infections due to its noninvasiveness, site-confined irradiation, and high-tissue-penetrating capability. However, the ineffective accumulation of sonosensitizers at the infection site, the hypoxic microenvironment, as well as rapid depletion of oxygen during SDT greatly hamper the therapeutic efficacy of SDT. Herein, an US-switchable nanozyme system was proposed for the controllable generation of catalytic oxygen and sonosensitizer-mediated reactive oxygen species during ultrasound activation, thereby alleviating the hypoxia-associated barrier and augmenting SDT efficacy. This nanoplatform (Pd@Pt-T790) was easily prepared by bridging enzyme-catalytic Pd@Pt nanoplates with the organic sonosensitizer meso-tetra­(4-carboxyphenyl)­porphine (T790). It was really interesting to find that the modification of T790 onto Pd@Pt could significantly block the catalase-like activity of Pd@Pt, whereas upon US irradiation, the nanozyme activity was effectively recovered to catalyze the decomposition of endogenous H2O2 into O2. Such “blocking and activating” enzyme activity was particularly important for decreasing the potential toxicity and side effects of nanozymes on normal tissues and has potential to realize active, controllable, and disease-loci-specific nanozyme catalytic behavior. Taking advantage of this US-switchable enzyme activity, outstanding accumulation in infection sites, as well as excellent biocompatibility, the Pd@Pt-T790-based SDT nanosystem was successfully applied to eradicate methicillin-resistant Staphylococcus aureus (MRSA)-induced myositis, and the sonodynamic therapeutic progression was noninvasively monitored by photoacoustic imaging and magnetic resonance imaging. The developed US-switchable nanoenzyme system provides a promising strategy for augmenting sonodynamic eradication of deep-seated bacterial infection actively, controllably, and precisely.

Rapid emergence of multidrug resistant (MDR) "superbugs" poses a severe threat to global health. Notably, undeveloped diagnosis and concomitant treatment failure remain highly challenging. Herein, we report a sonotheranostic strategy to achieve bacteria-specific labeling and visualized sonodynamic therapy (SDT). Using maltohexaose-decorated cholesterol and bacteria-responsive lipid compositions, a smart nanoliposomes platform (MLP18) was developed for precise delivery of purpurin 18, a potent sonosensitizer proved in this study. Taking advantage of the bacteria-specific maltodextrin transport pathway, the prepared MLP18 can specifically target the bacterial infection site and accurately distinguish the foci from sterile inflammation or cancer with a highly selective fluorescence/photoacoustic signal on the bacteria-infected site of mice. Moreover, the bacteria-responsive feature of MLP18 activated an efficient release and internalization of high concentration sonosensitizer into bacterial cells, resulting in effective sonodynamic elimination of MDR bacteria. In situ MRI monitoring visualized such potent sonodynamic activity and indicated that MLP18-mediated SDT could successfully eradicate inflammation and abscess from mice with bacterial myositis. In view of the above advantages, the developed nanoliposomes may serve as a promising sonotheranostic platform against MDR bacteria in the areas of healthcare.

Micro/nanorobots have been extensively explored as a tetherless small-scale robotic biodevice to perform minimally invasive interventions in hard-to-reach regions. Despite the emergence of versatile micro/nanorobots in recent years, matched in vivo development remains challenging, limited by unsatisfactory integration of core functions. Herein, we report a polydopamine (PDA)-coated magnetic microswimmer consisting of a magnetized Spirulina (MSP) matrix and PDA surface. Apart from the properties of the existing MSP (e.g., robust propulsion, natural fluorescence, tailored biodegradation, and selective cytotoxicity), the introduced PDA coating enhances the photoacoustic (PA) signal and photothermal effect of the MSP, thus making PA image tracking and photothermal therapy possible. Meanwhile, the PDA’s innate fluorescence quenching and diverse surface reactivity allows an off–on fluorescence diagnosis with fluorescence probes (e.g., coumarin 7). As a proof of concept, real-time image tracking (by PA imaging) and desired theranostic capabilities of PDA-MSP microswimmer swarms are demonstrated for the treatment of pathogenic bacterial infection. Our study suggests a feasible antibacterial microrobot for in vivo development and a facile yet versatile functionalization strategy of micro/nanorobots.

Antibiotic‐free methods hold particular promise for preventing and controlling multidrug‐resistant (MDR) bacterial infection via eradiation of bacteria and their pathogenic virulence. A facile and bioinspired strategy is presented for bridging antibacterial sonodynamic therapy and antivirulence immunotherapy. As a proof‐of‐concept, an antibody which neutralizes alpha‐toxin of methicillin‐resistant Staphylococcus aureus (MRSA) is genetically engineered on to the surface of cell membrane nanovesicles, which then undergo sonosensitizer encapsulation. Compared with conventional passive virulence absorption using natural red blood membrane, the highly active antibody–toxin interaction enables the nanovesicles to capture virulence more potently in vitro. Upon ultrasound activation, the sonosensitizers efficiently generate reactive oxygen species to kill bacteria and accelerate the virulence clearance. In vivo optical imaging shows that the antibody‐piloted nanocapturer can successfully locate MRSA infection and accurately distinguish the foci from sterile inflammation. In situ magnetic resonance imaging and oxyhemoglobin saturation detection visualize the treatment progression, revealing a complete sono‐immunotherapeutic eradication of MRSA myositis in mice. The first combination of antibacterial sonodynamic therapy and antivirulence immunotherapy, which promises a new way for antibiotic‐free nanotheranostics to robustly combat MDR bacterial infections, is presented.

Soil gross nitrogen (N) mineralization (GNM), a key microbial process in the global N cycle, is mainly controlled by climate and soil properties. This study provides for the first time a comprehensive analysis of the role of soil physicochemical properties and climate and their interactions with soil microbial biomass (MB) in controlling GNM globally. Through a meta‐analysis of 970 observations from 337 published papers from various ecosystems, we found that GNM was positively correlated with MB, total carbon, total N and precipitation, and negatively correlated with bulk density (BD) and soil pH. Our multivariate analysis and structural equation modeling revealed that GNM is driven by MB and dominantly influenced by BD and precipitation. The higher total N accelerates GNM via increasing MB. The decrease in BD stimulates GNM via increasing total N and MB, whereas higher precipitation stimulates GNM via increasing total N. Moreover, the GNM varies with ecosystem type, being greater in forests and grasslands with high total carbon and MB contents and low BD and pH compared to croplands. The highest GNM was observed in tropical wet soils that receive high precipitation, which increases the supply of soil substrate (total N) to microbes. Our findings suggest that anthropogenic activities that affect soil microbial population size, BD, soil substrate availability, or soil pH may interact with changes in precipitation regime and land use to influence GNM, which may ultimately affect ecosystem productivity and N loss to the environment.

Although ultrasound-based therapeutic strategies have achieved great success in the battle against antibiotic-resistant bacterial infections, various sonodynamic treatments still suffer from poor therapeutic efficiency, failing to completely eradicate infections. Thus, more potent strategies are urgently required. Herein, a novel ultrasound-driven treatment modality, sonoactivated chemodynamic therapy (SCDT), is proposed, which shows a robust generation of superoxide anion and destructive hydroxyl radical via sonotriggered catalytic reactions. This SCDT platform is prepared by grafting Fe 3+ onto polyethylenimine-modified bismuth oxybromide (BiOBr) nanoplates. During sonocatalysis, the introduction of Fe 3+ can effectively separate the holes (h +) and electrons (e-) of BiOBr NPs and shorten their transport path of valence electrons, resulting in the activation of multioxygen reduction and Fenton reaction to generate abundant reactive oxygen species against methicillin-resistant Staphylococcus aureus (MRSA) infection. More importantly, Fe 3+ can also serve as a magnetic resonance imaging (MRI) contrast agent to achieve the accurate diagnosis of bacterial infection. The SCDT-mediated bactericidal outcome can be monitored by in situ monitoring through MRI technique, revealing a complete elimination of MRSA myositis in mice. Collectively, its deep tissue penetration, high therapeutic efficacy, and noninvasive properties make SCDT a promising therapeutic modality for combating multidrug-resistant bacterial infection.

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To address the urgent need for effective sonodynamic therapy (SDT), a facile and efficient strategy is developed for fabricating a new class of sonotheranostics. Herein, a Fe(III)-porphyrin nano-sonosensitizer is prepared by a one-step coordination synthesis, and then anchored with Bis(DPA-Zn)-RGD and manganese superoxide dismutase (SOD2) siRNA. Benefiting from the delicate interactions of the Fe(III)-coordinated nanoformulations, a highly potent sono/gene combinational therapy guided by fluorescence/magnetic resonance imaging is achieved. Importantly, this sonotheranostics significantly enhances the SDT effect of porphyrin through the cancer-targeted delivery capability and enhanced reactive oxygen species production via triple-regulated approaches, including down-regulation of SOD2, depletion of glutathione, and generation of Fenton reaction. This work opens up new perspectives for developing versatile sonotheranostics to overcome the clinical challenges of SDT.