Temperature-Activated Near-Infrared-II Fluorescence and SERS Dynamic-Reversible Probes for Long-Term Assessment of Osteoarthritis In Vivo.

The abnormal fluctuation of temperature in vivo usually reflects the progression of inflammatory diseases. Noninvasive, real-time, and accurate monitoring and imaging of temperature variation in vivo is advantageous for guiding the early diagnosis and treatment of disease, but it remains difficult to achieve. Herein, we developed a temperature-activated near-infrared-II fluorescence (NIR-II FL) and surface-enhanced Raman scattering (SERS) nanoprobe for long-term monitoring of temperature changes in rat arthritis and timely assessment of the status of osteoarthritis. The thermosensitive polymer bearing NIR-II FL dye was grafted onto the surface of nanoporous core-satellite gold nanostructures to form the nanoprobe, wherein the nanoprobe contains NIR-II FL and Raman reference signals that are independent of temperature change. The ratiometric FL1150/FL1550 and S1528/S2226 values of the nanoprobe exhibited a reversible conversion with temperature changes. The nanoprobe accurately distinguishes the temperature variations in the inflamed joint versus the normal joint in vivo by ratiometric FL and SERS imaging, allowing for an accurate diagnosis of inflammation. Meanwhile, it can continuously monitor fluctuations in temperature over an extended period during the onset and treatment of inflammation. The tested temperature change trend could be used as an indicator for early diagnosis of inflammation and real-time evaluation of therapeutic effects.

Applications of metals and metal compounds in improving the sensitivity of microfluidic biosensors - a review.

The enhancement of detection sensitivity in microfluidic sensors has been a continuously explored field. Initially, many strategies for sensitivity improvement involved introducing enzyme cascade reactions, but enzyme-based reactions posed challenges in terms of cost, stability, and storage. Therefore, there is an urgent need to explore enzyme-free cascade amplification methods, which are crucial for expanding the application range and improving detection stability. Metal or metal compound nanomaterials have gained great attention in the exploitation of microfluidic sensors due to their ease of preparation, storage, and lower cost. The unique physical properties of metallic nanomaterials, including surface plasmon resonance, surface-enhanced Raman scattering, metal-enhanced fluorescence, and surface-enhanced infrared absorption, contribute significantly to enhancing detection capabilities. The metal-based catalytic nanomaterials, exemplified by Fe3O4 nanoparticles and metal-organic frameworks, are considered viable alternatives to biological enzymes due to their excellent performance. Herein, we provide a detailed overview of the applications of metals and metal compounds in improving the sensitivity of microfluidic biosensors. This review not only highlights the current developments but also critically analyzes the challenges encountered in this field. Furthermore, it outlines potential directions for future research, contributing to the ongoing development of microfluidic biosensors with improved detection sensitivity.

X-ray Activated Nanoprodrug for Visualization of Cortical Microvascular Alterations and NIR-II Image-Guided Chemo-Radiotherapy of Glioblastoma.

The permeability of the highly selective blood-brain barrier (BBB) to anticancer drugs and the difficulties in defining deep tumor boundaries often reduce the effectiveness of glioma treatment. Thus, exploring the combination of multiple treatment modalities under the guidance of second-generation near-infrared (NIR-II) window fluorescence (FL) imaging is considered a strategic approach in glioma theranostics. Herein, a hybrid X-ray-activated nanoprodrug was developed to precisely visualize the structural features of glioma microvasculature and delineate the boundary of glioma for synergistic chemo-radiotherapy. The nanoprodrug comprised down-converted nanoparticle (DCNP) coated with X-ray sensitive poly(Se-Se/DOX-co-acrylic acid) and targeted Angiopep-2 peptide (DCNP@P(Se-DOX)@ANG). Because of its ultrasmall size and the presence of DOX, the nanoprodrug could easily cross BBB to precisely monitor and localize glioblastoma via intracranial NIR-II FL imaging and synergistically administer antiglioblastoma chemo-radiotherapy through specific X-ray-induced DOX release and radiosensitization. This study provides a novel and effective strategy for glioblastoma imaging and chemo-radiotherapy.

Advances in Injectable Hydrogels Based on Diverse Gelation Methods for Biomedical Imaging.

The injectable hydrogels can deliver the loads directly to the predetermined sites and form reservoirs to increase the enrichment and retention of the loads in the target areas. The preparation and injection of injectable hydrogels involve the sol-gel transformation of hydrogels, which is affected by factors such as temperature, ions, enzymes, light, mechanics (self-healing property), and pH. However, tracing the injection, degradation, and drug release from hydrogels based on different ways of gelation is a major concern. To solve this problem, contrast agents are introduced into injectable hydrogels, enabling the hydrogels to be imaged under techniques such as fluorescence imaging, photoacoustic imaging, magnetic resonance imaging, and radionuclide imaging. This review details methods for causing the gelation of imageable hydrogels; discusses the application of injectable hydrogels containing contrast agents in various imaging techniques, and finally explores the potential and challenges of imageable hydrogels based on different modes of gelation.

Bionic Bilayer Scaffold for Synchronous Hyperthermia Therapy of Orthotopic Osteosarcoma and Osteochondral Regeneration.

Large osseous void, postsurgical neoplastic recurrence, and slow bone-cartilage repair rate raise an imperative need to develop functional scaffold in clinical osteosarcoma treatment. Herein, a bionic bilayer scaffold constituting croconaine dye-polyethylene glycol@sodium alginate hydrogel and poly(l-lactide)/hydroxyapatite polymer matrix is fabricated to simultaneously achieve a highly efficient killing of osteosarcoma and an accelerated osteochondral regeneration. First, biomimetic osteochondral structure along with adequate interfacial interaction of the bilayer scaffold provide a structural reinforcement for transverse osseointegration and osteochondral regeneration, as evidenced by upregulated specific expressions of collagen type-I, osteopontin, and runt-related transcription factor 2. Meanwhile, thermal ablation of the synthesized nanoparticles and mitochondrial dysfunction caused by continuously released hydroxyapatite induce residual tumor necrosis synergistically. To validate the capabilities of inhibiting tumor growth and promoting osteochondral regeneration of our proposed scaffold, a novel orthotopic osteosarcoma model simulating clinical treatment scenarios of bone tumors is established on rats. Based on amounts of in vitro and in vivo results, an effective killing of osteosarcoma and a suitable osteal-microenvironment modulation of such bionic bilayer composite scaffold are achieved, which provides insightful implications for photonic hyperthermia therapy against osteosarcoma and following osseous tissue regeneration.

Ultrasound Activated Nanobowls with Deep Penetration for Enhancing Sonodynamic Therapy of Orthotopic Liver Cancer.

Owing to the high penetration ability and the safety of ultrasound (US) of sonodynamic therapy (SDT), it has gained significant attention in tumor treatment. However, its therapeutic efficiency depends on the performance of the sonosensitizers. The hypoxic microenvironment and abnormal stromal matrix restrict the full potential of sonosensitizers. In this study, a US-activated bowl-shaped nanobomb (APBN) is designed as a novel sonosensitizer to enhance the SDT effect through various means. This enhancement strategy combines three major characteristics: relieving tumor hypoxia, amplifying bubble cavitation damage, and US-movement-enhanced permeation. The unique bowl-shaped structure of APBN provides more favorable attachment sites for the generated oxygen gas bubbles. Thus, when catalase-like APBN catalyzes endogenous hydrogen peroxide to produce oxygen, bubbles accumulate at the groove, preventing the dissipation of oxygen and increasing the number of cavitation nuclei to improve the acoustic cavitation effect. This approach differs from traditional SDT strategies because it couples the sonodynamic effect with reactive oxygen species generation and bubble cavitation damage rather than a single action. Additionally, the asymmetric bowl-shaped structure generates a driving force under the US field, improving the distribution of sonosensitizers in the tumors. Using US and photoacoustic imaging for dual localization, these sonosensitizers can improve the accuracy of orthotopic liver tumor treatment, which presents a promising avenue for the treatment of deep tumors.

Activatable Probes for Ratiometric Imaging of Endogenous Biomarkers In Vivo.

Dynamic variations in the concentration and abnormal distribution of endogenous biomarkers are strongly associated with multiple physiological and pathological states. Therefore, it is crucial to design imaging systems capable of real-time detection of dynamic changes in biomarkers for the accurate diagnosis and effective treatment of diseases. Recently, ratiometric imaging has emerged as a widely used technique for sensing and imaging of biomarkers due to its advantage of circumventing the limitations inherent to conventional intensity-dependent signal readout methods while also providing built-in self-calibration for signal correction. Here, the recent progress of ratiometric probes and their applications in sensing and imaging of biomarkers are outlined. Ratiometric probes are classified according to their imaging mechanisms, and ratiometric photoacoustic imaging, ratiometric optical imaging including photoluminescence imaging and self-luminescence imaging, ratiometric magnetic resonance imaging, and dual-modal ratiometric imaging are discussed. The applications of ratiometric probes in the sensing and imaging of biomarkers such as pH, reactive oxygen species (ROS), reactive nitrogen species (RNS), glutathione (GSH), gas molecules, enzymes, metal ions, and hypoxia are discussed in detail. Additionally, this Review presents an overview of challenges faced in this field along with future research directions.

STING Agonist-Loaded Nanoparticles Promotes Positive Regulation of Type I Interferon-Dependent Radioimmunotherapy in Rectal Cancer.

Hypoxia-associated radioresistance in rectal cancer (RC) has severely hampered the response to radioimmunotherapy (iRT), necessitating innovative strategies to enhance RC radiosensitivity and improve iRT efficacy. Here, a catalytic radiosensitizer, DMPtNPS, and a STING agonist, cGAMP, are integrated to overcome RC radioresistance and enhance iRT. DMPtNPS promotes efficient X-ray energy transfer to generate reactive oxygen species, while alleviating hypoxia within tumors, thereby increasing radiosensitivity. Mechanistically, the transcriptomic and immunoassay analysis reveal that the combination of DMPtNPS and RT provokes bidirectional regulatory effects on the immune response, which may potentially reduce the antitumor efficacy. To mitigate this, cGAMP is loaded into DMPtNPS to reverse the negative impact of DMPtNPS and RT on the tumor immune microenvironment (TiME) through the type I interferon-dependent pathway, which promotes cancer immunotherapy. In a bilateral tumor model, the combination treatment of RT, DMPtNPS@cGAMP, and αPD-1 demonstrates a durable complete response at the primary site and enhanced abscopal effect at the distant site. This study highlights the critical role of incorporating catalytic radiosensitizers and STING agonists into the iRT approach for RC.

Imaging-Guided Antibacterial Based on Gold Nanocrystals and Assemblies.

Bacterial infection becomes a severe threat to human life and health worldwide. Antibiotics with the ability to resist pathogenic bacteria are therefore widely used, but the misuse or abuse of antibiotics can generate multidrug-resistant bacteria or resistant biofilms. Advanced antibacterial technologies are needed to counter the rapid emergence of drug-resistant bacteria. With the excellent optical properties, engineerable surface chemistry, neglectable biotoxicity, gold nanocrystals are particularly attractive in biomedicine for cancer therapy and antibacterial therapy, as well as nanoprobes for bioimaging and disease diagnosis. In this perspective, gold nanocrystal-based antibacterial performance and deep-tissue imaging are summarized, including near-infrared-light excited photoacoustic imaging and fluorescence imaging through deep tissue infections. On the basis of integrating "imaging-therapy-targeting" in single nanotheranostic, the current challenges of imaging-guided antibacterial and therapy based on gold nanocrystals are discussed, and some insights are provided into the gold nanocrystal-based nanoplatform that integrates antibacterial activity and therapy. This perspective is expected to provide comprehensive guidance for diagnosing and combating bacterial infections based on gold nanostructures.

Systemic therapy with or without local intervention for oligometastatic oesophageal squamous cell carcinoma (ESO-Shanghai 13): an open-label, randomised, phase 2 trial.

BACKGROUND: The efficacy of local therapy for patients with oligometastatic oesophageal squamous cell carcinoma is unclear. We aimed to assess the efficacy of local plus systemic therapy compared with systemic therapy alone in patients with oligometastatic oesophageal squamous cell carcinoma. METHODS: The ESO-Shanghai 13 trial was a randomised, open-label, multicentre, phase 2 trial. Patients (aged ≥18 years) were recruited from six hospitals in China with histological confirmation of oligometastatic oesophageal squamous cell carcinoma with a controlled primary tumour and one to four metastatic lesions. Eligible patients were randomly assigned via a computer-generated schedule in a 1:1 ratio to receive either systemic therapy alone (ie, systemic therapy only group) or combined systemic and local therapy (ie, systemic and local therapy group). The systemic therapy regimens in both groups were at the discretion of the investigator and included chemotherapy alone, anti-PD-1 antibodies alone, or chemotherapy plus anti-PD-1 antibodies. Local therapy-radiotherapy, surgery, or thermal ablation-was delivered to all metastatic lesions for patients in the systemic and local therapy group. Randomisation was balanced dynamically on three factors: the number of disease sites, the lines of systemic therapy, and the location of the metastases. Patients and investigators were not masked to treatment allocation. The primary endpoint was progression-free survival, defined as the time from randomisation to progression or death from any cause in the intention-to-treat population. The safety population included all patients who had undergone random assignment and at least one of the intended therapies. This trial is registered with ClinicalTrials.gov, NCT03904927. The trial is ongoing but closed to new participants. FINDINGS: 116 patients were screened for enrolment between March 5, 2019, and Sept 16, 2021, and 104 patients who met the eligibility criteria were randomly assigned to the systemic and local therapy group (n=53) or the systemic therapy only group (n=51). 20 (38%) patients in the systemic plus local therapy group and 23 (45%) patients in the systemic therapy only group received anti-PD-1 antibody-based systemic therapy; three patients in the systemic and local therapy group did not receive systemic therapy. At a median follow-up of 30·5 months (IQR 24·7-37·8), median progression-free survival was 15·3 months (95% CI 10·1-20·5) in the systemic and local therapy group versus 6·4 months (5·2-7·6) in the systemic therapy only group (stratified hazard ratio 0·26 [95% CI 0·16-0·42]; stratified log rank p<0·0001). Grade 1-2 acute oesophagitis was more common in the systemic and local therapy group than in the systemic therapy only group (10 [19%] vs one [2%] patients; p=0·036). The number of patients who had grade 3 or worse treatment-related adverse events was similar between groups (25 [47%] vs 21 [41%]; p=0·538), with the most common adverse events being leukocytopenia (17 [32%] vs 18 [35%]) and neutropenia (19 [36%] vs 20 [39%]). Treatment-related deaths occurred in two patients in the systemic and local therapy group and one patient in the systemic therapy only group. INTERPRETATION: The addition of local treatment for metastases could significantly improve progression-free survival among patients with oligometastatic oesophageal squamous cell carcinoma being treated with systemic therapy. Our findings suggest that combining local and systemic therapy could be a treatment option for patients with oligometastatic oesophageal squamous cell carcinoma, but further support from phase 3 trials is required. FUNDING: Science and Technology Commission of Shanghai Municipality, National Nature Science Foundation of China, and Shanghai Municipal Health Commission. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Ultrasound activated probe for disease imaging and therapy In-Vivo.

Sonodynamic therapy (SDT) is the use of ultrasound (US) to excite sonosensitizers to produce reactive oxygen species (ROS) to induce tumor cell death, thereby achieving therapeutic purposes. Based on the strong tissue penetration ability of ultrasound, SDT can realize the treatment of deeper tumors, and it is targeted, can be specifically concentrated at the tumor site, and has little impact on surrounding normal tissues. It has broad clinical transformation prospects. Therefore, sonosensitizers are the key to SDT, and the exploration of sonosensitizers with excellent therapeutic performance has received great attention. We reviewed the development of ultrasound-inspired sound sensitizers for imaging and treatment. First, different types of sonosensitizers are introduced, the construction and performance of inorganic, organic and hybrid types of sonosensitizers are evaluated, followed by a review of different image-guided SDT, and finally the key problems and solutions in this field are discussed in detail.

Difunctional Ag nanoparticles with high lithiophilic and conductive decorate on core-shell SiO2 nanospheres for dendrite-free lithium metal anodes.

Lithium metal is an attractive and promising anode material due to its high energy density and low working potential. However, the uncontrolled growth of lithium dendrites during repeated plating and stripping processes hinders the practical application of lithium metal batteries, leading to low Coulombic efficiency, poor lifespan, and safety concerns. In this study, we synthesized highly lithiophilic and conductive Ag nanoparticles decorated on SiO2 nanospheres to construct an optimized lithium host for promoting uniform Li deposition. The Ag nanoparticles not only act as lithiophilic sites but also provide high electrical conductivity to the Ag@SiO2@Ag anode. Additionally, the SiO2 layer serves as a lithiophilic nucleation agent, ensuring homogeneous lithium deposition and suppressing the growth of lithium dendrites. Theoretical calculations further confirm that the combination of Ag nanoparticles and SiO2 effectively enhances the adsorption ability of Ag@SiO2@Ag with Li+ ions compared to pure Ag and SiO2 materials. As a result, the Ag@SiO2@Ag coating, with its balanced lithiophilicity and conductivity, demonstrates excellent electrochemical performance, including high Coulombic efficiency, low polarization voltage, and long cycle life. In a full lithium metal cell with LiFePO4 cathode, the Ag@SiO2@Ag anode exhibits a high capacity of 133.1 and 121.4 mAh/g after 200 cycles at rates of 0.5 and 1C, respectively. These results highlight the synergistic coupling of lithiophilicity and conductivity in the Ag@SiO2@Ag coating, providing valuable insights into the field of lithiophilic chemistry and its potential for achieving high-performance batteries in the next generation.

Quantitative detection of microRNA-21 in vivo using in situ assembled photoacoustic and SERS nanoprobes.

Accurately quantifying microRNA levels in vivo is of great importance for cancer staging and prognosis. However, the low abundance of microRNAs and interference from the complex tumor microenvironment usually limit the real-time quantification of microRNAs in vivo. Herein, for the first time, we develop an ultrasensitive microRNA (miR)-21 activated ratiometric nanoprobe for quantification of the miR-21 concentration in vivo without signal amplification as well as dynamic tracking of its distribution. The core-satellite nanoprobe by miR-21 triggered in situ self-assembly was built on nanogapped gold nanoparticles (AuNNP probe) and gold nanoparticles (AuNP probe). The AuNP probe generated a photoacoustic (PA) signal and ratiometric SERS signal with the variation of miR-21, whereas the AuNNP probe served as an internal standard, enabling ratiometric SERS imaging of miR-21. The absolute concentration of miR-21 in MCF-7 tumor-bearing mice was quantified to be 83.8 ± 24.6 pM via PA and ratiometric SERS imaging. Our strategy provides a powerful approach for the quantitative detection of microRNAs in vivo, providing a reference for the clinical treatment of cancer.

Ratiometric Optical and Photoacoustic Imaging In Vivo in the Second Near-Infrared Window.

ConspectusOptical imaging and photoacoustic (PA) imaging have become essential tools to investigate physiological or pathological processes at the molecular level in vivo. The detection of variations at the molecular level in vivo is particularly important owing to the rapid progression of diseases. However, most studies have mainly focused on plain qualitative molecular imaging and detection, which is characterized by the absence of a reference signal in one-channel responsive imaging. To overcome the limitation and quantitatively detect molecules in situ, this Account reviews the recent contributions of our group to the quantitative imaging field in the form of ratiometric optical and PA imaging in vivo in the second near-infrared window (NIR-II, 950-1700 nm).In this Account, we present recent advances that our group has made in ratiometric imaging probe design and biomedical applications by constructing probes based on ratiometric optical imaging and ratiometric PA imaging. First, we highlight the design strategies of ratiometric optical probes that were based on organic ratiometric molecular probes, radio-activated organic ratiometric probes, and hybrid organic-inorganic assembled ratiometric probes. Subsequently, the design strategies of the ratiometric NIR-II optical nanoprobes with activated bioluminescence resonance energy transfer (BRET), Förster resonance energy transfer (FRET), and nonradiative energy transfer (NRET) effects provide a reliable tool to achieve the ratiometric detection of endogenous signaling molecules and thereby apply it to the monitoring and evaluation of the efficacy of photodynamic therapy, radiotherapy, and immunotherapy to guide the treatment process. In addition, we systematically introduce the functional design principles of ratiometric PA imaging probes based on core-shell nanoprobes, core-satellite nanoprobes, and universal hybrid nanoprobes, where we have established that reference signal and sensing signal can be obtained from the random assortment of plasmonic components and organic semiconducting molecules using a phase separation strategy. On these insights, we discuss the rational and detailed biomedical applications of ratiometric PA imaging probes which include accurate quantitative detection of disease-related molecules in inflammation or tumors in real time. In these champion implementations of ratiometric PA imaging probes, different diagnostic modules have been linked through compound modification with activation characteristics (e.g., pH, redox, enzyme, hypoxia). Finally, we present the challenges and perspectives for ratiometric probes based on optical imaging and PA imaging for multitarget design and future clinical translation. We believe that the upcoming generations of ratiometric imaging probes would have promising potential applications in the precise diagnosis of diseases. Finally, this Account may stimulate innovative studies in the design of ratiometric imaging probes and exploration of their clinical applications.

Self-Reporting Molecular Prodrug for In Situ Quantitative Sensing of Drug Release by Ratiometric Photoacoustic Imaging.

Understanding the pharmacokinetics of prodrugs in vivo necessitates quantitative, noninvasive, and real-time monitoring of drug release, despite its difficulty. Ratiometric photoacoustic (PA) imaging, a promising deep tissue imaging technology with a unique capacity for self-calibration, can aid in solving this problem. Here, for the first time, a methylamino-substituted Aza-BODIPY (BDP-N) and the chemotherapeutic drug camptothecin (CPT) are joined via a disulfide chain to produce the molecular theranostic prodrug (BSC) for real-time tumor mapping and quantitative visualization of intratumoral drug release using ratiometric PA imaging. Intact BSC has an extremely low toxicity, with a maximum absorption at ∼720 nm; however, endogenous glutathione (GSH), which is overexpressed in tumors, will cleave the disulfide bond and liberate CPT (with full toxicity) and BDP-N. This is accompanied by a significant redshift in absorption at ∼800 nm, resulting in the PA800/PA720 ratio. In vitro, a linear relationship is successfully established between PA800/PA720 values and CPT release rates, and subsequent experiments demonstrate that this relationship can also be applied to the quantitative detection of intratumoral CPT release in vivo. Notably, the novel ratiometric strategy eliminates nonresponsive interference and amplifies the multiples of the signal response to significantly improve the imaging contrast and detection precision. Therefore, this research offers a viable alternative for the design of molecular theranostic agents for the clinical diagnosis and treatment of tumors.

Combination of intercropping maize and soybean with root exudate additions reduces metal mobility in soil-plant system under wastewater irrigation.

The effects of root exudates and irrigation with treated wastewater on heavy metal mobility and soil bacterial composition under intercropping remain poorly understood. We conducted a pot experiment with maize and soybean grown in monocultures or intercultures, irrigated with either groundwater or treated wastewater. In addition, the pre-collected root exudates from hydroponic culture with mono- or inter-cropped maize and soybean were applied to the soil at four levels (0 %, 16 %, 32 % and 64 %). The results showed that application of root exudates increased plant growth and soil nutrient content. The analysis of "Technique for Order of Preference by Similarity to Ideal Solution" for higher plant biomass and lower soil Cd and Pb concentrations indicated that the best performance of soybean under treated wastewater irrigation was recorded under intercropping applied with 64 % of exudates, with a performance score of 0.926 and 0.953 for Cd and Pb, respectively. The second-best performance of maize under treated wastewater irrigation was also observed under intercropping applied with 64 % of exudates. Root exudate application reduced heavy metals migration in the soil-plant system, with a greater impact in intercropping than in monocropping. In addition, certain soil microorganisms were also increased with root exudate application, regardless of irrigation water. This study suggests that appropriate application of root exudates could potentially improve plant growth and soil health, and reduce toxic heavy metal concentrations in soils and plants irrigated with treated wastewater.

Molecular radio afterglow probes for cancer radiodynamic theranostics.

X-ray-induced afterglow and radiodynamic therapy tackle the tissue penetration issue of optical imaging and phototherapy. However, inorganic nanophosphors used in this therapy have their radio afterglow dynamic function as always on, limiting the detection specificity and treatment efficacy. Here we report organic luminophores (IDPAs) with near-infrared afterglow and 1O2 production after X-ray irradiation for cancer theranostics. The in vivo radio afterglow of IDPAs is >25.0 times brighter than reported inorganic nanophosphors, whereas the radiodynamic production of 1O2 is >5.7 times higher than commercially available radio sensitizers. The modular structure of IDPAs permits the development of a smart molecular probe that only triggers its radio afterglow dynamic function in the presence of a cancer biomarker. Thus, the probe enables the ultrasensitive detection of a diminutive tumour (0.64 mm) with superb contrast (tumour-to-background ratio of 234) and tumour-specific radiotherapy for brain tumour with molecular precision at low dosage. Our work reveals the molecular guidelines towards organic radio afterglow agents and highlights new opportunities for cancer radio theranostics.

Ultrasound-Activated NIR Chemiluminescence for Deep Tissue and Tumor Foci Imaging.

Fluorescence imaging requires real-time external light excitation; however, it has the drawbacks of autofluorescence and shallower penetration depth, limiting its application in deep tissue imaging. At the same time, ultrasound (US) has high spatiotemporal resolution, deep penetrability, noninvasiveness, and precise localization of lesions; thus, it can be a promising alternative to light. However, US-activated luminescence has been rarely reported. Herein, an US-activated near-infrared (NIR) chemiluminescence (CL) molecule, namely, PNCL, is designed by protoporphyrin IX as a sonosensitizer moiety and a phenoxy-dioxetane precursor containing a dicyanomethyl chromone acceptor scaffold (NCL) as the US-responsive moiety. After therapeutic US radiation (1 MHz), the singlet oxygen (1O2), as an "intermediary", oxidizes the enol-ether bond of the NCL moiety and then emits NIR light via spontaneous decomposition. Combining the deep penetrability of US with a high signal-to-background ratio of NIR CL, the designed probe PNCL successfully realizes US-activated deep tissue imaging (∼20 mm) and selectively turns on signals in specific tumor foci. Bridging US chemistry with luminescence using an "intermediary" will provide new imaging methods for accurate cancer diagnosis.

Atomically Site Synergistic Effects of Dual-Atom Nanozyme Enhances Peroxidase-like Properties.

Pursuing effective and generalized strategies for modulating the electronic structures of atomically dispersed nanozymes with remarkable catalytic performance is exceptionally attractive yet challenging. Herein, we developed a facile "formamide condensation and carbonization" strategy to fabricate a library of single-atom (M1-NC; 6 types) and dual-atom (M1/M2-NC; 13 types) metal-nitrogen-carbon nanozymes (M = Fe, Co, Ni, Mn, Ru, Cu) to reveal peroxidase- (POD-) like activities. The Fe1Co1-NC dual-atom nanozyme with Fe1-N4/Co1-N4 coordination displayed the highest POD-like activity. Density functional theory (DFT) calculations revealed that the Co atom site synergistically affects the d-band center position of the Fe atom site and served as the second reaction center, which contributes to better POD-like activity. Finally, Fe1Co1 NC was shown to be effective in inhibiting tumor growth both in vitro and in vivo, suggesting that diatomic synergy is an effective strategy for developing artificial nanozymes as novel nanocatalytic therapeutics.

Drug-Free Antimicrobial Nanomotor for Precise Treatment of Multidrug-Resistant Bacterial Infections.

Manufacturing heteronanostructures with specific physicochemical characteristics and tightly controllable designs is very appealing. Herein, we reported NIR-II light-driven dual plasmonic (AuNR-SiO2-Cu7S4) antimicrobial nanomotors with an intended Janus configuration through the overgrowth of copper-rich Cu7S4 nanocrystals at only one high-curvature site of Au nanorods (Au NRs). These nanomotors were applied for photoacoustic imaging (PAI)-guided synergistic photothermal and photocatalytic treatment of bacterial infections. Both the photothermal performance and photocatalytic activity of the nanomotors are dramatically improved owing to the strong plasmon coupling between Au NRs and the Cu7S4 component and enhanced energy transfer. The motion behavior of nanomotors promotes transdermal penetration and enhances the matter-bacteria interaction. More importantly, the directional navigation and synergistic antimicrobial activity of the nanomotors could be synchronously driven by NIR-II light. The marriage of active motion and enhanced antibacterial activity resulted in the expected good antibacterial effects in an abscess infection mouse model.