A Vacancy-Engineering Ferroelectric Nanomedicine for Cuproptosis/Apoptosis Co-Activated Immunotherapy.

Low efficacy of immunotherapy due to the poor immunogenicity of most tumors and their insufficient infiltration by immune cells highlights the importance of inducing immunogenic cell death and activating immune system for achieving better treatment outcomes. Herein, ferroelectric Bi2CuO4 nanoparticles with rich copper vacancies (named BCO-VCu) are rationally designed and engineered for ferroelectricity-enhanced apoptosis, cuproptosis, and the subsequently evoked immunotherapy. In this structure, the suppressed recombination of the electron-hole pairs by the vacancies and the band bending by the ferroelectric polarization lead to high catalytic activity, triggering reactive oxygen species bursts and inducing apoptosis. The cell fragments produced by apoptosis serve as antigens to activate T cells. Moreover, due to the generated charge by the ferroelectric catalysis, this nanomedicine can act as "a smart switch" to open the cell membrane, promote nanomaterial endocytosis, and shut down the Cu+ outflow pathway to evoke cuproptosis, and thus a strong immune response is triggered by the reduced content of adenosine triphosphate. Ribonucleic acid transcription tests reveal the pathways related to immune response activation. Thus, this study firstly demonstrates a feasible strategy for enhancing the efficacy of immunotherapy using single ferroelectric semiconductor-induced apoptosis and cuproptosis.

Revealing the Optimization Route of Piezoelectric Sonosensitizers: From Mechanism to Engineering Methods.

Piezoelectric catalysis is a novel catalytic technology that has developed rapidly in recent years and has attracted extensive interest among researchers in the field of tumor therapy for its acoustic-sensitizing properties. Nevertheless, researchers are still controversial about the key technical difficulties in the modulation of piezoelectric sonosensitizers for tumor therapy applications, which is undoubtedly a major obstacle to the performance modulation of piezoelectric sonosensitizers. Clarification of this challenge will be beneficial to the design and optimization of piezoelectric sonosensitizers in the future. Here, the authors start from the mechanism of piezoelectric catalysis and elaborate the mechanism and methods of defect engineering and phase engineering for the performance modulation of piezoelectric sonosensitizers based on the energy band theory. The combined therapeutic strategy of piezoelectric sonosensitizers with enzyme catalysis and immunotherapy is introduced. Finally, the challenges and prospects of piezoelectric sonosensitizers are highlighted. Hopefully, the explorations can guide researchers toward the optimization of piezoelectric sonosensitizers and can be applied in their own research.

Colorimetric and Photothermal Dual-Modal Switching Lateral Flow Immunoassay Based on a Forced Dispersion Prussian Blue Nanocomposite for the Sensitive Detection of Prostate-Specific Antigen.

Prostate-specific antigen (PSA) is a key marker for a prostate cancer diagnosis. The low sensitivity of traditional lateral flow immunoassay (LFIA) methods makes them unsuitable for point-of-care testing. Herein, we designed a nanozyme by in situ growth of Prussian blue (PB) within the pores of dendritic mesoporous silica (DMSN). The PB was forcibly dispersed into the pores of DMSN, leading to an increase in exposed active sites. Consequently, the atom utilization is enhanced, resulting in superior peroxidase (POD)-like activity compared to that of cubic PB. Antibody-modified DMSN@PB nanozymes serve as immunological probes in an enzymatic-enhanced colorimetric and photothermal dual-signal LFIA for PSA detection. After systematic optimization, the LFIA based on DMSN@PB successfully achieves a 4-fold amplification of the colorimetric signal within 7 min through catalytic oxidation of the chromogenic substrate by POD-like activity. Moreover, DMSN@PB exhibits an excellent photothermal conversion ability under 808 nm laser irradiation. Accordingly, photothermal signals are introduced to improve the anti-interference ability and sensitivity of LFIA, exhibiting a wide linear range (1-40 ng mL-1) and a low PSA detection limit (0.202 ng mL-1), which satisfies the early detection level of prostate cancer. This research provides a more accurate and reliable visualization analysis methodology for the early diagnosis of prostate cancer.

A Functional "Key" Amplified Piezoelectric Effect Modulates ROS Storm with an Open Source for Multimodal Synergistic Cancer Therapy.

Chemodynamic therapy (CDT) is a non-invasive strategy for generating reactive oxygen species (ROS) and is promising for cancer treatment. However, increasing ROS in tumor therapy remains challenging. Therefore, exogenous excitation and inhibition of electron-hole pair recombination are attractive for modulating ROS storms in tumors. Herein, a Ce-doped BiFeO3 (CBFO) piezoelectric sonosensitizer to modulate ROS generation and realize a synergistic mechanism of CDT/sonodynamic therapy and piezodynamic therapy (PzDT) is proposed. The mixed Fe2+ and Ce3+ can implement a circular Fenton/Fenton-like reaction in the tumor microenvironment. Abundant ·OH can be generated by ultrasound (US) stimulation to enhance CDT efficacy. As a typical piezoelectric sonosensitizer, CBFO can produce O2 - owing to the enhanced polarization by the US, resulting in the motion of charge carriers. In addition, CBFO can produce a piezoresponse irradiated upon US, which accelerates the migration rate of electrons/holes in opposite directions and results in energy band bending, further achieving toxic ROS production and realizing PzDT. Density functional theory calculations confirmed that Ce doping shortens the diffusion of electrons and improves the conductivity and catalytic activity of CBFO. This distinct US-enhanced strategy emphasizes the effects of doping engineering and piezoelectric-optimized therapy and shows great potential for the treatment of malignant tumors.

Defect-Engineered Tin Disulfide Nanocarriers as "Precision-Guided Projectile" for Intensive Synergistic Therapy.

Nanoformulations with endogenous/exogenous stimulus-responsive characteristics show great potential in tumor cell elimination with minimal adverse effects and high precision. Herein, an intelligent nanotheranostic platform (denoted as TPZ@Cu-SnS2-x /PLL) for tumor microenvironment (TME) and near-infrared light (NIR) activated tumor-specific therapy is constructed. Copper (Cu) doping and the resulting sulfur vacancies can not only improve the response range of visible light but also improve the separation efficiency of photogenerated carriers and increase the carrier density, resulting in the ideal photothermal and photodynamic performance. Density functional theory calculations revealed that the introduction of Cu and resulting sulfur vacancies can induce electron redistribution, achieving favorable photogenerated electrons. After entering cells through endocytosis, the TPZ@Cu-SnS2-x /PLL nanocomposites show the pH responsivity property for the release of the TPZ selectively within the acidic TME, and the released Cu2+ can first interact with local glutathione (GSH) to deplete GSH with the production of Cu+ . Subsequently, the Cu+ -mediated Fenton-like reaction can decompose local hydrogen peroxide into hydroxyl radicals, which can also be promoted by hyperthermia derived from the photothermal effect for tumor cell apoptosis. The integration of photoacoustic/computed tomography imaging-guided NIR phototherapy, TPZ-induced chemotherapy, and GSH-elimination/hyperthermia enhanced chemodynamic therapy results in synergistic therapeutic outcomes without obvious systemic toxicity in vivo.

Synergizing Pyroelectric Catalysis and Enzyme Catalysis: Establishing a Reciprocal and Synergistic Model to Enhance Anti-Tumor Activity.

Nanozyme activity is greatly weakened by the microenvironment and multidrug resistance of tumor cells. Hence, a bi-catalytic nanoplatform, which promotes the anti-tumor activity through "charging empowerment" and "mutual complementation" processes involved in enzymatic and pyroelectric catalysis, by loading ultra-small nanoparticles (USNPs) of pyroelectric ZnSnO3 onto MXene nanozyme (V2 CTx nanosheets), is developed. Here, the V2 CTx nanosheets exhibit enhanced peroxidase activity by reacting V3+ with H2 O2 to generate toxic ·OH, accelerated by the near-infrared (NIR) light mediated heat effect. The resulting V4+ is then converted to V3+ by oxidizing endogenous glutathione (GSH), realizing an enzyme-catalyzed cycle. However, the cycle will lose its persistence once GSH is insufficient; nevertheless, the pyroelectric charges generated by ZnSnO3 USNPs continuously support the V4+ /V3+ conversion and ensure nanoenzyme durability. Moreover, the hyperthermia arising from the V2 CTx nanosheets by NIR irradiation results in an ideal local temperature gradient for the ZnSnO3 USNPs, giving rise to an excellent pyroelectric catalytic effect by promoting band bending. Furthermore, polarized charges increase the tumor cell membrane permeability and facilitate nanodrug accumulation, thereby resolving the multidrug resistance issue. Thus, the combination of pyroelectric and enzyme catalysis together with the photothermal effect solves the dilemma of nanozymes and improves the antitumor efficiency.

CeO2 and Glucose Oxidase Co-Enriched Ti3C2Tx MXene for Hyperthermia-Augmented Nanocatalytic Cancer Therapy.

Foreseen as foundational in forthcoming oncology interventions are multimodal therapeutic systems. Nevertheless, the tumor microenvironment (TME), marked by heightened glucose levels, hypoxia, and scant concentrations of endogenous hydrogen peroxide could potentially impair their effectiveness. In this research, two-dimensional (2D) Ti3C2 MXene nanosheets are engineered with CeO2 nanozymes and glucose oxidase (GOD), optimizing them for TME, specifically targeting cancer therapy. Following our therapeutic design, CeO2 nanozymes, embodying both peroxidase-like and catalase-like characteristics, enable transformation of H2O2 into hydroxyl radicals for catalytic therapy while also producing oxygen to mitigate hypoxia. Concurrently, GOD metabolizes glucose, thereby augmenting H2O2 levels and disrupting the intracellular energy supply. When subjected to a near-infrared laser, 2D Ti3C2 MXene accomplishes photothermal therapy (PTT) and photodynamic therapy (PDT), additionally amplifying cascade catalytic treatment via thermal enhancement. Empirical evidence demonstrates robust tumor suppression both in vitro and in vivo by the CeO2/Ti3C2-PEG-GOD nanocomposite. Consequently, this integrated approach, which combines PTT/PDT and enzymatic catalysis, could offer a valuable blueprint for the development of advanced oncology therapies.

Phase Engineered Cux S-Ag2 S with Photothermoelectric Activity for Enhanced Multienzyme Activity and Dynamic Therapy.

The insufficient exposure sites and active site competition of multienzyme are the two main factors to hinder its therapeutic effect. Here, a phase-junction nanomaterial (amorphous-crystalline Cux S-Ag2 S) is designed and prepared through a simple room temperature ion-exchange process. A small amount of Ag+ is added into Cu7 S4 nanocrystals, which transforms Cu7 S4 into amorphous phased Cux S and produces crystalline Ag2 S simultaneously. In this structure, the overhanging bonds on the amorphous Cux S surface provide abundant active sites for optimizing the therapeutic activity. Meanwhile, the amorphous state enhances the photothermal effect through non-radiative relaxation, and due to its low thermal resistance, phase-junction Cux S-Ag2 S forms a significant temperature gradient to unlock the optimized thermo-electrodynamic therapy. Furthermore, benefiting from the high asymmetry of the amorphous state, the material forms a spin-polarized state that can effectively inhibit electron-hole recombination. In this way, the thermoelectric effect can facilitate the enzyme-catalyzed cycle by providing electrons and holes, enabling an enhanced coupling of thermoelectric therapy with multienzyme activity, which induces excellent anti-tumor performance. More importantly, the catalytic process simulated by density-functional theory proves that Ag+ alleviates the burden on the Cu sites through favorable adsorption of O2 and prevents active site competition.

Three-Step Depletion Strategy of Glutathione: Tunable Metal-Organic-Framework-Engineered Nanozymes for Driving Oxidative/Nitrative Stress to Maximize Ferroptosis Therapy.

Ferroptosis is a novel type of nonapoptotic programmed cell death involving the accumulation of lipid peroxidation (LPO) to a lethal threshold. Herein, we propose tunable zeolitic imidazolate framework (ZIFs)-engineered biodegradable nanozymes for ferroptosis mediated by both reactive oxygen species (ROS) and nitrogen species (RNS). l-Arginine is utilized as an exogenous nitric oxide donor and loaded into hollow ZIFs@MnO2 artificial nanozymes, which are formed by etching ZIFs with potassium permanganate and simultaneously generating a MnO2 shell in situ. The constructed nanozymes with multienzyme-like activities including peroxidase, oxidase, and catalase can release satisfactory ROS and RNS through a cascade reaction, consequently promoting the accumulation of LPO. Furthermore, it can improve the efficiency of ferroptosis through a three-step strategy of glutathione (GSH) depletion; that is, the outer MnO2 layer consumes GSH under slightly acidic conditions and RNS downregulates SLC7A11 and glutathione reductase, thus directly inhibiting GSH biosynthesis and indirectly preventing GSH regeneration.

Employing Piezoelectric Mg2+-Doped Hydroxyapatite to Target Death Receptor-Mediated Necroptosis: A Strategy for Amplifying Immune Activation.

Although immunogenic cell death (ICD) inducers evidently enhance the effectiveness of immunotherapy, their potential is increasingly restricted by the development of apoptosis resistance in tumor cells, poor immunogenicity, and low T-cell immune responsiveness. In this study, for the first time, piezoelectrically catalyzed Mg2+-doped hydroxyapatite (Mg-HAP) nanoparticles, which are coated with a mesoporous silica layer and loaded with ONC201 as an agonist to specifically target the death receptor DR5 on tumor cells, ultimately developing an Mg-HAP@MS/ONC201 nanoparticle (MHMO NP) system, are engineered. Owing to its excellent piezoelectric properties, MHMO facilitates the release of a significant amount of reactive oxygen species and Ca2+ within tumor cells, effectively promoting the upregulation of DR5 expression and inducing tumor cell necroptosis to ultimately overcome apoptosis resistance. Concurrently, Mg2+ released in the tumor microenvironment promotes CD8+ T receptor activation in response to the antitumor immune reaction induced by ICD. Using RNA-seq analysis, it is elucidated that MHMO can activate the NF-κB pathway under piezoelectric catalysis, thus inducing M1-type macrophage polarization. In summary, a dual-targeting therapy system that targets both tumor cells and the tumor microenvironment under piezoelectric catalysis is designed. This system holds substantial potential for advancements in tumor immunotherapy.

Recent Advances in Metal-Hydride-Based Disease Treatment.

In comparison to traditional antioxidant treatment methods, the use of hydrogen to eliminate reactive oxygen species from the body has the advantages of high biological safety, strong selectivity, and high clearance rate. As an energy storage material, metal hydrides have been extensively studied and used in transporting hydrogen as clean energy, which can achieve a high hydrogen load and controlled hydrogen release. Considering the antioxidant properties of hydrogen and the delivery ability of metal hydrides, metal-hydride-based disease treatment strategies have attracted widespread attention. Up to now, metal hydrides have been reported for the treatment of tumors and a range of inflammation-related diseases. However, limited by the insufficient investment, the use of metal hydrides in disease treatment still has many shortcomings, such as low targeting efficiency, limited therapeutic activity, and complex material preparation process. Particularly, metal hydrides have been found to have a series of optical, acoustic, and catalytic properties when scaled up to the nanoscale, and these properties are also widely used to promote disease treatment effects. From this new perspective, we comprehensively summarize the very recent research progress on metal-hydride-based disease treatment in this review. Ultimately, the challenges and prospects of such a burgeoning cancer theranostics modality are outlooked to provide inspiration for the further development and clinical translation of metal hydrides.

A "One Arrow Three Eagle" Strategy to Improve CM-272 Primed Bladder Cancer Immunotherapy.

Immunotherapy using an immune-checkpoint blockade has significantly improved its therapeutic effects. CM-272, which is a novel epigenetic inhibitor of G9a, induces immunogenic cell death (ICD) for recovering the sensitivity to anti-PD-1 antibodies; however, the efficacy of CM-272 is greatly limited by promoting the transcription activity of HIF-1α to form a hypoxic environment. Here, a Fe3+ -based nanoscale metal-organic framework (MIL-53) is used to load CM-272 (ultra-high loading rate of 56.4%) for realizing an MIL-53@CM-272 nanoplatform. After entering bladder cancer cells, Fe3+ not only promotes the decomposition of H2 O2 into O2 for O2 -compensated sonodynamic therapy but reduces the high level of glutathione in the tumor microenvironment (TME) for enhancing reactive oxygen species, including ferroptosis and apoptosis. MIL-53 carriers can be degraded in response to the TME, accelerating the release of CM-272, which helps achieve the maximum effectiveness in an O2 -sufficient TME by attenuating drug resistance. Furthermore, MIL-53@CM-272 enhances dendritic cell maturation and synergistically combines it with an anti-programmed cell death protein 1 antibody during the study of immune-related pathways in the transcriptomes of bladder cancer cells using RNA-seq. This study presents the first instance of amalgamating nanomedicine with CM-272, inducing apoptosis, ferroptosis, and ICD to achieve the "one arrow three eagle" effect.

Architecture of Vanadium-Based MXene Dysregulating Tumor Redox Homeostasis for Amplified Nanozyme Catalytic/Photothermal Therapy.

Taking the significance of the special microenvironment for tumor cell survival into account, disrupting tumor redox homeostasis is highly prospective for improving therapeutic efficacy. Herein, a multifunctional 2D vanadium-based MXene nanoplatform, V4 C3 /atovaquone@bovine albumin (V4 C3 /ATO@BSA, abbreviated as VAB) has been elaborately constructed for ATO-enhanced nanozyme catalytic/photothermal therapy. The redox homeostasis within the tumor cells is eventually disrupted, showing a remarkable anti-tumor effect. The VAB nanoplatform with mixed vanadium valence states can induce a cascade of catalyzed reactions in the tumor microenvironment, generating plenty of reactive oxygen species (ROS) with effective glutathione consumption to amplify oxidative stress. Meanwhile, the stable and strong photothermal effect of VAB under near-infrared irradiation not only causes the necrosis of tumor cells, but also improves its peroxidase-like activity. In addition, the release of ATO can effectively alleviate endogenous oxygen consumption to limit triphosadenine formation and inhibit mitochondrial respiration. As a result, the expression of heat shock proteins is effectively suppressed to overcome thermoresistance and the production of ROS can be further promoted due to mitochondrial injury. Moreover, VAB also presents high photoacoustic and photothermal imaging performances. In brief, the multifunctional nanoplatform can provide ATO-enhanced nanozyme catalytic/photothermal therapy with broadening the biomedical applications of vanadium-based MXene.

Revealing the Mutually Enhanced Mechanism of Necroptosis and Immunotherapy Induced by Defect Engineering and Piezoelectric Effect.

Owing to low immunogenicity-induced immune escape and short-term circulating immune responses, the efficiency of immunotherapy is unsatisfactory. Therefore, triggering immunogenic cell death and establishing a long-term, mutually reinforced treatment modality are urgent challenges. In this study, ultrathin CaBi2 Nb2 O9 nanosheets with tunable oxygen vacancies (abbreviated as CBNO-OV1) are prepared for synergistic necroptosis and immunotherapy. The optimized vacancy concentration significantly improves the piezoelectric effect under ultrasound irradiation, thereby considerably improving the generation of reactive oxygen species (ROS). Density functional theory shows that oxygen vacancies can improve the efficiency of electron hole separation by suppressing their recombination, thus resulting in enhanced piezocatalytic activity. Moreover, the piezoelectric effect improves the permeability of tumor cell membranes, thus resulting in Ca2+ influx. Additionally, CBNO-OV1 also releases a portion of Ca2+ , which induces necroptosis assisted by explosive ROS. Ribonucleic acid transcription tests suggest the mechanisms associated with immune response activation and necroptosis. More importantly, necroptosis can trigger a significant immune response in vivo, thus activating macrophage M1 polarization through the NF-kappa B pathway and promoting T-cell differentiation.Tumor Necrosis Factor-α differentiated from macrophages conversely promotes necroptosis, thus realizing a mutually enhanced effect. This study demonstrates the feasibility of mutually reinforced necroptosis and immunotherapy for amplifying tumor efficacy.

A bubble-enhanced lanthanide-doped up/down-conversion platform with tumor microenvironment response for dual-modal photoacoustic and near-infrared-II fluorescence imaging.

As an important tumor diagnosis strategy in precision medicine, multimodal imaging has been widely studied. However, the weak imaging signal with low spatial resolution and the constant signal of lack of specific activation severely limit its disease diagnosis. Herein, a bubble-enhanced lanthanide-based up/down-conversion platform with tumor microenvironment response for dual-mode imaging, LDNP@DMSN-Au@CaCO3 nanoparticles (named as LDAC NPs) were successfully developed. Combining the advantages of photoacoustic imaging (PAI) and the second near-infrared window (NIR-II) fluorescence imaging (FI), significantly improved the accuracy of diseases diagnosis. LDAC NPs with flower-like structure were synthesized through the encapsulation of uniform lanthanide-doped nanoparticles (NaYbF4:Ce,Er@NaYF4 named LDNPs) with dendritic mesoporous silica (DMSN). The gold nanoparticles (Au NPs) were then in situ grown on the surface of DMSN and the surface were finally coated with a layer of calcium carbonate (CaCO3). Under the excitation of the 980 nm laser, LDNPs showed strong emission of NIR-II at 1550 nm due to the doping of Ce and Er ions, showcasing excellent spatial resolution and deep tissue penetration characteristics, while the resulting visible light emission (540 nm) enables Au NPs to generate PAI signals with the aid of LDNPs via the fluorescence resonance energy transfer effect. In acidic tumoral environment, CaCO3 layer could produce CO2 microbubbles, and the PAI signals of LDAC NPs could be further enhanced with the generation of CO2 bubbles due to the bubble cavitation effect. Simultaneously, the NIR-II FI of LDAC NPs was self-enhanced with the degradation of the CaCO3. This intelligent nanoparticle with stimulus-activated dual-mode imaging capability holds great promise in future precision diagnostics.

Mitochondria-targeting Cu3VS4 nanostructure with high copper ionic mobility for photothermoelectric therapy.

Thermoelectric therapy has emerged as a promising treatment strategy for oncology, but it is still limited by the low thermoelectric catalytic efficiency at human body temperature and the inevitable tumor thermotolerance. We present a photothermoelectric therapy (PTET) strategy based on triphenylphosphine-functionalized Cu3VS4 nanoparticles (CVS NPs) with high copper ionic mobility at room temperature. Under near-infrared laser irradiation, CVS NPs not only generate hyperthermia to ablate tumor cells but also catalytically yield superoxide radicals and induce endogenous NADH oxidation through the Seebeck effect. Notably, CVS NPs can accumulate inside mitochondria and deplete NADH, reducing ATP synthesis by competitively inhibiting the function of complex I, thereby down-regulating the expression of heat shock proteins to relieve tumor thermotolerance. Both in vitro and in vivo results show notable tumor suppression efficacy, indicating that the concept of integrating PTET and mitochondrial metabolism modulation is highly feasible and offers a translational promise for realizing precise and efficient cancer treatment.

Deep Insight of Design, Mechanism, and Cancer Theranostic Strategy of Nanozymes.

Since the discovery of enzyme-like activity of Fe3O4 nanoparticles in 2007, nanozymes are becoming the promising substitutes for natural enzymes due to their advantages of high catalytic activity, low cost, mild reaction conditions, good stability, and suitable for large-scale production. Recently, with the cross fusion of nanomedicine and nanocatalysis, nanozyme-based theranostic strategies attract great attention, since the enzymatic reactions can be triggered in the tumor microenvironment to achieve good curative effect with substrate specificity and low side effects. Thus, various nanozymes have been developed and used for tumor therapy. In this review, more than 270 research articles are discussed systematically to present progress in the past five years. First, the discovery and development of nanozymes are summarized. Second, classification and catalytic mechanism of nanozymes are discussed. Third, activity prediction and rational design of nanozymes are focused by highlighting the methods of density functional theory, machine learning, biomimetic and chemical design. Then, synergistic theranostic strategy of nanozymes are introduced. Finally, current challenges and future prospects of nanozymes used for tumor theranostic are outlined, including selectivity, biosafety, repeatability and stability, in-depth catalytic mechanism, predicting and evaluating activities.

Porous Molybdenum Nitride Nanosphere as Carrier-Free and Efficient Nitric Oxide Donor for Synergistic Nitric Oxide and Chemo/Sonodynamic Therapy.

Given its abundant physiological functions, nitric oxide (NO) has attracted much attention as a cancer therapy. The sensitive release and great supply capacity are significant indicators of NO donors and their performance. Here, a transition metal nitride (TMN) MoN@PEG is adopted as an efficient NO donor. The release process starts with H+-triggered denitrogen owing to the high electronegativity of the N atom and weak Mo-N bond. Then, these active NHx are oxidized by O2 and other reactive oxygen species (ROS) to form NO, endowing specific release to the tumor microenvironment (TME). With a porous nanosphere structure (80 nm), MoN@PEG does not require an extra carrier for NO delivery, contributing to ultrahigh atomic utilization for outstanding release ability (94.1 ± 5.6 µM). In addition, it can also serve as a peroxidase and sonosensitizer for anticancer treatment. To further improve the charge separation, MoN-Pt@PEG was prepared to enhance the sonodynamic therapy (SDT) effect. Accordingly, ultrasound (US) further promotes NO generation due to more ROS generation, facilitating in situ peroxynitrite (·ONOO-) generation with great cytotoxicity. At the same time, the nanostructure also degrades gradually, leading to high elimination (94.6%) via feces and urine within 14-day. The synergistic NO and chemo-/sono-dynamic therapy brings prominent antitumor efficiency and further activates the immune response to inhibit metastasis and recurrence. This work develops a family of NO donors that would further widen the application of NO therapy in other fields.

Highly active, ultra-low loading single-atom iron catalysts for catalytic transfer hydrogenation.

Highly effective and selective noble metal-free catalysts attract significant attention. Here, a single-atom iron catalyst is fabricated by saturated adsorption of trace iron onto zeolitic imidazolate framework-8 (ZIF-8) followed by pyrolysis. Its performance toward catalytic transfer hydrogenation of furfural is comparable to state-of-the-art catalysts and up to four orders higher than other Fe catalysts. Isotopic labeling experiments demonstrate an intermolecular hydride transfer mechanism. First principles simulations, spectroscopic calculations and experiments, and kinetic correlations reveal that the synthesis creates pyrrolic Fe(II)-plN3 as the active center whose flexibility manifested by being pulled out of the plane, enabled by defects, is crucial for collocating the reagents and allowing the chemistry to proceed. The catalyst catalyzes chemoselectively several substrates and possesses a unique trait whereby the chemistry is hindered for more acidic substrates than the hydrogen donors. This work paves the way toward noble-metal free single-atom catalysts for important chemical reactions.

Design and Mechanism Insight of Monodispersed AuCuPt Alloy Nanozyme with Antitumor Activity.

The abrogation of the self-adaptive redox evolution of tumors is promising for improving therapeutic outcomes. In this study, we designed a trimetallic alloy nanozyme AuCuPt-PpIX (ACPP), which mimics up to five naturally occurring enzymes: glucose oxidase (GOD), superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and glutathione peroxidase (GPx). Facilitated by these enzyme-mimicking traits, the constructed ACPP nanozymes can not only disrupt the established redox homeostasis in tumors through a series of enzymatic cascade reactions but also achieve cyclic regeneration of the relevant enzyme substrates. Density functional theory (DFT) calculations have theoretically explained the synergistic effect of multimetallic doping and the possible mechanism of enzymatic catalysis. The doped Cu and Pt sites are conducive to the adsorption, activation, and dissociation of reactant molecules, whereas the Au sites are conducive to desorption, which significantly improves catalytic efficiency via a synergistic effect. Additionally, ACPP nanozymes can improve the effect of protoporphyrin (PpIX)-enabled sonodynamic therapy (SDT) by alleviating hypoxia and initiating ferroptosis by inducing lipid peroxidation (LPO) and inhibiting GPX4 activity, thus achieving multimodal synergistic therapy. This study presents a typical paradigm to enable the use of multimetallic alloy nanozymes for the treatment of tumor cells with self-adaptive properties.