Prussian Blue-Derived Nanocomposite Synergized with Calcium Overload for Three-Mode ROS Outbreak Generation to Enhance Oncotherapy.

Calcium overload can lead to tumor cell death. However, because of the powerful calcium channel excretory system within tumor cells, simplistic calcium overloads do not allow for an effective antitumor therapy. Hence, the nanoparticles are created with polyethylene glycol (PEG) donor-modified calcium phosphate (CaP)-coated, manganese-doped hollow mesopores Prussian blue (MMPB) encapsulating glucose oxidase (GOx), called GOx@MMPB@CaP-PEG (GMCP). GMCP with a three-mode enhancement of intratumor reactive oxygen species (ROS) levels is designed to increase the efficiency of the intracellular calcium overload in tumor cells to enhance its anticancer efficacy. The released exogenous Ca2+ and the production of cytotoxic ROS resulting from the perfect circulation of the three-mode ROS outbreak generation that Fenton/Fenton-like reaction and consumption of glutathione from Fe2+/Fe3+and Mn2+/Mn3+ circle, and amelioration of hypoxia from MMPB-guided and GOx-mediated starvation therapy. Photothermal efficacy-induced heat generation owing to MMPB accelerates the above reactions. Furthermore, abundant ROS contribute to damage to mitochondria, and the calcium channels of efflux Ca2+ are inhibited, resulting in a calcium overload. Calcium overload further increases ROS levels and promotes apoptosis of tumor cells to achieve excellent therapy.

Regulating Second Coordination Shell of Ce Atom Site and Reshaping of Carrier Enable Single-Atom Nanozyme to Efficiently Express Oxidase-like Activity.

Single-atom nanozymes (SANs) are considered to be ideal substitutes for natural enzymes due to their high atom utilization. This work reported a strategy to manipulate the second coordination shell of the Ce atom and reshape the carbon carrier to improve the oxidase-like activity of SANs. Internally, S atoms were symmetrically embedded into the second coordination layer to form a Ce-N4S2-C structure, which reduced the energy barrier for O2 reduction, promoted the electron transfer from the Ce atom to O atoms, and enhanced the interaction between the d orbital of the Ce atom and p orbital of O atoms. Externally, in situ polymerization of mussel-inspired polydopamine on the precursor helps capture metal sources and protects the 3D structure of the carrier during pyrolysis. On the other hand, polyethylene glycol (PEG) modulated the interface of the material to enhance water dispersion and mass transfer efficiency. As a proof of concept, the constructed PEG@P@Ce-N/S-C was applied to the multimodal assay of butyrylcholinesterase activity.

The facile and controllable synthesis of ultrafine Sn nanocrystals loaded on carbon black for high-performance lithium storage.

Sn and C nanocomposites are ideal anode materials for high-energy and high-power density lithium ion batteries. However, their facile and controllable synthesis for practical applications is still a critical challenge. In this work, a facile one-step method is developed to controllably synthesize ultrafine Sn nanocrystals (< 5 nm) loaded on carbon black (Sn@C) through Na reducing SnCl4 by mechanical milling. Different from traditional up-down mechanical milling method, this method utilizes mechanical milling to trigger bottom-up reduction reaction of SnCl4. The in-situ formed Sn nanocrystals directly grow on carbon black, which results in the homogeneous composite and the size control of Sn nanocrystals. The obtained Sn@C electrode is revealed to possesses large lithium diffusion coefficient, low lithiation energy barrier and stable electrochemical property during cycle, thus showing excellent lithium storage performance with a high reversible capacity (942 mAh g-1 at a current density of 100 mA g-1), distinguished rate ability (480 mAh g-1 at 8000 mA g-1) and superb cycling performance (730 mAh g-1 at 1000 mA g-1 even after 1000 cycles).

Oxygen Vacancy Piezoelectric Nanosheets Constructed by a Photoetching Strategy for Ultrasound "Unlocked" Tumor Synergistic Therapy.

Piezoelectric dynamic therapy (PzDT) is an effective method of tumor treatment by using piezoelectric polarization to generate reactive oxygen species. In this paper, two-dimensional Cu-doped BiOCl nanosheets with surface vacancies are produced by the photoetching strategy. Under ultrasound, a built-in electric field is generated to promote the electron and hole separation. The separated carriers achieve O2 reduction and GSH oxidation, inducing oxidative stress. The bandgap of BiOCl is narrowed by introducing surface oxygen vacancies, which act as charge traps and facilitate the electron and hole separation. Meanwhile, Cu doping induces chemodynamic therapy and depletes GSH via the transformation from Cu(II) to Cu(I). Both in vivo and in vitro results confirmed that oxidative stress can be enhanced by exogenous ultrasound stimulation, which can cause severe damage to tumor cells. This work emphasizes the efficient strategy of doping engineering and defect engineering for US-activated PzDT under exogenous stimulation.

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.

Stretchable Unsymmetrical Piezoelectric BiO2-x Deposited-Hydrogel as Multimodal Triboelectric Nanogenerators for Biomechanical Motion Harvesting.

Enhancing the output performance of triboelectric nanogenerators (TENGs) is essential for increasing their application in smart devices. Oxygen-vacancy-rich BiO2-x nanosheets (BiO2-x NSs) are advanced-engineered nanomaterials with excellent piezoelectric properties. Herein, a stretchable unsymmetrical BiO2-x NSs deposited-hydrogel made of polyacrylamide (PAM) as a multimodal TENG is rationally fabricated, and the performance of TENG can be tailored by controlling the BiO2-x NSs deposition amount and spatial distribution. The alteration of resistance caused by the Poisson effect of PAM/BiO2-x composite hydrogel (H-BiO2-x) can be used as a piezoresistive sensor, and the piezoelectricity of BiO2-x NSs can effectively enhance the density of transfer charge, thus improving the output performance of the H-BiO2-x-based TENG. In addition, the chemical cross-linking between the BiO2-x NSs and the PAM polymer chain allows the hydrogel electrode to have a higher tensile capacity (867%). Used for biomechanical motion signal detection, the sensors made of H-BiO2-x have high sensitivity (gauge factor = 6.93) and can discriminate a range of forces (0.1-5.0 N) at low frequencies (0.5-2.0 Hz). Finally, the prepared TENG can collect biological energy and convert it into electricity. Consequently, the improved TENG shows a good application prospect as multimodal biomechanical sensors by combining piezoresistive, piezoelectric, and triboelectric effects.

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.

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.

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.

High-Entropy Engineering of Cubic SiP with Metallic Conductivity for Fast and Durable Li-Ion Batteries.

A cost-effective, scalable ball milling process is employed to synthesize the InGeSiP3 compound with a cubic ZnS structure, aiming to address the sluggish reaction kinetics of Si-based anodes for Lithium-ion batteries. Experimental measurements and first-principles calculations confirm that the synthesized InGeSiP3 exhibits significantly higher electronic conductivity, larger Li-ion diffusivity, and greater tolerance to volume change than its parent phases InGe (or Si)P2 or In (or Ge, or Si)P. These improvements stem from its elevated configurational entropy. Multiple characterizations validate that InGeSiP3 undergoes a reversible Li-storage mechanism that involves intercalation, followed by conversion and alloy reactions, resulting in a reversible capacity of 1733 mA h g-1 with an initial Coulombic efficiency of 90%. Moreover, the InGeSiP3-based electrodes exhibit exceptional cycling stability, retaining an 1121 mA h g-1 capacity with a retention rate of ≈87% after 1500 cycles at 2000 mA g-1 and remarkable high-rate capability, achieving 882 mA h g-1 at 10 000 mA g-1. Inspired by the distinctive characteristic of high entropy, the synthesis is extended to high entropy GaCu (or Zn)InGeSiP5, CuZnInGeSiP5, GaCuZnInGeSiP6, InGeSiP2S (or Se), and InGeSiPSSe. This endeavor overcomes the immiscibility of different metals and non-metals, paving the way for the electrochemical energy storage application of high-entropy silicon-phosphides.

Anti-Freezing and Ultrasensitive Zwitterionic Betaine Hydrogel-Based Strain Sensor for Motion Monitoring and Human-Machine Interaction.

Ultrasensitive and reliable conductive hydrogels are significant in the construction of human-machine twinning systems. However, in extremely cold environments, freezing severely limits the application of hydrogel-based sensors. Herein, building on biomimetics, a zwitterionic hydrogel was elaborated for human-machine interaction employing multichemical bonding synergies and experimental signal analyses. The covalent bonds, hydrogen bonds, and electrostatic interactions construct a dense double network structure favorable for stress dispersion and hydrogen bond regeneration. In particular, zwitterions and ionic conductors maintained excellent strain response (99 ms) and electrical sensitivity (gauge factor = 14.52) in the dense hydrogel structure while immobilizing water molecules to enhance the weather resistance (-68 °C). Inspired by the high sensitivity, zwitterionic hydrogel-based strain sensors and remote-control gloves were designed by analyzing the experimental signals, demonstrating promising potential applications within specialized flexible materials and human-machine symbiotic systems.

Effects of the ZrO2 Crystalline Phase and Morphology on the Thermocatalytic Decomposition of Dimethyl Methylphosphonate.

Thermocatalytic decomposition is an efficient purification technology that is potentially applicable to degrading chemical warfare agents and industrial toxic gases. In particular, ZrO2 has attracted attention as a catalyst for the thermocatalytic decomposition of dimethyl methylphosphonate (DMMP), which is a simulant of the nerve gas sarin. However, the influence of the crystal phase and morphology on the catalytic performance of ZrO2 requires further exploration. In this study, monoclinic- and tetragonal-phase ZrO2 (m- and t-ZrO2, respectively) with nanoparticle, flower-like shape and hollow microsphere morphologies were prepared via hydrothermal and solvothermal methods, and their thermocatalytic decomposition of DMMP was systematically investigated. For a given morphology, m-ZrO2 performed better than t-ZrO2. For a given crystalline phase, the morphology of hollow microspheres resulted in the longest protection time. The exhaust gases generated by the thermocatalytic decomposition of DMMP mainly comprised H2, CO2, H2O and CH3OH, and the by-products were phosphorus oxide species. Thus, the deactivation of ZrO2 was attributed to the deposition of these phosphorous oxide species on the catalyst surface. These results are expected to help guide the development of catalysts for the safe disposal of chemical warfare agents.

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 (V2CTx nanosheets), is developed. Here, the V2CTx nanosheets exhibit enhanced peroxidase activity by reacting V3+ with H2O2 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 V2CTx 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.

Phase Engineered CuxS-Ag2S 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 CuxS-Ag2S) is designed and prepared through a simple room temperature ion-exchange process. A small amount of Ag+ is added into Cu7S4 nanocrystals, which transforms Cu7S4 into amorphous phased CuxS and produces crystalline Ag2S simultaneously. In this structure, the overhanging bonds on the amorphous CuxS 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 CuxS-Ag2S 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.

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.

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.

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.

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.