Piezoelectric Catalysis Induces Tumor Cell Senescence to Boost Chemo-Immunotherapy.

Cellular senescence, a vulnerable state of growth arrest, has been regarded as a potential strategy to weaken the resistance of tumor cells, leading to dramatic improvements in treatment efficacy. However, a selective and efficient strategy for inducing local tumor cellular senescence has not yet been reported. Herein, piezoelectric catalysis is utilized to reduce intracellular NAD+ to NADH for local tumor cell senescence for the first time. In detail, a biocompatible nanomedicine (BTO/Rh-D@M) is constructed by wrapping the piezoelectric BaTiO3/(Cp*RhCl2)2 (BTO/Rh) and doxorubicin (DOX) in the homologous cytomembrane with tumor target. After tumors are stimulated by ultrasound, negative and positive charges are generated on the BTO/Rh by piezoelectric catalysis, which reduce the intracellular NAD+ to NADH for cellular senescence and oxidize H2O to reactive oxygen species (ROS) for mitochondrial damage. Thus, the therapeutic efficacy of tumor immunogenic cell death-induced chemo-immunotherapy is boosted by combining cellular senescence, DOX, and ROS. The results indicate that 23.9% of the piezoelectric catalysis-treated tumor cells senesced, and solid tumors in mice disappeared completely after therapy. Collectively, this study highlights a novel strategy to realize cellular senescence utilizing piezoelectric catalysis and the significance of inducing tumor cellular senescence to improve therapeutic efficacy.

The Piezocatalytic Degradation of Sulfadiazine by Lanthanum-Doped Barium Titanate.

Piezocatalysis, a heterogeneous catalytic technique, leverages the periodic electric field changes generated by piezoelectric materials under external forces to drive carriers for the advanced oxidation of organic pollutants. Antibiotics, as emerging trace organic pollutants in water sources, pose a potential threat to animals and drinking water safety. Thus, piezoelectric catalysis can be used to degrade trace organic pollutants in water. In this work, BaTiO3 and La-doped BaTiO3 were synthesized using an improved sol-gel-hydrothermal method and used as piezocatalytic materials to degrade sulfadiazine (SDZ) with ultrasound activation. High-crystallinity products with nano cubic and spherical morphologies were successfully synthesized. An initial concentration of SDZ ranging from 1 to 10 mg/L, a catalysis dosage range from 1 to 2.5 mg/mL, pH, and the background ions in the water were considered as influencing factors and tested. The reaction rate constant was 0.0378 min-1 under the optimum working conditions, and the degradation efficiency achieved was 89.06% in 60 min. La-doped BaTiO3 had a better degradation efficiency, at 14.98% on average, compared to undoped BaTiO3. Further investigations into scavengers revealed a partially piezocatalytic process for the degradation of SDZ. In summary, our work provides an idea for green environmental protection in dealing with new types of environmental pollution.

Triphasic Hydroxysilylation of Alkenes by Mechanically Piezoelectric Catalysis.

The 1,2-hydroxysilylation of alkenes is crucial for synthesizing organosilicon compounds which are key intermediates in material science, pharmaceuticals, and organic synthesis. The development of strategies employing hydrogen atom transfer pathways is currently hindered by the existence of various competing reactions. Herein, we reported a novel mechanochemical strategy for the triphasic 1,2-hydroxysilylation of alkenes through a single-electron-transfer pathway. Our approach not only circumvents competitive reactions to enable the first-ever 1,2-hydroxysilylation of unactivated alkenes but also pioneers the research in mechanic force-induced triphasic reactions under ambient conditions. This gentle method offers excellent compatibility with various functional groups, operates under simple and solvent-free conditions, ensures rapid reaction time. Preliminary mechanistic investigations suggest that silylboronate can be transformed to a silicon radical by highly polarized Li2TiO3 particles and oxygen under ball-milling condition.

Preparation of Nanocomposites for Antibacterial Orthodontic Invisible Appliance Based on Piezoelectric Catalysis.

Compared to fixed orthodontic appliances with brackets, thermoplastic invisible orthodontic aligners offer several advantages, such as high aesthetic performance, good comfort, and convenient oral health maintenance, and are widely used in orthodontic fields. However, prolonged use of thermoplastic invisible aligners may lead to demineralization and even caries in most patients' teeth, as they enclose the tooth surface for an extended period. To address this issue, we have created PETG composites that contain piezoelectric barium titanate nanoparticles (BaTiO3NPs) to obtain antibacterial properties. First, we prepared piezoelectric composites by incorporating varying amounts of BaTiO3NPs into PETG matrix material. The composites were then characterized using techniques such as SEM, XRD, and Raman spectroscopy, which confirmed the successful synthesis of the composites. We cultivated biofilms of Streptococcus mutans (S. mutans) on the surface of the nanocomposites under both polarized and unpolarized conditions. We then activated piezoelectric charges by subjecting the nanocomposites to 10 Hz cyclic mechanical vibration. The interactions between the biofilms and materials were evaluated by measuring the biofilm biomass. The addition of piezoelectric nanoparticles had a noticeable antibacterial effect on both the unpolarized and polarized conditions. Under polarized conditions, nanocomposites demonstrated a greater antibacterial effect than under unpolarized conditions. Additionally, as the concentration of BaTiO3NPs increased, the antibacterial rate also increased, with the surface antibacterial rate reaching 67.39% (30 wt% BaTiO3NPs). These findings have the potential for application in wearable, invisible appliances to improve clinical services and reduce the need for cleaning methods.

Contact-Piezoelectric Bi-Catalysis of an Electrospun ZnO@PVDF Composite Membrane for Dye Decomposition.

The treatment of organic pollutants in wastewater is becoming a great challenge for social development. Herein, a novel contact-piezoelectric bi-catalysis of a ZnO@ PVDF composite membrane was prepared by electrospinning technology. The obtained ZnO@PVDF composite membranes is superior to the pure PVDF membrane in decomposing methyl orange (MO) under ultrasonication at room temperature, which is mainly attributed to the synergy effect of the contact-electro-catalysis of dielectric PVDF, as well as the piezoelectric catalysis of tetrapodal ZnO and the ß-phase of PVDF. The heterostructure of the piezoelectric-ZnO@dielectric-PVDF composite is beneficial in reducing the electron/hole pair recombination. As compared to the pure PVDF membrane, the catalytic degradation efficiency of the ZnO@PVDF composite membrane was improved by 444.23% under ultrasonication. Moreover, the reusability and stability of the composite membrane are comparable to those of the traditional powdered catalyst. This work offers a promising strategy for improving the pollutant degradation by combining contact-electro-catalysis with piezoelectric catalysis.

Macroscopic Polarization Enhancement Promoting Photo- and Piezoelectric-Induced Charge Separation and Molecular Oxygen Activation.

Efficient photo- and piezoelectric-induced molecular oxygen activation are both achieved by macroscopic polarization enhancement on a noncentrosymmetric piezoelectric semiconductor BiOIO3 . The replacement of V5+ ions for I5+ in IO3 polyhedra gives rise to strengthened macroscopic polarization of BiOIO3 , which facilitates the charge separation in the photocatalytic and piezoelectric catalytic process, and renders largely promoted photo- and piezoelectric induced reactive oxygen species (ROS) evolution, such as superoxide radicals (. O2- ) and hydroxyl radicals (. OH). This work advances piezoelectricity as a new route to efficient ROS generation, and also discloses macroscopic polarization engineering on improvement of multi-responsive catalysis.

Piezocatalytically-induced controllable mineralization scaffold with bone-like microenvironment to achieve endogenous bone regeneration.

Orderly hierarchical structure with balanced mechanical, chemical, and electrical properties is the basis of the natural bone microenvironment. Inspired by nature, we developed a piezocatalytically-induced controlled mineralization strategy using piezoelectric polymer poly-L-lactic acid (PLLA) fibers with ordered micro-nano structures to prepare biomimetic tissue engineering scaffolds with a bone-like microenvironment (pcm-PLLA), in which PLLA-mediated piezoelectric catalysis promoted the in-situ polymerization of dopamine and subsequently regulated the controllable growth of hydroxyapatite crystals on the fiber surface. PLLA fibers, as analogs of mineralized collagen fibers, were arranged in an oriented manner, and ultimately formed a bone-like interconnected pore structure; in addition, they also provided bone-like piezoelectric properties. The uniformly sized HA nanocrystals formed by controlled mineralization provided a bone-like mechanical strength and chemical environment. The pcm-PLLA scaffold could rapidly recruit endogenous stem cells, and promote their osteogenic differentiation by activating cell membrane calcium channels and PI3K signaling pathways through ultrasound-responsive piezoelectric signals. In addition, the scaffold also provided a suitable microenvironment to promote macrophage M2 polarization and angiogenesis, thereby enhancing bone regeneration in skull defects of rats. The proposed piezocatalytically-induced controllable mineralization strategy provides a new idea for the development of tissue engineering scaffolds that can be implemented for multimodal physical stimulation therapy.

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.

Ultrasonic-enhanced photocatalysis through piezoelectric and cavitation effects for lignin depolymerization.

Although a promising method for lignin depolymerization, photocatalysis faces the challenge of low efficiency. In this study, MoS2/ZnO heterojunction catalysts, endowed with piezocatalysis and photocatalytic capabilities, were crafted through Zn ion intercalation for the depolymerization of phenoxyphenylethanol (PP-ol) and alkali lignin. Then, the synergistic interplay between ultrasonic-induced piezoelectric fields and heterojunctions was analyzed. The amalgamation of the piezoelectric field and heterojunction in MoS2/ZnO catalysts resulted in a diminished photogenerated hole/electron recombination efficiency, thereby fostering the generation of ·OH during the reaction. This pivotal role of ·OH emerged as a crucial reactive substance, converting 95.8 % of PP-ol through ß-O-4 bond breaking within a 3-h treatment. By incorporating ultrasonic, the contact probability of PP-ol with the catalyst was significantly improved, resulting in efficient conversion even with a reduced amount of acetonitrile in the solvent system (20 %). Furthermore, ultrasonic-light methods show high efficiency for depolymerizing Alkali lignin (AL), with 33.2 % of lignin undergoing depolymerization in a 4-h treatment. This treatment simultaneously reduces the molecular weight of AL and cleaves numerous chemical bonds within it. Overall, this work presents a green approach to lignin depolymerization, providing insights into the synergistic action of ultrasonic and photocatalysis.

Tumor microenviroment-responsive self-assembly of barium titanate nanoparticles with enhanced piezoelectric catalysis capabilities for efficient tumor therapy.

Catalytic therapy based on piezoelectric nanoparticles has become one of the effective strategies to eliminate tumors. However, it is still a challenge to improve the tumor delivery efficiency of piezoelectric nanoparticles, so that they can penetrate normal tissues while specifically aggregating at tumor sites and subsequently generating large amounts of reactive oxygen species (ROS) to achieve precise and efficient tumor clearance. In the present study, we successfully fabricated tumor microenvironment-responsive assembled barium titanate nanoparticles (tma-BTO NPs): in the neutral pH environment of normal tissues, tma-BTO NPs were monodisperse and possessed the ability to cross the intercellular space; whereas, the acidic environment of the tumor triggered the self-assembly of tma-BTO NPs to form submicron-scale aggregates, and deposited in the tumor microenvironment. The self-assembled tma-BTO NPs not only caused mechanical damage to tumor cells; more interestingly, they also exhibited enhanced piezoelectric catalytic efficiency and produced more ROS than monodisperse nanoparticles under ultrasonic excitation, attributed to the mutual extrusion of neighboring particles within the confined space of the assembly. tma-BTO NPs exhibited differential cytotoxicity against tumor cells and normal cells, and the stronger piezoelectric catalysis and mechanical damage induced by the assemblies resulted in significant apoptosis of mouse breast cancer cells (4T1); while there was little damage to mouse embryo osteoblast precursor cells (MC3T3-E1) under the same treatment conditions. Animal experiments confirmed that peritumoral injection of tma-BTO NPs combined with ultrasound therapy can effectively inhibit tumor progression non-invasively. The tumor microenvironment-responsive self-assembly strategy opens up new perspectives for future precise piezoelectric-catalyzed tumor therapy.

Ultrasonic-driven degradation of organic pollutants using piezoelectric catalysts WS2/Bi2WO6 heterojunction composites.

Water pollution has been made worse by the widespread use of organic dyes and their discharge, which has coincided with the industry's rapid development. Piezoelectric catalysis, as an effective wastewater purification method with promising applications, can enhance the catalyst activity by collecting tiny vibrations in nature and is not limited by sunlight. In this work, we designed and synthesized intriguing WS2/Bi2WO6 heterojunction nanocomposites, investigated their shape, structure, and piezoelectric characteristics using a range of characterization techniques, and used ultrasound to accelerate the organic dye Rhodamine B (RhB) degradation in wastewater. In comparison to the pristine monomaterials, the results demonstrated that the heterojunction composites demonstrated excellent degradation and stability of RhB under ultrasonic circumstances. The existence of heterojunctions and the internal piezoelectric field created by ultrasonic driving work in concert to boost catalytic performance, and the organic dye's rate of degradation is further accelerated by the carriers that are mutually transferred between the composites.

Sono-promoted piezocatalysis and low-dose drug penetration for personalized therapy via tumor organoids.

Chemotherapy is a widely used cancer treatment, however, it can have notable side effects owing to the high-doses of drugs administered. Sonodynamic therapy (SDT) induced by sonosensitizers has emerged as a promising approach to treat cancer, however, there is limited research evaluating its therapeutic effects on human tumors. In this study, we introduced a dual therapy that combines low-dose chemotherapeutic drugs with enhanced sonodynamic therapy, utilizing barium titanate (BaTiO3, BTO) nanoparticles (NPs) as sonosensitizers to treat tumor organoids. We demonstrated that ultrasound could improve the cellular uptake of chemotherapy drugs, while the chemotherapeutic effect of the drugs made it easier for BTO NPs to enter tumor cells, and the dual therapy synergistically inhibited tumor cell viability. Moreover, different patient-derived tumor organoids exhibited different sensitivities to this therapy, highlighting the potential to evaluate individual responses to combination therapies prior to clinical intervention. Furthermore, this dual therapy exhibited therapeutic effects equivalent to those of high-dose chemotherapy drugs on drug-resistant tumor organoids and showed the potential to enhance the efficacy of killing drug-resistant tumors. In addition, the biosafety of the BTO NPs was successfully verified in live mice via oral administration. This evidence confirms the reliable and safe nature of the dual therapy approach, making it a feasible option for precise and personalized therapy in clinical applications.

Unexpected Emergence of Carbon-Centered Radicals from Piezoelectric Effect in Oleic Acid-Capped BaTiO3.

The utilization of alkyl radicals (•R) for hypoxic tumor therapy has great prospects due to its O2-independence and high reactivity. However, correlational initiators for in vivo activation remain scarce. Here, we report that ultrasound excitation of oleic acid-capped BaTiO3 (OA@BaTiO3) can result in an •R cascade and hence a means to conquer hypoxic tumors. Mechanistic studies find that the •R signal disappears when OA@BaTiO3 undergoes acid washing post-treatment, which is a common procedure for removing the unwanted byproduct BaCO3. Combined with the infrared spectrum analysis, acid treatment was proven to weaken the peaks at 2840-2970 cm-1 characteristic of -CH2- and terminal -CH3 stretching vibration of OA. There is compelling evidence that high temperature thermal oxidation of OA involves the generation of •R. Thus, acid washing is considered to remove the loosely bound yet catalytically active OA. And piezoelectric BaTiO3, a potential electron-hole redox catalyst, can sensitize these OA molecules and disintegrate them to •R. This unexpected discovery provides us with a distinctive mentality to seek diverse •R initiators for tumor ablation, as well as an additional perspective on the postprocessing of synthetic materials.

Application of catalytic technology based on the piezoelectric effect in wastewater purification.

The demands of human life and industrial activities result in a significant influx of toxic contaminants into aquatic ecosystems. In particular, organic pollutants such as antibiotics and dye molecules, bacteria, and heavy metal ions are represented, posing a severe risk to the health and continued existence of living organisms. The method of removing pollutants from water bodies by utilizing the principle of the piezoelectric effect in combination with chemical catalytic processes is superior to other wastewater purification technologies because it can collect water energy, mechanical energy, etc. to achieve cleanliness and high removal efficiency. Herein, we briefly introduced the piezoelectric mechanisms and then reviewed the latest advances in the design and synthesis of piezoelectric materials, followed by a summary of applications based on the principle of piezoelectric effect to degrade pollutants in water for wastewater purification. Moreover, water purification technologies incorporating the piezoelectric effect, including piezoelectric effect-assisted membrane filtration, activation of persulfate, and battery electrocatalysis are elaborated. Finally, future challenges and research directions for the piezoelectric effect are proposed.

Ultrasound-Driven Piezoelectrocatalytic Immunoactivation of Deep Tumor.

Tumor heterogeneity makes routine drugs difficult to penetrate solid tumors, limiting their therapy efficacies. Based on high tissue penetrability of hydrogen molecules (H2 ) and ultrasound (US) and the immunomodulation effects of H2 and lactic acid (LA), this work proposes a novel strategy of US-driven piezoelectrocatalytic tumor immunoactivation for high-efficacy therapy of deep tumors by piezoelectrocatalytic hydrogen generation and LA deprivation. A kind of US-responsive piezoelectric SnS nanosheets (SSN) is developed to realize US-triggered local hydrogen production and simultaneous LA deprivation in deep tumors. The proof-of-concept experiments which are executed on an orthotopic liver cancer model have verified that intratumoral SSN-medicated piezoelectrocatalytically generated H2 liberates effector CD8+ T cells from the immunosuppression of tumor cells through down-regulating PD-L1 over-expression, and simultaneous LA deprivation activates CD8+ T cells by inhibiting regulatory T cells, efficiently co-activating tumor immunity and achieving a high outcome of liver tumor therapy with complete tumor eradication and 100% mice survival. The proposed strategy of US-driven piezoelectrocatalytic tumor immunoactivation opens a safe and efficient pathway for deep tumor therapy.

Sonocatalytic hydrogen/hole-combined therapy for anti-biofilm and infected diabetic wound healing.

It is a great challenge to effectively eradicate biofilm and cure biofilm-infected diseases because dense extracellular polymeric substance matrix prevents routine antibacterial agents from penetrating into biofilm. H2 is an emerging energy-regulating molecule possessing both high biosafety and high tissue permeability. In this work, we propose a concept of sonocatalytic hydrogen/hole-combined 'inside/outside-cooperation' anti-biofilm for promoting bacteria-infected diabetic wound healing based on two-dimensional piezoelectric nanomaterials. Proof-of-concept experiments using C3N4 nanosheets as a representative piezoelectric catalyst with wide band gap and high biosafety have verified that sonocatalytically generated H2 and holes rapidly penetrate into biofilm to inhibit bacterial energy metabolism and oxidatively deprive polysaccharides/NADH in biofilm to destroy the bacterial membrane/electron transport chain, respectively, inside/outside-cooperatively eradicating biofilm. A bacteria-infected diabetic wound model is used to confirm the excellent in vivo antibacterial performance of sonocatalytic hydrogen/hole-combined therapy, remarkably improving bacteria-infected diabetic wound healing. The proposed strategy of sonocatalytic hole/hydrogen-combined 'inside/outside-cooperation' will make a highway for treatment of deep-seated biofilm infection.

Acoustic-Activated Se Crystalline Nanodomains at Atomically-Thin Liquid-Metal Piezoelectric Heterointerfaces for Synergistic CO2 Conversion.

Acoustic-activated polarization at two-dimensional (2D) domains provide supplementary mechanisms for adjustment of empty and occupied orbitals at material heterointerfaces, activating a wide range of physicochemical applications. The piezoelectric nanodomains grown at 2D liquid-metal heterointerfaces represent a new class of polarization-dependent hybrid nanostructures with a highly challenging fabrication process. Here, the controlled growth of selenium-rich piezoelectric nanodomains on the nonpolar 2D surface of liquid Ga-based nanoparticles (NPs) enabled highly efficient and sustainable CO2 conversion. The Ga-based NPs were engulfed in carbon nanotube (CNT) frameworks. The initial hindrance effects of CNT frameworks suppressed the undesirable Ga-Se amalgamation to guarantee the suitable functions of piezocatalyst. Simultaneously, the CNT-Se mesoporous network enhances the transport and interaction of ionic species at heterointerfaces, providing unique selectivity features for CO2 conversion. Driven by acoustic energy, the multiple contributions of Ga-Se polarized heterointerfaces facilitated the piezoelectric switching and therefore increased the CO2 conversion efficiency to the value of 95.8%. The inherent compositional and functional tunability of the Ga-Se nanojunction reveal superior control over the catalyst heterointerfaces and thereby show promising potential for nanoscale applications.