Manganese Dioxide Coated Piezoelectric Nanosonosensitizer for Cancer Therapy with Tumor Microenvironment Remodeling and Multienzyme-Like Catalysis.

Sonodynamic therapy (SDT) as an emerging method for cancer therapy has encountered difficulty in insufficient production of reactive oxygen species (ROS), especially in tumor microenvironment (TME) with elevated antioxidants and hypoxic conditions. In this work, the authors have fabricated heterostructured manganese dioxide (MnO2)-coated BaTiO3 nanoparticles (BTO@M NPs) as a piezoelectric sonosensitizer, which exhibits the capacity of remodeling TME and multienzyme-like catalysis for boosting SDT. Benefitting from the piezotronic effect, the formation of a p-n junction between MnO2 and piezoelectric BTO with a built-in electric field and band bending efficiently promotes the separation of charge carriers, facilitating the generation of superoxide anion (•O2 -) and hydroxyl radical (•OH) under ultrasound (US) stimulation. Moreover, BTO@M NPs can catalyze the overexpressed hydrogen peroxide (H2O2) in TME to produce oxygen for replenishing the gas source in SDT, and also deplete antioxidant glutathione (GSH), realizing TME remodeling. During this process, the reduced Mn(II) can convert H2O2 into •OH, further amplifying cellular oxidative damage. With these combination effects, the versatile BTO@M NPs exhibit prominent cytotoxicity and tumor growth inhibition against 4T1 breast cancer. This work provides a feasible strategy for constructing high-efficiency sonosensitizers for cancer SDT.

Piezoelectric hydrogel for treatment of periodontitis through bioenergetic activation.

The impaired differentiation ability of resident cells and disordered immune microenvironment in periodontitis pose a huge challenge for bone regeneration. Herein, we construct a piezoelectric hydrogel to rescue the impaired osteogenic capability and rebuild the regenerative immune microenvironment through bioenergetic activation. Under local mechanical stress, the piezoelectric hydrogel generated piezopotential that initiates osteogenic differentiation of inflammatory periodontal ligament stem cells (PDLSCs) via modulating energy metabolism and promoting adenosine triphosphate (ATP) synthesis. Moreover, it also reshapes an anti-inflammatory and pro-regenerative niche through switching M1 macrophages to the M2 phenotype. The synergy of tilapia gelatin and piezoelectric stimulation enhances in situ regeneration in periodontal inflammatory defects of rats. These findings pave a new pathway for treating periodontitis and other immune-related bone defects through piezoelectric stimulation-enabled energy metabolism modulation and immunomodulation.

Piezoelectric Ba0.85 Sr0.15 TiO3 Nanosonosensitizer with Nitric Oxide Delivery for Boosting Cancer Therapy.

The efficacy of sonodynamic therapy (SDT) mainly relies on the sonosensitizers, which generate reactive oxygen species (ROS) upon ultrasound (US) stimulation. However, the limited availability of high-efficiency sonosensitizers hampers the therapeutic effectiveness of SDT as a standalone modality. In this work, a robust sonodynamic and gas cancer therapeutic platform is constructed based on strontium (Sr) doped barium titanate (BST) piezoelectric nanoparticles functionalized with L-arginine (BST@LA). The doping of Sr into A site of the ABO3 piezoelectric nanocrystals not only introduces oxygen vacancies into the nanoparticles and enhance the intrinsic piezoelectricity, but also narrows the semiconductor band gap and enhances charge carrier migration, all of which facilitate the sonodynamic production of superoxide anion (•O2 - ) and hydroxyl radical (•OH). In addition, the generated ROS promotes the decomposition of the surface-tethered LA, enabling the controlled release of nitric oxide (NO) gas at the tumor site, thereby achieving a combination therapeutic effect. In vivo experiments exhibit remarkable tumor suppression rate (89.5%) in 4T1 tumor mice model, demonstrating the effectiveness of this strategy. The ion doping and oxygen vacancy engineering to improve sonosensitizers, along with the synergistic combination of sonodynamic and gas therapy, provides promising avenues for improving cancer therapy.

Self-Driven Electric Field Control of Orbital Electrons in AuPd Alloy Nanoparticles for Cancer Catalytic Therapy.

The free radical generation efficiency of nanozymes in cancer therapy is crucial, but current methods fall short. Alloy nanoparticles (ANs) hold promise for improving catalytic performance due to their inherent electronic effect, but there are limited ways to modulate this effect. Here, a self-driven electric field (E) system utilizing triboelectric nanogenerator (TENG) and AuPd ANs with glucose oxidase (GOx)-like, catalase (CAT)-like, and peroxidase (POD)-like activities is presented to enhance the treatment of 4T1 breast cancer in mice. The E stimulation from TENG enhances the orbital electrons of AuPd ANs, resulting in increased CAT-like, GOx-like, and POD-like activities. Meanwhile, the catalytic cascade reaction of AuPd ANs is further amplified after catalyzing the production of H2 O2 from the GOx-like activities. This leads to 89.5% tumor inhibition after treatment. The self-driven E strategy offers a new way to enhance electronic effects and improve cascade catalytic therapeutic performance of AuPd ANs in cancer therapy.

Unconstrained Piezoelectric Vascular Electronics for Wireless Monitoring of Hemodynamics and Cardiovascular Health.

The patient-centered healthcare requires timely disease diagnosis and prognostic assessment, calling for individualized physiological monitoring. To assess the postoperative hemodynamic status of patients, implantable blood flow monitoring devices are highly expected to deliver real time, long-term, sensitive, and reliable hemodynamic signals, which can accurately reflect multiple physiological conditions. Herein, an implantable and unconstrained vascular electronic system based on a piezoelectric sensor immobilized is presented by a "growable" sheath around continuously growing arterial vessels for real-timely and wirelessly monitoring of hemodynamics. The piezoelectric sensor made of circumferentially aligned polyvinylidene fluoride nanofibers around pulsating artery can sensitively perceive mechanical signals, and the growable sheath bioinspired by the structure and function of leaf sheath has elasticity and conformal shape adaptive to the dynamically growing arterial vessels to avoid growth constriction. With this integrated and smart design, long-term, wireless, and sensitive monitoring of hemodynamics are achieved and demonstrated in rats and rabbits. It provides a simple and versatile strategy for designing implantable sensors in a less invasive way.

Bismuth nanoclusters on nitrogen-doped porous carbon nanoenzyme for cancer therapy.

Among the emerging cancer therapeutic methods, nanocatalytic therapy through the rational design of nanozymes is considered to be a promising strategy. However, high-performance nanozymes with the ability to catalyze the production of toxic substances to efficiently kill cancer cells are still highly desired. Herein, we fabricate bismuth nanoclusters loaded on nitrogen-doped porous carbon (Bi-NC) as a nanozyme for cancer therapy. The Bi-NC nanozyme displays both peroxidase (POD) and glutathione oxidase (GSHOx) biomimetic enzymatic activities, especially in a tumor microenvironment (TME), which catalyzes the production of hydroxyl radicals (·OH) and depletes antioxidant glutathione (GSH), simultaneously. Moreover, Bi-NC exhibits good photothermal conversion performance under near-infrared light irradiation. After surface modification with hyaluronic acid (HA) to improve the dispersity of nanoparticles and their accumulation in tumor tissues, Bi-NC@HA exhibits remarkable antitumor effects through the synergistic effect of catalytic and photothermal therapy. This work provides a new pathway for designing high-performance nanozymes for cancer catalytic therapy.

Covalent Organic Framework Nanocages with Enhanced Carrier Utilization and Cavitation Effect for Cancer Sonodynamic Therapy.

Ultrasound (US)-triggered sonodynamic therapy (SDT) is an emerging method for treating cancer due to its non-invasive nature and high-depth tissue penetration ability. However, current sonosensitizers commonly have unsatisfactory quantum yields of free radicals. In this work, we have developed unique organic semiconductor π-conjugated covalent organic framework nanocages (COFNs) as highly efficient sonosensitizers to boost free radical (1O2 and •OH) production and cancer therapy. With the hollow and porous structure and band transport behavior, COFNs displayed remarkably improved SDT performance through enhanced electron utilization and cavitation effect, with a 1.8-fold increase in US pressure and a 64.8% increase in 1O2 production relative to the core-shell-structured COF under US irradiation. The in vitro and in vivo experimental results verified the elevated SDT performance, showing a high tumor suppression of 91.4% against refractory breast cancer in mice. This work provides a promising strategy to develop high-performance sonosensitizers for cancer therapy.

Enhanced Sonodynamic Cancer Therapy through Iron-Doping and Oxygen-Vacancy Engineering of Piezoelectric Bismuth Tungstate Nanosheets.

Sonodynamic therapy (SDT) is regarded as a new-rising strategy for cancer treatment with low invasiveness and high tissue penetration, but the scarcity of high-efficiency sonosensitizers has seriously hindered its application. Herein, the iron-doped and oxygen-deficient bismuth tungstate nanosheets (BWO-Fe NSs) with piezotronic effect are synthesized for enhanced SDT. Due to the existence of oxygen defects introduced through Fe doping, the bandgap of BWO-Fe is significantly narrowed so that BWO-Fe can be more easily activated by exogenous ultrasound (US). The oxygen defects acting as the electron traps inhibit the recombination of US-induced electrons and holes. More importantly, the dynamically renewed piezoelectric potential facilitates the migration of electrons and holes to opposite side and causes energy band bending, which further promotes the production of reactive oxygen species. Furthermore, Fe doping endows BWO-Fe with Fenton reactivity, which converts hydrogen peroxide (H2 O2 ) in tumor microenvironment into hydroxyl radicals (•OH), thereby amplifying the cellular oxidative damage and enhancing SDT. Both in vitro and in vivo experiments illustrate their high cytotoxicity and tumor suppression rate against refractory breast cancer in mice. This work may provide an alternative strategy to develop oxygen-deficient piezoelectric sonosensitizers for enhanced SDT via doping metal ions.

Manganese oxide-modified bismuth oxychloride piezoelectric nanoplatform with multiple enzyme-like activities for cancer sonodynamic therapy.

Sonodynamic therapy (SDT) is considered as a new-rising strategy for cancer therapeutics, but the inefficient production of reactive oxygen species (ROS) by current sonosensitizers seriously hinders its further applications. Herein, a piezoelectric nanoplatform is fabricated for enhancing SDT against cancer, in which manganese oxide (MnOx) with multiple enzyme-like activities is loaded on the surface of piezoelectric bismuth oxychloride nanosheets (BiOCl NSs) to form a heterojunction. When exposed to ultrasound (US) irradiation, piezotronic effect can remarkably promote the separation and transport of US-induced free charges, and further enhance ROS generation in SDT. Meanwhile, the nanoplatform shows multiple enzyme-like activities from MnOx, which can not only downregulate the intracellular glutathione (GSH) level, but also disintegrate endogenous hydrogen peroxide (H2O2) to generate oxygen (O2) and hydroxyl radicals (•OH). As a result, the anticancer nanoplatform substantially boosts ROS generation and reverses tumor hypoxia. Ultimately, it reveals remarkable biocompatibility and tumor suppression in a murine model of 4 T1 breast cancer under US irradiation. This work provides a feasible pathway for improving SDT using piezoelectric platforms.

Self-Driven Electrical Stimulation-Promoted Cancer Catalytic Therapy and Chemotherapy Based on an Implantable Nanofibrous Patch.

The efficacy of cancer catalytic therapy is still hindered by the inefficient generation of reactive oxygen species (ROS). Herein, we report a self-driven electrical stimulation-promoted cancer catalytic therapy and chemotherapy by integrating a human-driven triboelectric nanogenerator (TENG) with an implantable and biodegradable nanofibrous patch. The gelatin/polycaprolactone nanofibrous patch incorporates doxorubicin (DOX) and graphitic carbon nitride (g-C3N4), in which the peroxidase (POD)-like activity of g-C3N4 to produce hydroxyl radical (•OH) can be distinctly enhanced by the self-driven electrical stimulation for 4.12-fold, and simultaneously DOX can be released to synergize the therapy, especially under a weakly acidic tumor microenvironment (TME) condition. The in vitro and in vivo experimental results on a mouse breast cancer model demonstrate superior tumor suppression outcome. The self-powered electrical stimulation-enhanced catalytic therapy and chemotherapy via multifunctional nanofibrous patches proposes a new complementary strategy for the catalytic therapy of solid tumors.

Acid etching followed by hydrothermal preparation of nanosized Bi2O4/Bi2O3 p-n junction as highly efficient visible-light photocatalyst for organic pollutants removal.

As a promising visible-light photocatalyst, Bi2O4 has the advantage of broadband spectral response range. However, the high recombination rate of photoexcited charge carriers induced by the submicrorod morphology of pure Bi2O4 greatly restricts its visible-light photocatalytic performance. Herein, a novel nanosized Bi2O4/Bi2O3 p-n junction was developed by a dilute HCl acid etching and subsequent hydrothermal method, using NaBiO3·2H2O as the sole bismuth precursor. A product of NaBiO3·2H2O@BiOCl was formed firstly when NaBiO3·2H2O was partially reduced by insufficient dilute HCl aqueous solution. Then, BiOCl reacted with NaBiO3·2H2O during the following hydrothermal reaction process, resulting in the formation of Bi2O4 nanoparticles (NPs) anchored on the surface of plate-like Bi2O3. The content of Bi2O3 in the junction can be easily controlled by changing the added amount of dilute HCl acid. This strategy could not only realize the NPs-sized Bi2O4 but also construct nanometered Bi2O4/Bi2O3 p-n junction simultaneously, which remarkably improves the separation efficiency of charge carriers. Furthermore, the obtained Bi2O4/Bi2O3 heterojunctions have larger specific surface areas than Bi2O4 alone. Due to these advantages, the photocatalytic removal rate of methyl orange (MO) and phenol for the optimal Bi2O4/Bi2O3 heterostructure increased respectively by 5.06 and 2.16 times under visible light, when compared with single Bi2O4. The results of active species trapping experiment and electron spin resonance (ESR) spectra indicate that holes (h+) and superoxide radicals (O2-) are the primary and secondary reactive active species during the photocatalytic degradation process, respectively. This work provides a novel perspective for the design and preparation of high performance Bi2O4-based photocatalyst.

TiO2-graphene composites with exposed {001} facets produced by a one-pot solvothermal approach for high performance photocatalyst.

TiO2-graphene (TOG) composites with exposed TiO2 {001} facets were prepared by a solvothermal approach without any addition of surfactants or capping agents, only using titanium isopropoxide and graphene oxide ethanol suspension as the precursors. Graphene was covered uniformly and densely with anatase TiO2 nanoparticles, exposing the {001} facets. The X-ray photoelectron spectroscopy, photoluminescence spectroscopy and photocurrent measurements show the presence of electron transfer between TiO2 and graphene. The electron transfer between TiO2 and graphene will greatly retard the recombination of photoinduced charge carriers and prolong electron lifetime, which will contribute to the enhancement of photocatalytic performance. Accordingly, the TOG composites show high photocatalytic activity of methyl orange under UV light, likely due to the effective separation of photoinduced charge, exposure of highly reactive {001} facets and great adsorptivity of dyes.