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Ultrasound (US) generates toxic reactive oxygen species (ROS) by acting on sonosensitizers for cancer treatment, and the mechanical damage induced by cavitation effects under US is equally significant. Therefore, designing a novel sonosensitizer that simultaneously possesses efficient ROS generation and enhanced mechanical effects is promising. In this study, carbon-doped zinc oxide nanoparticles (C-ZnO) are constructed for mechano-sonodynamic cancer therapy. The presence of carbon (C) doping optimizes the electronic structure, thereby enhancing the ROS generation triggered by US, efficiently inducing tumor cell death. On the other hand, the high specific surface area and porous structure brought about by C doping enable C-ZnO to enhance the mechanical stress induced by cavitation bubbles under US irradiation, causing severe mechanical damage to tumor cells. Under the dual effects of sonodynamic therapy (SDT) and mechanical therapy mediated by C-ZnO, excellent anti-tumor efficacy is demonstrated both in vitro and in vivo, along with a high level of biological safety. This is the first instance of utilizing an inorganic nanomaterial to achieve simultaneous enhancement of ROS production and US-induced mechanical effects for cancer therapy. This holds significant importance for the future development of novel sonosensitizers and advancing the applications of US in cancer treatment., (© 2024 Wiley‐VCH GmbH.)

Neurological diseases are a major global health challenge, affecting hundreds of millions of people worldwide. Ultrasound therapy plays an irreplaceable role in the treatment of neurological diseases due to its noninvasive, highly focused, and strong tissue penetration capabilities. However, the complexity of brain and nervous system and the safety risks associated with prolonged exposure to ultrasound therapy severely limit the applicability of ultrasound therapy. Ultrasound-sensitive intelligent nanosystems (USINs) are a novel therapeutic strategy for neurological diseases that bring greater spatiotemporal controllability and improve safety to overcome these challenges. This review provides a detailed overview of therapeutic strategies and clinical advances of ultrasound in neurological diseases, focusing on the potential of USINs-based ultrasound in the treatment of neurological diseases. Based on the physical and chemical effects induced by ultrasound, rational design of USINs is a prerequisite for improving the efficacy of ultrasound therapy. Recent developments of ultrasound-sensitive nanocarriers and nanoagents are systemically reviewed. Finally, the challenges and developing prospects of USINs are discussed in depth, with a view to providing useful insights and guidance for efficient ultrasound treatment of neurological diseases., (© 2023 Wiley‐VCH GmbH.)

Sonodynamic therapy (SDT) has been widely reported as a noninvasive and high-penetration therapy for cancer; however, the design of an efficient sonosensitizer remains an urgent need. To address this issue, molybdenum disulfide nanoflowers (MoS 2 NF) as piezo-sonosensitizers and introduced sulfur vacancies on the MoS 2 NF (Sv-MoS 2 NF) to improve their piezoelectric property for cancer therapy are designed. Under ultrasonic mechanical stress, the Sv-MoS 2 NF resulted in piezoelectric polarization and band tilting, which enhanced the charge carrier separation and migration. This resulted in an improved catalytic reaction for reactive oxygen species (ROS) production, ultimately enhancing the SDT performance. Thanks to the high efficiency of ROS generation, the Sv-MoS 2 NF have demonstrated a good anticancer effect in vitro and in vivo. Following a systematic evaluation, Sv-MoS 2 NF also demonstrated good biocompatibility. This novel piezo-sonosensitizer and vacancy engineering strategy provides a promising new approach for achieving efficient SDT., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Sonodynamic therapy (SDT) is a non-invasive and highly penetrating treatment strategy under ultrasound irradiation. However, uncertainty in the mechanism of SDT has seriously hindered its future clinical application. Here, the mechanism of SDT enhanced by the wettability of nanoparticles is investigated. Nanoparticles can adsorb and stabilize nanobubbles in liquid, thus enhancing SDT efficiency. The stability of the nanobubbles is positively correlated with the desorption energy of the nanoparticles, which is determined by the wettability of the nanoparticles. This conclusion is verified for mesoporous silica and polystyrene nanoparticles and it is found that nanoparticles with a water contact angle of about 90° possess the largest desorption energy. To further apply this conclusion, thrombus models are constructed on rats and the experimental results demonstrate that nanoparticles with the largest desorption energy have the highest thrombolytic efficiency. It is believed that these findings will help to better understand the SDT mechanism and guide new strategies for rational design of nanoparticles adopted in SDT., (© 2021 Wiley-VCH GmbH.)

Metal-organic frameworks (MOFs)-based yolk-shell nanostructures have drawn enormous attention recently due to their multifunctionality. However, the regulations of the size and morphology of yolk-shell nanostructures are still limited by the unclear formation mechanism. Herein, we first demonstrated a solvent-dependent adsorption-driven mechanism for synthesizing yolk-shelled MOFs-based nanostructures coated with mesoporous SiO 2 shells (ZIF-8@mSiO 2 ) with tunable size and morphology. The selective and competitive adsorption of methanol (CH 3 OH) and water (H 2 O) on ZIF-8 core were found to have decisive effects on inducing the morphology evolution of yolk-shell nanostructures. The obtained yolk-shelled ZIF-8@mSiO 2 nanostructures show great promise in generating acoustic cavitation effect for sonodynamic cancer therapy in vitro. We believe that this work will not only help us to design novel MOFs-based yolk-shell nanostructures, but also promote the widespread application of MOFs materials., (© 2021 Wiley-VCH GmbH.)

The high reactive oxygen species (ROS) generation ability and simple construction of sonosensitizer systems remain challenging in sonodynamic therapy against the hypoxic tumor. In this work, we rationally prepared MOF-derived double-layer hollow manganese silicate nanoparticle (DHMS) with highly effective ROS yield under ultrasound irradiation for multimodal imaging-guided sonodynamic therapy (SDT). The presence of Mn in DHMS increased ROS generation efficiency because it could be oxidized by holes to improve the electron-hole separation. Moreover, DHMS could produce oxygen in the tumor microenvironment, which helps overcome the hypoxia of the solid tumor and thus enhance the treatment efficiency. In vivo experiments demonstrated efficient tumor inhibition in DHMS-mediated SDT guided by ultrasound and magnetic resonance imaging. This work presents a MOF-derived nanoparticle with sonosensitive and oxygen generating ability, which provides a promising strategy for tumor hypoxia in SDT., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Chemo-phototherapy, as a promising cancer combination therapy strategy, has attracted widespread attention. However, the complex tumor microenvironment restricts the penetration depth of chemo-phototherapy agents in the tumor region. Here, biodegradable amphiphilic gelatin (AG) wrapped nanocomposite (PRDCuS@AG) composed of doxorubicin and copper sulfide (CuS)-loaded dendrimer is designed for deep tumor chemo-phototherapy. PR in PRDCuS@AG represents arginine-conjugated polyamidoamine dendrimer. PRDCuS@AG can rapidly biodegrade into PRDCuS by matrix metalloproteinases under near-infrared light irradiation. The resulted PRDCuS harbors dual cell-tissue penetration ability, which can effectively penetrate deep into the tumor tissue. In particular, PRDCuS@AG achieves photoacoustic imaging-guided synergistic chemo-phototherapy with 97% of tumor inhibition rate. Moreover, PRDCuS@AG can further degrade into 3 nm ultrasmall CuS, which can be eliminated from the body after treatment to avoid side effects. This strategy provides an insight that the development of chemo-phototherapy agents with high penetration ability to overcome the limitation of current deep tumor therapy., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Two-dimensional (2D) nanomaterials are currently explored as novel photothermal agents because of their ultrathin structure, high specific surface area, and unique optoelectronic properties. In addition to single photothermal therapy (PTT), 2D nanomaterials have demonstrated significant potential in PTT-based synergistic therapies. In this Minireview, we summarize the recent progress in 2D nanomaterials for enhanced photothermal cancer therapy over the last five years. Their unique optical properties, typical synthesis methods, and surface modification are also covered. Emphasis is placed on their PTT and PTT-synergized chemotherapy, photodynamic therapy, and immunotherapy. The major challenges of 2D photothermal agents are addressed and the promising prospects are also presented., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Enzymes have been used to direct the conversion of prodrugs in cancer therapy. However, non-specific distribution of endogenous enzymes seriously hinders their bioapplications. Herein, we developed a near-infrared-triggered locoregional chemo-photothermal therapy based on the exogenous enzyme delivery and remolded tumor mivroenvironment. The catalytic efficiency of enzymes was enhanced by the hyperthermia, and the therapeutic efficacy of photothermal therapy (PTT) was improved owing to the inhibition of heat shock protein 90 by chemotherapeutics. The locoregional chemo-phototherapy achieved a one-time successful cure in 4T1 tumor-bearing mice model. Thus, a mutually reinforcing feedback loop between PTT and chemotherapy can be initiated by the irradiation, which holds a promising future in cancer therapy., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Single-atom catalysts (SACs), as homogeneous catalysts, have been widely explored for chemical catalysis. However, few studies focus on the applications of SACs in enzymatic catalysis. Herein, we report that a zinc-based zeolitic-imidazolate-framework (ZIF-8)-derived carbon nanomaterial containing atomically dispersed zinc atoms can serve as a highly efficient single-atom peroxidase mimic. To reveal its structure-activity relationship, the structural evolution of the single-atom nanozyme (SAzyme) was systematically investigated. Furthermore, the coordinatively unsaturated active zinc sites and catalytic mechanism of the SAzyme are disclosed using density functional theory (DFT) calculations. The SAzyme, with high therapeutic effect and biosafety, shows great promises for wound antibacterial applications., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Photothermal-radiotherapy (PT-RT) is an effective strategy for relieving hypoxia-related radiotherapy resistance and inducing tumor-specific cell apoptosis/necrosis. Nevertheless, limited tissue penetration of near-infrared (NIR) laser and the serious side effects of high-dose radiation severely hinder its applications for deep tumors. An interventional photothermal-brachytherapy (IPT-BT) technology is proposed here for the internal site-specific treatment of deep tumors. This technology utilizes a kind of biodegradable honeycomb-like gold nanoparticles (HGNs) acting as both internal photothermal agents and radiosensitizers. A high tumor inhibition rate of 96.6% is achieved in SW1990 orthotopic pancreatic tumor-bearing mice by HGNs-mediated IPT-BT synergistic therapy. Interestingly, this approach effectively causes double-stranded DNA damage and improves the oxygen supply and the penetration of nanoparticles inside the tumor. Therefore, it is believed that this strategy may open up a new avenue for PT-RT synergistic therapy of deep malignant tumors and has a significant impact on the future clinical translation., Competing Interests: The authors declare no conflict of interest.

Loading novel metal nanosheets onto nanosheet support can improve their catalytic performance, but the morphological incompatibility makes it difficult to construct a well-contacted interface, which is of particular interest in supported catalysts. Herein, Pd nanosheets (Pd NSs) are supported onto graphitic carbon nitride nanosheets (CNNSs) with intimate face-to-face contact through an in situ growth method. This method overcomes the limitations of the morphological incompatibility and ensures the intimate interfacial contact between Pd NSs and CNNSs. The nitrogen-rich nature of CNNSs endows Pd NSs with abundant anchoring sites, which optimizes the electronic structure and improves the chemical and morphological stability of Pd NSs. The supported Pd NSs demonstrate high dispersion and exhibit largely enhanced activity toward the reduction of 4-nitrophenol. The concentration-normalized rate constant is up to 3052 min -1 g -1 L, which is 5.4 times higher than that obtained by unsupported Pd NSs. No obvious deactivation is observed after six runs of the recycling experiments. It is believed that the supported novel metal nanosheets with the intimately contacted interface may show promising applications in catalysis., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Sonodynamic therapy (SDT) can overcome the critical issue of depth-penetration barrier of photo-triggered therapeutic modalities. However, the discovery of sonosensitizers with high sonosensitization efficacy and good stability is still a significant challenge. In this study, the great potential of a metal-organic-framework (MOF)-derived carbon nanostructure that contains porphyrin-like metal centers (PMCS) to act as an excellent sonosensitizer is identified. Excitingly, the superior sonosensitization effect of PMCS is believed to be closely linked to the porphyrin-like macrocycle in MOF-derived nanostructure in comparison to amorphous carbon nanospheres, due to their large highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gap for high reactive oxygen species (ROS) production. The nanoparticle-assisted cavitation process, including the visualized formation of the cavitation bubbles and microjets, is also first captured by high-speed camera. High ROS production in PMCS under ultrasound is validated by electron spin resonance and dye measurement, followed by cellular destruction and high tumor inhibition efficiency (85%). This knowledge is important from the perspective of understanding the structure-dependent SDT enhancement of a MOF-derived carbon nanostructure., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)