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ULTRASOUND IN MEDICINE AND BIOLOGY · 2025 · IF 2.6

Effects of Ultrasonic Irradiation and pH on the Enzymatic Activity and Biological Properties of Cerium Oxide Nanoparticles

Wendi Su,Hao Wang,Juhong Pan,Huan Pu,Bin Gui,Qianhui Liu,Sheng Cao,Qing Zhou

Objective Cerium oxide nanoparticles (CeO 2 NPs), as metal oxide nanomaterials with multi-enzyme activities, are gradually being applied in the biomedical field. However, we have limited knowledge about the factors influencing the enzymatic activity and biological functions of cerium oxide nanoparticles. This study aims to investigate whether ultrasonic irradiation has a significant impact on their enzymatic activity, reactive oxygen species scavenging ability, and antibacterial activity, and to discuss the underlying mechanisms of these effects. Methods We first synthesized cerium oxide nanoparticles using a chemical precipitation method and characterized them. We set up a control group and irradiation groups with different ultrasonic parameters, and tested the mimicking activities of catalase, superoxide dismutase, and peroxidase of the cerium oxide nanoparticles using enzymatic activity assay kits. Then, we assessed the biocompatibility of the cerium oxide nanoparticles in macrophages. Subsequently, we examined their reactive oxygen species scavenging ability in both tumor cells and macrophages. Finally, we tested their inhibitory effect on Staphylococcus aureus . Results We found that cerium oxide nanoparticles exhibited enhanced enzymatic activity after ultrasound irradiation. The direction of their catalysis was regulated by pH: in environments with lower pH values, the peroxidase activity of the cerium oxide nanoparticles was stronger than that of catalase and superoxide dismutase, whereas in environments with higher pH values, the opposite was true. This pH-regulated multienzymatic activity resulted in significantly different reactive oxygen species (ROS) scavenging abilities between acidic tumor cells and slightly alkaline normal tissue cells: it demonstrated excellent ROS scavenging ability in macrophages but showed no ROS scavenging ability in tumor cells. Lastly, we discovered that the nanoparticles exhibited stronger antibacterial capabilities after ultrasound irradiation. Conclusion Ultrasound can enhance the enzymatic activity, ROS scavenging ability, and antibacterial capability of cerium oxide nanoparticles.

CAS / MDL: 10294-41-4 1310-73-2
研究领域: 纳米技术 · 生物医学工程 · 酶学 · 微生物学 · 材料科学
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JOURNAL OF ELECTRONIC MATERIALS · 2025 · IF 2.5

Synthesis of NiTiO3/TiO2 Composite Nanoparticles by a Green Approach: Application as Sonocatalyst for Dye Degradation

Khoa Vu Dang,Bac Luong Huu

A novel NiTiO 3 /TiO 2 heterostructure was synthesized via a green sol–gel method using lemon juice as a natural precursor. The phase formation, structural, morphological, and optical properties of the synthesized composite were investigated using x-ray diffraction (XRD), Raman scattering, field-emission scanning electron microscopy (FESEM), and diffuse reflectance spectroscopy. XRD and Raman scattering results confirm the coexistence of both ilmenite NiTiO 3 and TiO 2 phases in the composite. The TiO 2 phase in the composite undergoes temperature-dependent phase transformation: it exists as anatase when calcined at 600°C, a mixture of anatase and rutile at 700°C, and pure rutile at 800°C. FESEM reveals that the synthesized NiTiO 3 particles exhibit spherical nanostructures. The NiTiO 3 /TiO 2 composites were investigated for their sonocatalytic activity in the degradation of rhodamine B under ultrasonic irradiation. The composite exhibited significantly enhanced sonocatalytic performance compared to pure NiTiO 3 , which can be attributed to the improved interfacial charge transfer and the synergistic effects between NiTiO 3 and TiO 2 . These results highlight the potential of green-processed composites in advanced oxidation processes for wastewater treatment. Graphic abstract

CAS / MDL: 7550-45-0
研究领域: 材料科学 · 环境工程 · 纳米技术 · 催化 · 绿色化学
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Small · 2021 ·Vol. 18 ·期 9 ·2104550 · IF 13.281

Oxygen-Deficient BiOCl Combined with L-Buthionine-Sulfoximine Synergistically Suppresses Tumor Growth through Enhanced Singlet Oxygen Generation under Ultrasound Irradiation

Hui Wang,Weitao Yang,Kexin Bian,Weiwei Zeng,Xiao Jin,Ruizhuo Ouyang,Yan Xu,Chenyu Dai,Shuang Zhou,Bingbo Zhang

Excess generation of reactive oxygen species (ROS) based on sensitizers under ultrasound (US) excitation can cause the death of tumor cells via oxidative damage, but sonosensitizers are largely unexplored. Herein, oxygen-deficient black BiOCl (B-BiOCl) nanoplates (NPs) are reported, with post-treatment on conventional BiOCl by simple UV excitation, showing stronger singlet oxygen ( 1 O 2 ) generation than commercial TiO 2 nanoparticles and their derivatives under US irradiation. Moreover, L-buthionine-sulfoximine (BSO), a GSH biosynthesis inhibitor, is incorporated into B-BiOCl NPs. The authors find that BSO can be released owing to the degradation of B-BiOCl NPs in the presence of acid and GSH, which are overexpressed in tumors. The results show that BSO/B-BiOCl-PEG NPs have a multifunctional synergistic effect on improving ROS production. In particular, BiOCl has remarkable near-infrared light absorption after UV treatment and is good for photoacoustic imaging that can guide subsequent sonodynamic therapy. This work shows that just with a simple oxygen deficiency treatment, strong 1 O 2 generation can be provided to a conventional material under US irradiation and, interestingly, this effect can be amplified by using a small inhibitor BSO, and this is clearly demonstrated in cell and mice experiments.

研究领域: 癌症治疗 · 材料科学 · 生物医学工程 · 纳米技术 · 药学
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JOURNAL OF ALLOYS AND COMPOUNDS · 2023 · IF 6.2

Synthesis and sonodynamic performance of spinel ferrites

Qin Jiang,Zijun Zhao,Wen Zhang,Haiyan Zeng,Hanhan Lv,Zixiao Liu,Zhigang Chen

Sonodynamic therapy has emerged as one of the most valuable treatment methods with low side effects and deep tissue penetration. As a representative inorganic sonosensitizer, spinel-type ferrites have many advantages such as high reactive oxygen species (ROS) production efficiency and stability. However, current studies have not explored how metal doping impacts the sonodynamic effect of spinel ferrites. Herein, we synthesized three kinds of spinel ferrite nanoparticles (ZnFe 2 O 4 , CoFe 2 O 4 , and MgFe 2 O 4 ) and systematically investigated their sonodynamic performance. It is shown that three spinel ferrites are capable of producing singlet oxygen under ultrasound irradiation. Hydrogen peroxide further enhances the production of singlet oxygen, increasing the production rate by 1.05–2.31 times. The simultaneous existence of Co 2+ /Co 3+ and Fe 2+ /Fe 3+ redox couples in CoFe 2 O 4 could convert more efficiently hydrogen peroxide into oxygen through catalytic reaction, providing more oxygen to promote singlet oxygen production. Thus, CoFe 2 O 4 exhibits higher production efficiency than ZnFe 2 O 4 and MgFe 2 O 4 . In vitro experiments demonstrate the good biocompatibility of CoFe 2 O 4 nanoparticles and high ability to effectively kill cancer cells under ultrasound irradiation. In addition, CoFe 2 O 4 shows good therapeutic efficacy in animal models of colon cancer. These findings highlight the great potential of ferrite sonosensitizer for cancer treatment.

CAS / MDL: 7791-13-1
研究领域: 纳米技术 · 材料科学 · 癌症治疗 · 生物医学工程
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BIOMATERIALS · 2022 · IF 15.304

Engineering dual catalytic nanomedicine for autophagy-augmented and ferroptosis-involved cancer nanotherapy

Zhifang Li,Chunmei Wang,Chen Dai,Ruizhi Hu,Li Ding,Wei Feng,Hui Huang,Yin Wang,Jianwen Bai,Yu Chen

Chemodynamic therapy represents a distinct anti-tumor strategy by activating intratumoral chemical catalytic reactions to produce highly toxic reactive oxygen species (ROS) from non-/limited-toxic nanocatalysts . However, the low efficacy of ROS generation still remains a major challenge for further clinical translation. Herein, a liposomal nanosystem which simultaneously encapsulated copper peroxide nanodots (CPNs) and artemisinin (ART) was constructed for autophagy-enhanced and ferroptosis-involved cancer cell death owing to Cu-based dual catalytic strategy. To be specific, the CPN components, served as a H 2 O 2 self-supplying platform, release H 2 O 2 and Cu 2+ under acidic tumor environment and endogenously generate . OH via Fenton-like reaction (catalytic reaction I). In addition, Cu 2+ species catalyze ART components to produce ROS radicals (catalytic reaction II), further augmenting the intracellular oxidative damage and lipid peroxide accumulation, leading to cancer cell death. Specifically, ART also acted as a potent autophagy inducer increasing the level of intracellular iron pool through degradation of ferritin , which could promote cancer cell ferroptosis , producing the best antineoplastic effect. After accumulation into the tumor sites, ultrasound irradiation was applied to trigger the release of CPNs and ART from liposomal nanosystems, and amplify the efficacy of catalytic reaction for maximum therapeutic effect. Both in vitro and in vivo therapeutic outcomes suggest the outstanding autophagy-augmented ferroptosis-involved cancer-therapeutic efficacy, which was further corroborated by transcriptome sequencing. In this work, Cu was firstly proven to trigger ART to produce ROS species, but also provide a TME-responsive nanoplatform for potentially suppressing tumor growth by autophagy-augmented ferroptosis-involved cancer nanotherapy.

研究领域: 纳米医学 · 癌症治疗 · 生物医学工程 · 药学
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International Journal of Nanomedicine · 2024 · IF 6.6

Bioactive Nanoliposomes for Enhanced Sonodynamic-Triggered Disulfidptosis-Like Cancer Cell Death via Lipid Peroxidation

Hongwei Xiang,Bin Shen,Chunmei Zhang,Rui Li

Introduction Cell death regulation holds a unique value in the field of cancer therapy. Recently, disulfidptosis has garnered substantial scientific attention. Previous studies have reported that sonodynamic therapy (SDT) based on reactive oxygen species (ROS) can regulate cancer cell death, achieving an limited anti-cancer effect. However, the integration of SDT with disulfidptosis as an anti-cancer strategy has not been extensively developed. In this study, we constructed an artificial membrane disulfidptosis sonosensitizer, specifically, a nanoliposome (SC@lip) coated with a combination of the chemotherapy medicine Sorafenib (Sora) and sonosensitizer Chlorin e6 (Ce6), to realize a one-stop enhanced SDT effect that induces disulfidptosis-like cancer cell death.Methods Sorafenib and Ce6 were co-encapsulated into PEG-modified liposomes, and SC@Lip was constructed using a simple rotary evaporation phacoemulsification method. The cell phagocytosis, ROS generation ability, glutathione (GSH) depletion ability, lipid peroxidation (LPO), and disulfidptosis-like death mediated by SC@Lip under ultrasound (US) irradiation were evaluated. Based on a 4T1 subcutaneous tumor model, both the in vivo biological safety assessment and the efficacy of SDT were assessed.Results SC@Lip exhibits high efficiency in cellular phagocytosis. After being endocytosed by 4T1 cells, abundant ROS were produced under SDT activation, and the cell survival rates were below 5%. When applied to a 4T1 subcutaneous tumor model, the enhanced SDT mediated by SC@Lip inhibited tumor growth and prolonged the survival time of mice. In vitro and in vivo experiments show that SC@Lip can enhance the SDT effect and trigger disulfidptosis-like cancer cell death, thus achieving anti-tumor efficacy both in vitro and in vivo.Conclusion SC@Lip is a multifunctional nanoplatform with an artificial membrane, which can integrate the functions of sonosensitization and GSH depletion into a biocompatible nanoplatform, and can be used to enhance the SDT effect and promote disulfidptosis-like cancer cell death.

研究领域: 癌症治疗 · 纳米技术 · 细胞生物学 · 药学 · 生物医学工程
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Facile Synthesis of a Multifunctional Porous Organic Polymer Nanosonosensitizer (mHM@HMME) for Enhanced Cancer Sonodynamic Therapy

Meiting Li,Zhuoyin Liu,Junjie Tang,LiLi Cheng,Yifan Xue,Yadong Liu,Jie Liu

Sonodynamic therapy (SDT), which involves the activation of sonosensitizers to generate cytotoxic reactive oxygen species under ultrasound irradiation, is a promising noninvasive modality for cancer treatment. However, the clinical translational application of SDT is impeded by the lack of efficient sonosensitizers, the inefficient accumulation of sonosensitizers at tumor sites, and the complicated immunosuppressive tumor microenvironment. Herein, we developed a facilely synthesized multifunctional porous organic polymer nanosonosensitizer (mHM@HMME) for enhanced SDT. Specifically, mHM@HMME nanosonosensitizers were prepared by incorporating chemotherapeutic mitoxantrone into the one-step synthesis process of disulfide bond containing porous organic polymers, followed by loading with organic sonosensitizer (HMME) and camouflaging with a cancer cell membrane. Due to the cancer cell membrane camouflage, this multifunctional mHM@HMME nanosonosensitizer showed prolonged blood circulation and tumor targeting aggregation. Under ultrasound irradiation, the mHM@HMME nanosonosensitizer exhibited a satisfactory SDT performance both in vitro and in vivo. Moreover, the potent SDT combined with glutathione-responsive drug release in tumor cells induced robust immunogenic cell death to enhance the antitumor effect of SDT in turn. Overall, this facilely synthesized multifunctional mHM@HMME nanosonosensitizer shows great potential application in enhanced SDT.

研究领域: 癌症研究 · 纳米技术 · 治疗学 · 材料科学 · 生物医学工程
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Nature Communications · 2024 ·Vol. 15 ·期 1 ·1-19 · IF 14.7

γ-Glutamyl transpeptidase-activable nanoprobe crosses the blood-brain barrier for immuno-sonodynamic therapy of glioma

Li Bo,Chen Gengjia,Zhong Huihai,Li Tan,Lin Minzhao,Wei Huiye,Zhang Qiaoyun,Chen Qi,Huang Jinsheng,Shuai Xintao

Effective treatment against glioma remains challenging nowadays because the protective blood-brain barrier (BBB) impedes drug penetration into brain and the limited efficacy of conventional chemotherapy. While strong positively charged nanoparticles have good permeability through the BBB, they often come with the caveat of cationic toxicity to healthy tissues and organs during blood circulation. Here we show a neutrally charged nanoprobe with a surface decorated with γ -glutamyl moieties that can be cleaved by γ -glutamyl transpeptidase, an enzyme overexpressed on brain capillaries. Upon the cleavage, positively charged primary amines are generated, facilitating the effective crossing of the nanoprobe through BBB via the adsorption-mediated transcytosis pathway, while avoiding the caveat of cationic toxicity. In addition, when reaching the acidic tumor microenvironment, the nanoprobe co-encapsulating sonosensitizer and immune agonist swells, which results in an accelerated drug release under ultrasound irradiation to induce a combined immune response, ultimately leading to a robust anticancer effect. Overall, we report an effective drug delivery nanoplatform across the BBB for an enhanced therapy of glioma.

研究领域: 纳米技术 · 神经肿瘤学 · 药理学 · 诊疗学
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

Boosting the tumor photothermal therapy with hollow CoSnSx-based injectable hydrogel via the sonodynamic and dual-gas therapy

Lu Jia,Yuzhu Wang,Tingting Hu,Chunyu Yang,Huiming Lin,Feng Zhang,Fengyu Qu,Liru Cui,Wei Guo

Photothermal therapy (PTT) has attracted considerable attention in the field of nanomedicine owing to its high efficiency, low invasiveness , and precise controllability. However, limited by the activation of the immune system by PTT and the low penetrating ability of near-infrared lasers, the use of a single PTT is usually ineffective. Herein, a unique injectable hydrogel system was strategically designed and fabricated using CoSnS x , L-arginine, chitosan (CTS), and carboxymethyl cellulose (CMC) for sonodynamic and dual-gas therapy cooperative PTT. CoSnS x with a hollow structure can not only produce a large amount of singlet oxygen ( 1 O 2 ) under ultrasonic (US) irradiation, but also produce H 2 S gas in an acidic environment, so as to achieve sonodynamic and gas therapeutic effects. Additionally, CoSnS x exhibited excellent photothermal conversion efficiency of 48.24% under 808 nm laser irradiation. As a precursor of NO, L-arginine is incorporated into the hydrogel to enable the controlled release of NO under US/laser irradiation, thereby enhancing the PTT effect. Such a multifunctional injectable hydrogel system can achieve high therapeutic efficacy through sonodynamic and dual-gas treatment-enhanced PTT, as demonstrated by both in vitro and in vivo experiments. Our designed injectable hydrogel system provides a unique solution for enhancing the PTT.

研究领域: 纳米医学 · 癌症治疗 · 生物医学工程
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2023 · IF 9.9

Multifunctional nanoplatform based on tetragonal BaTiO3-Au@polydopamine for computed tomography imaging-guided photothermal synergistic and enhanced piezocatalytic cancer therapy

Qi Xu,Gong Chen,Han Hu,Zhimin Mo,Wenqiu Chen,Qianyuan He,Zushun Xu,Xiaofang Dai

Non-centrosymmetric tetragonal barium titanate nanocrystals have the potential to serve as piezoelectric catalysts in cancer therapy. When exposed to ultrasound irradiation, BaTiO 3 can generate reactive oxygen species with a noninvasive and deep tissue-penetrating approach. However, the application of BaTiO 3 in cancer nanomedicine is limited by their biosafety, biocompatibility, and dosage efficiency. To explore the potential application of BaTiO 3 in nanomedical cancer treatment, we introduced ultra-small Au nanoparticles onto the surface of BaTiO 3 to enhance the piezoelectric catalytic performance. Additionally, we also coated the BaTiO 3 with polydopamine to improve their biosafety and biocompatibility. This led to the preparation of a novel multifunctional BaTiO 3 -based nanoplatform called BTAPs. In vitro and in vivo experiments demonstrated that the incorporation of Au dopants and polydopamine coating successfully improved the piezoelectric catalysis properties and biocompatibility of BaTiO 3 . Compared with unmodified BaTiO 3 , BTAPs achieved a similar piezoelectric catalytic effect at a low dose (0.3 mg ml −1 in vitro and 10 mg kg −1 in vivo ). Moreover, BTAPs also exhibited enhanced properties in computed tomography imaging and photothermal effects in vivo . Therefore, BTAPs offer valuable insights into the advantages and limitations of piezoelectric catalytic nanomedicine in cancer treatment.

CAS / MDL: 62-31-7
研究领域: 纳米医学 · 癌症治疗 · 材料科学 · 生物医学工程
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ACS Applied Materials & Interfaces · 2021 · IF 9.229

Hypoxia-Adapted Sono-chemodynamic Treatment of Orthotopic Pancreatic Carcinoma Using Copper Metal–Organic Frameworks Loaded with an Ultrasound-Induced Free Radical Initiator

Yu Sun,Jing Cao,Xue Wang,Cong Zhang,Jiali Luo,Yiqing Zeng,Chao Zhang,Qunying Li,Ying Zhang,Wen Xu,Tao Zhang,Pintong Huang

The efficacy of sonodynamic therapy (SDT) is largely dependent upon oxygen availability to generate deleterious reactive oxygen species, and as such, hypoxic microenvironments greatly constrain the efficacy of SDT. Development of free radical generators that are not dependent on oxygen and related combination treatment strategies thus have the potential to enhance the antitumor potential of SDT. Combined treatment strategies are expected to improve the efficacy of sonodynamic antitumor therapy. As metal–organic framework (MOF) platforms are highly amenable to integration with other therapeutic approaches, we herein report the development of tumor microenvironment (TME)-responsive nanoparticles constructed by embedding the azo initiator 2,2′-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride (AIPH) into hypoxia-triggered copper metal–organic framework (Cu-MOF) nanovectors to achieve synergistic sono-chemodynamic therapy in an orthotopic murine pancreatic carcinoma model system. When exposed to hypoxic conditions within the TME, this Cu-MOF structure underwent degradation, leading to the release of Cu2+ and AIPH. Cu2+ was then able to deplete local glutathione stores, resulting in the reduction of Cu2+ to Cu+, which then reacts with endogenous H2O2 in a Fenton-like reaction to yield cytotoxic hydroxyl radicals (•OH) for chemodynamic therapy. When exposed to ultrasound irradiation, AIPH further degraded in an oxygen-independent manner to yield nitrogen bubbles and alkyl radicals, the former of which enhanced the ability of these nanoparticles to penetrate deeply into the tumor. The resultant radicals induced substantial DNA damage and apoptotic cell death within target tumors under different levels of oxygen availability. As such, this hypoxic TME-responsive synergistic sono-chemodynamic approach offers an ideal means of achieving oxygen-independent free radical generation and enhanced treatment efficacy.

CAS / MDL: 2997-92-4
研究领域: 肿瘤学 · 纳米技术 · 癌症治疗策略 · 生物医学工程
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Nanoscale · 2022 ·Vol. 14 ·期 27 ·9702-9714 · IF 8.307

Flexible CuS-embedded human serum albumin hollow nanocapsules with peroxidase-like activity for synergistic sonodynamic and photothermal cancer therapy

Haijiao Wang,Jun Tao,Chaoli Xu,Ying Tian,Guangming Lu,Bin Yang,Zhaogang Teng

Nanoparticle flexibility is an important parameter in determining cell uptake and tumor accumulation, thus modulating therapeutic efficiency in cancer treatment. Herein, we successfully prepared CuS-embedded human serum albumin hollow nanocapsules (denoted CuS/HSA) by a hard-core-assisted layer-by-layer coating approach. This approach afforded CuS/HSA hollow nanocapsules with controllable shell thickness, tunable flexibility, uniform size (272.9 nm), a large hollow cavity, peroxidase-like activity, excellent photothermal conversion ability, and a high tetra-(4-aminophenyl) porphyrin (TAPP) loading capacity (27.3 wt%). The peroxidase-like activity of the CuS nanoparticles enabled them to overcome tumor hypoxia and augment the sonodynamic therapeutic (SDT) effects and photothermal conversion ability for photothermal therapy (PTT). In vitro experiments showed that the CuS/HSA-TAPP hollow nanocapsules efficiently induced cancer cell apoptosis under US irradiation and cancer cell ablation under laser irradiation, thus facilitating synergistic SDT and PTT. Importantly, the flexibility of the CuS/HSA hollow nanocapsules resulted in significantly enhanced cellular internalization and a longer mean residence time (131.3 h) than their solid counterparts (21.0 h). In a breast tumor model, the flexible CuS/HSA hollow nanocapsules exhibited high tumor accumulation of up to 27.1%. In vivo experiments demonstrated that the flexible CuS/HSA-TAPP hollow nanocapsules effectively eliminated breast tumors via the synergistic effect of SDT and PTT.

研究领域: 纳米技术 · 癌症治疗 · 材料科学 · 生物医学工程
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