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ACS Applied Bio Materials · 2020 · IF 0

Three Birds with One Stone: Injectable CaC2 Nanobombs with Triple Effects for Minimally Invasive Tumor Chemical Ablation

Hongguang Liao,Yuting Zeng,Shenglong Liao,Yanji Chu,You Zhou,Yapei Wang

Percutaneous chemical ablation (PCA) is the oldest and most established technique for treating small solid tumors in organs. It has been widely used in clinics even on an outpatient basis. However, compared with the emerging microwave or magnetic hyperthermal ablation, PCA is faced with relatively poor necrosis results and needs to repeat multiple sessions. Inspired by the three effects in the bomb’s explosive process, we herein expect to combine calcium carbide (CaC2) nanoparticles into the PCA technique to generate local explosion within tumor tissues, leading to three killing effects against tumors to further improve the ablation efficacy of PCA. Through an efficient wet milling procedure with poly(ethylene glycol), three kinds of nanobombs including CaC2, calcium oxide (CaO), and calcium hydroxide (Ca(OH)2) were fabricated, and they all exhibited desirable suspension stability. Among these nanobombs, in particular CaC2 nanobombs showed a synergistic effect that the generation of ethyne gas bubbles could facilitate the most rapid diffusion of hyperthermia. Also, CaC2 nanobombs offered the powerful ability to cause the sudden rise of local high temperature and pH value. According to the in vivo mice tumor excision trial, the tumors of 75% of cases that received CaC2 treatment were destroyed and eradicated, exhibiting the excellent ablation ability of CaC2 nanobombs against small solid tumors planted in mice.

研究领域: 纳米技术 · 肿瘤学 · 生物医学工程
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Bioactive Materials · 2023 · IF 18.9

Development and preclinical evaluation of multifunctional hydrogel for precise thermal protection during thermal ablation

Bowen Zheng,Peng Zhang,Qijun Lv,Tao Wu,Yadong Liu,Junjie Tang,Yanping Ma,Lili Cheng,Langtao Xu,Yizhen Wang,Yifan Xue,Jie Liu,Jie Ren

Image-guided thermal ablation (TA), which is less invasive, has been widely applied for treating various kinds of tumors. However, TA still poses the potential risk of thermal damage to sensitive tissue nearby. Therefore, an adjunctive thermoprotective hydrodissection technique with constant injection of 5% glucose (5% Glu) has currently been adopted for clinical application, but this may be hazardous to humans. In this study, a multifunctional hyaluronic acid-based hydrogel (HA-Dc) was developed for hydrodissection. Compared with 5% Glu (the most clinically used solution) and the previously reported F127 hydrogel, the HA-Dc hydrogel was studied in vitro in a porcine liver model and in vivo in a rabbit model and showed good injectability and better tissue retention, stability, and thermoprotective properties throughout the TA procedure. Furthermore, in the preclinical evaluation in a Macaca fascicularis (M. fascicularis) model, HA-Dc showed excellent performance in terms of stricter neuroprotection compared with 5% Glu. In addition, the HA-Dc hydrogel with good biocompatibility and controllable degradation behavior in vivo could be a promising platform for thermal protection during clinical TA procedures.

研究领域: 医学工程 · 生物材料学
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JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY · 2022 ·Vol. 38 ·期 1 ·156-165 · IF 4.351

Accurate determination of rare earth elements in small volumes of porewater from marine sediments by laser ablation solution sampling ICP-MS

Xiuhong Liao,Wen Zhang,Tao Yang,Zhaochu Hu,Tao Luo,Xianli Zeng,Lian Zhou

Rare earth elements (REEs) in porewater can be useful proxies in the studies of marine geochemistry. The main challenges for the determination of REEs in porewater samples from marine sediments lie in three aspects—low concentration, high salinity, and limited sample sizes (usually only a few millilitres). In this study, a method based on laser ablation (LA) solution sampling ICP-MS for REEs analysis of small volumes (2–4 mL) of porewater is established. With the help of matrix removal and REEs preconcentration from natural liquids by a miniaturized Fe(OH)3 co-precipitation method, a high enrichment factor (10–20 fold) was achieved with only 2 mL of the original liquid, which was preconcentrated to be as small as 100–200 μL. Ultratrace (sub-pg mL−1) analysis was realized through the use of high laser ablation pulse frequency (up to 250 Hz) and based on the high transport efficiency of aerosol particles by the LA system. Due to the almost “dry” ICP condition generated by LA and nitrogen addition (5 mL min−1) to the plasma, the CeO+/Ce+ ratio was reduced to approximately 0.05%, and the total yields of BaO+ and BaOH+ ions were reduced to 0.003%, which means that the potential biases induced by oxide and hydroxide interferences could be negligible. Method validation was achieved through the analysis of the seawater reference material NASS-7 and a spike recovery test with quantitative recoveries of 94–101% for REEs. The application results of porewater samples characterized by no or slight Ce anomalies together with significantly positive Eu anomalies may be indicative of highly reducing and neutral to basic pH conditions. Reagents consumed by the LA-ICP-MS method were significantly reduced, making it a more environment-friendly method. Moreover, the simplicity in sample preparation and lack of need for special reagents or devices give the proposed method great potential for wide applications in the determination of REEs in natural water samples.

CAS / MDL: 1336-21-6
研究领域: 海洋化学 · 分析化学
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INTERNATIONAL JOURNAL OF HYPERTHERMIA · 2022 · IF 3.753

A novel tissue-mimicking phantom for US/CT/MR-guided tumor puncture and thermal ablation

Xinyu Zhong,Ping Zhou,Yongfeng Zhao,Wengang Liu,Xinghao Zhang

Aim This study aimed to develop a novel tumor-bearing tissue phantom model that can be used for US/CT/MR-guided tumor puncture and thermal ablation.Methods The phantom model comprised two parts: a normal tissue-mimicking phantom and a tumor-mimicking phantom. A normal tissue phantom was prepared based on a polyacrylamide gel mixed with thermochromic ink. Moreover, a spherical phantom containing contrast agents was constructed and embedded in the tissue phantom to mimic a tumor lesion. US/CT/MR imaging features and thermochromic property of the phantom model were characterized. Finally, the utility of the phantom model for imaging-guided microwave ablation training was examined.Results The tumor phantom containing contrast agents showed hyper-echogenicity, higher CT numbers, and lower T2 signal intensity compared with the normal tissue phantom in US/CT/MR images. Consequently, we could locate the position of the tumor in US/CT/MR imaging and perform an imaging-guided tumor puncture. When the temperature reached the threshold of 60 °C, the phantom exhibited a permanent color change from cream white to magenta. Based on this obvious color change, our phantom model could clearly map the thermal ablation region after thermotherapy.Conclusions We developed a novel US/CT/MR-imageable tumor-bearing tissue model that can be used for imaging-guided tumor puncture and thermal ablation. Furthermore, it allows visual assessment of the ablation region by analyzing the obvious color change. Overall, this phantom model could be a good training tool in the field of thermal ablation.

研究领域: 医学影像学 · 肿瘤学
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JOURNAL OF ULTRASOUND IN MEDICINE · 2024 · IF 2.1

Interaction Between Microbubbles and Microwave Ablation

Xinyu Zhong,Xinghao Zhang,Yuting Cao,Ping Zhou

Objectives This study aimed to explore the interactions between microbubbles and microwave ablation (MWA). Methods The study employed custom-made phantoms (in vitro) and white New Zealand rabbits (in vivo). MWA was performed with or without microbubbles in the phantoms (2 × 10 5 particles mL −1 ) and rabbit livers (intravenous injection of 0.05 mL/kg SonoVue). During the MWA, K-type thermocouple probes were used to monitor the MWA-induced temperature increase. Contrast-enhanced ultrasound imaging (CEUS) was used to monitor and analyze the microbubbles signal intensity. After MWA, the ablation-zone volumes were evaluated and compared between the groups with and without microbubbles. Results In both the phantom models and rabbits, microbubbles showed no significant influence on MWA, including the ablation range and MWA-induced temperature increase. In phantoms and rabbit livers filled with microbubbles, MWA caused the formation of a gradually expanding microbubble-defect region over the ablation time. An increase in the temperature caused microbubble destruction. Conclusions Microbubbles had no significant influence on MWA. However, MWA induced the destruction of microbubbles in a temperature-dependent manner. Thus, the poor thermotolerance of microbubbles is a non-negligible barrier when using CEUS to monitor the ablation range during MWA in real-time.

研究领域: 医学影像学 · 肿瘤学
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ADVANCED FUNCTIONAL MATERIALS · 2024 · IF 18.5

Colloidal Hydrogel for Sensitizing Microwave Ablation-Induced in Situ Tumor Vaccination and Modulating Innate and Adaptive Immunotherapy

Tian Tian,Jingguo Wang,Weitao Wang,Haitao Wu,Qianhui Li,Fei Wang,Hua Wang,Zhengbao Zha

Drawing inspiration from recent advances in microwave ablation (MWA) induced in situ tumor vaccination, a colloidal hydrogel comprising amphoteric gelatin nanoparticles and poly (acrylic acid) (PAA)-calcium carbonate nanorods (PAA-CaCO 3 NRs) is developed to deliver the microwave-sensitive agent sodium fluoride (NaF) which can also act as a glycolysis inhibitor in conjunction with the blockade of the T-cell Ig and ITIM domain (TIGIT), a coinhibitory receptor expressed by both natural killer (NK) cells and T cells. The combination of NaF with microwave (MW) thermal-dynamic sensitization effectively reversed the acidic and immunosuppressive tumor microenvironment (TME). Moreover, the incorporation of anti-TIGIT monoclonal antibody (aTIGIT) molecules amplified both the innate and adaptive immune responses by counteracting the exhaustion of NK and effective CD8 + T cells. This augmentation resulted in enhanced tumor elimination and suppression of tumor metastasis and recurrence. Thus, this study underscores the potential of colloidal hydrogel-sensitized MWA therapy, in conjunction with aTIGIT treatments, as a promising clinical strategy for in situ cancer vaccination.

CAS / MDL: 90-80-2 9003-01-4
研究领域: 肿瘤学 · 生物医学工程 · 免疫学
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Cancer Nanotechnology · 2025 ·Vol. 16 ·期 1 ·1-19 · IF 4.8

Bacteria-based drug-loaded mesoporous silica nanoparticles for synergistic FUAS of breast cancer

Zhang Mingyang,Zhou Yijun,Yang Haiyan,Zheng Guangrong,Ren Li,Zhang Zhong,Lin Li,He Youqian,Wang Qi,Zou Jianzhong

Focused ultrasound ablation surgery (FUAS), a minimally invasive therapeutic strategy, has demonstrated potential in breast cancer treatment but is limited by incomplete tumor irradiation and the damage to normal tissues. Here, we present a novel platform utilizing mesoporous silica nanoparticles (MSNs), functionalized with polyethylene glycol (PEG) and polyethyleneimine (PEI), encapsulating astragaloside IV (AS) and gated with 1-tetradecanol (TD). These NPs (PP@M-TD/AS) attach to Bifidobacterium bifidum ( BF ) via electrostatic adsorption. Leveraging BF 's tumor-targeting ability in hypoxic microenvironments, the NPs enable specific accumulation in tumor site, facilitating targeted and efficient drug delivery. FUAS-induced thermal effects trigger the phase transition of TD, facilitating on-demand AS release at the tumor site. This approach enhances FUAS-mediated tumor ablation by improving acoustic impedance and ensuring precise drug delivery, leading to significant tumor suppression. Moreover, the system exhibited extended retention at the tumor site and excellent biocompatibility with minimal systemic toxicity. This platform effectively addresses the limitations of FUAS, offering a highly efficient and targeted approach for advancing breast cancer therapy. Graphical

研究领域: 医学 · 生物材料学 · 肿瘤学
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Scientific Reports · 2013 ·Vol. 3 ·期 1 ·1-8 · IF 2.927

Polypyrrole Hollow Microspheres as Echogenic Photothermal Agent for Ultrasound Imaging Guided Tumor Ablation

Zha Zhengbao,Wang Jinrui,Qu Enze,Zhang Shuhai,Jin Yushen,Wang Shumin,Dai Zhifei

Ultrasound (US) imaging provides a valuable opportunity to administer photothermal therapy (PTT) of cancer with real-time guidance to ensure proper targeting, but only a few theranostic agents were developed by physically grafting near infrared (NIR)-absorbing inorganic nanomaterials to ready-made ultrasound contrast agents (UCAs) for US imaging guided PTT. In this paper, NIR absorbing hollow microspheres were generated from polypyrrole merely using a facile one-step microemulsion method. It was found that the obtained polypyrrole hollow microspheres (PPyHMs) can act as an efficient theranostic agent not only to enhance US imaging greatly, but also exhibit excellent photohyperthermic effects. The contrast consistently sustained the echo signals for no less than 5 min and the NIR laser light ablated the tumor completely within two weeks in the presence of PPyHMs. More importantly, no use of additional NIR absorber substantially minimizes an onetime dose of the theranostic agent.

研究领域: 生物医学工程 · 癌症治疗
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CHEMICAL ENGINEERING JOURNAL · 2022 · IF 16.744

Radiofrequency-thermal effect of cisplatin-crosslinked nanogels for triple therapies of ablation-chemo-embolization

Ling Li,Hongsen Zhang,Hao Zhao,Dingwen Shi,Chuansheng Zheng,Yanbing Zhao,Xiangliang Yang

Improving the synergistic effect of radiofrequency ablation (RFA) and trans -artery chemo-embolization (TACE) remains the main challenge in interventional cancer therapy. The present study reports cisplatin-crosslinking poly( N -isoprylacrylamide- b -methyl acrylic acid) nanogels (Pt-PNA) based on the RF-thermal effect of cisplatin as the RF-responsive embolic nano-platform that acts via coordination bonding between Pt(II) ions and carboxyl, thereby triggering cell apoptosis, necrosis, and metastasis inhibition. Moreover, Pt-PNA might diffuse rapidly into tumor peripheral arteries and block the tumor blood supply facilitated by temperature-sensitive sol–gel transition, thereby achieving efficient TACE cancer therapy. The antitumor efficacy exhibited in vivo by Pt-PNA indicated that the radiofrequency-responsive Pt-PNA greatly improved the hypoxic tumor microenvironment after the TAE procedure, thereby inducing a favorable immune response and enhancing the synergistic antitumor effect of RFA and TACE.

CAS / MDL: 76-05-1 7761-88-8
研究领域: 医学 · 生物材料学 · 肿瘤学
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Nano Today · 2021 · IF 20.722

Targeted delivery of Bi2Se3 Nanoflowers to orthotopic liver tumor via transarterial infusion for enhanced microwave ablation sensibilization

Long Gao,Haili Yan,Shuang Zhu,Xiaochun Wang,Yan Tan,Jiangfeng Du,Duiping Feng,Hui Zhang,Zhanjun Gu

Microwave ablation (MWA) is acknowledged as one of the optimal therapeutic strategies for unresectable hepatocellular carcinoma (HCC). Unfortunately, inadequate MWA at high-risk sites is very common in clinic owing to the scruple of probable damage to adjacent vital organs, which eventually leads to recurrence of residual tumors. Herein, we synthesize novel Bi 2 Se 3 nanoflowers (NFs) which possess the peculiarity of microwave sensibilization and explore their sensitization capability both in vitro and in vivo . The as-prepared NFs exhibits remarkable heating capacity under microwave irradiation compared to deionized water , mainly due to the multilayered petal structures that could strongly increase the reflectivity of microwave and stimulate the motion of water molecules. More importantly, we recruit clinically available transarterial infusion (TAI) method for precisely targeted delivery of Bi 2 Se 3 NFs to tumor site and perform sequential MWA on orthotopic liver tumor. In addition, the high Z element containing Bi 2 Se 3 NFs could realize efficient computed tomography to monitor the therapeutic process. What’s more, no obvious cell and organic toxicity are observed during the experimental period, which further verifies the good biocompatibility of Bi 2 Se 3 NFs. In this work, we utilize minimally invasive TAI for targeted delivery of microwave sensitive nanoflowers to improve MWA efficacy at tumor site and reduce side effect in normal tissues, which provides a neoteric theoretical and experimental strategy for clinical interventional therapy of HCC.

研究领域: 医学影像学 · 肿瘤学 · 生物材料学
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Frontiers in Oncology · 2021 · IF 6.244

Evaluation of Microwave Ablation in 4T1 Breast Tumor by a Novel VEFGR2 Targeted Ultrasound Contrast Agents

Li Xiaoyu,Xia Shujun,Ji Ri,Zhan Weiwei,Zhou Wei

Objectives: A novel ultrasound contrast agent (UCA) VEGFR2-targeting iron-doped silica (SiO2) hollow nanoparticles (VEGFR2-PEG-HSNs-Fe NPs) was prepared and applied in microwave ablation for breast cancer to investigate its value in the evaluation of effectiveness after tumor ablation.Methods: VEGFR2-PEG-HSNs-Fe NPs were prepared by using nano-SiO2, which was regarded as a substrate and etched by ferrous acetate, and then modified with anti-VEGFR2 antibody. Laser confocal microscope and flow cytometry were used to observe its main physicochemical properties, and biological safety was also investigated. After the xenograft tumor was treated with microwave ablation, the extent of perfusion defect was evaluated by ultrasound by injecting VEGFR2-PEG-HSNs-Fe NPs.Results: The average particle size of VEGFR2-PEG-HSNs-Fe was 276.64 ± 30.31 nm, and the surface potential was −13.46 ± 2.83 mV. In vitro, the intensity of ultrasound signal increased with UCA concentration. Good biosafety was performed in in vivo and in vitro experiments. The enhanced ultrasound signal was detected in tumors after injection of VEGFR2-PEG-HSNs-Fe NPs, covering the whole tumor. The lesions, which were incompletely ablated, presented as contrast agent perfusion at the periphery of the tumor, and contrast enhanced ultrasound (CEUS) was performed again after complementary ablation. It was confirmed that all the lesions were completely ablated.Conclusion: Nano-targeted UCAs VEGFR2-PEG-HSNs-Fe NPs had good biosafety and ability of specific imaging, which might be used as a contrast agent in CEUS to evaluate the efficacy of tumor ablation.

研究领域: 医学影像学 · 肿瘤学 · 生物材料学
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Materials Today Bio · 2024 · IF 8.7

Intelligent nanocatalyst mediated lysosomal ablation pathway to coordinate the amplification of tumor treatment

Mingliang Pei,Xin Guan,De Zhao,Fan Yang,Yun Dong,Manxiu Huai,Wensong Ge,Xiaodong Hou,Wenfeng Chu,Kai Wang,Jie Chen,Huixiong Xu

The production of reactive oxygen species (ROS) is susceptible to external excitation or insufficient supply of related participants ( e.g. , hydrogen peroxide (H 2 O 2 ) and sensitizer), liming ROS-driven tumor treatment. Additionally, the lysosomal retention effect severely hinders the utilization of ROS-based nanosystems and severely restricted the therapeutic effect of tumors. Therefore, first reported herein an intelligent nanocatalyst, TCPP-Cu@MnO x ((Mn II ) 1 (Mn III ) 2.1 (Mn IV ) 2.6 O 9.35 ), and proposed a programmed ROS amplification strategy to treat tumors. Initially, the acidity-unlocked nanocatalyst was voluntarily triggered to generate abundant singlet oxygen ( 1 O 2 ) to mediate acid lysosomal ablation to assist nanocatalyst escape and partially induce lysosomal death, a stage known as lysosome-driven therapy. More unexpectedly, the high-yielding production of 1 O 2 in acid condition (pH 5.0) was showed compared to neutral media (pH 7.4), with a difference of about 204 times between the two. Subsequently, the escaping nanocatalyst further activated H 2 O 2 -mediated 1 O 2 and hydroxyl radical (•OH) generation and glutathione (GSH) consumption for further accentuation tumor therapy efficiency, which is based on the Fenton-like reaction and Russell reaction mechanisms. Therefore, in this system, a program-activatable TCPP-Cu@MnO x nanocatalyst, was proposed to efficiently destruct organelle-lysosome via 1 O 2 inducing, and stimulated H 2 O 2 conversion into highly toxic 1 O 2 and •OH in cytoplasm, constituting an attractive method to overcome limitations of current ROS treatment.

研究领域: 医学 · 生物化学 · 纳米医学
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