ULTRASOUND IN MEDICINE AND BIOLOGY
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2022
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IF 3.694
Shifang Guo,Zhen Ya,Pengying Wu,Lei Zhang,Mingxi Wan
High-intensity focused ultrasound (HIFU) thrombolysis provides a targeted and non-invasive therapy for thrombosis-related diseases. Rapid thrombolysis and restoration of blood flow are vital to reduce the disability and death rate . The objective of this study was to explore the feasibility of using a high-intensity focused acoustic vortex (HIFAV) to enhance sonothrombolysis. The in vitro clots were treated with HIFU with a peak negative pressure (PNP) of 2.86 MPa (HIFU A) or 3.27 MPa (HIFU B) or HIFAV with a PNP of 2.14 MPa. The results revealed that HIFAV thrombolysis could achieve a significantly higher efficiency than HIFU (HIFAV: 65.4%, HIFU A: 24.1%, HIFU B: 31.6%, p < 0.01), even at a lower intensity. The average size of the debris particles generated in HIFAV thrombolysis was similar to that in HIFU. Additionally, the cavitation activities were found to be more intense in HIFAV thrombolysis. Although the efficiency of HIFAV thrombolysis was higher when the pulse repetition frequency increased from 100 to 500 Hz (41.4% vs. 65.4%, p < 0.05), it decreased when the PRF reached 1000 Hz (29.9%). Lastly, it was found that increasing the duty cycle from 5% to 15% led to a higher efficiency in HIFAV thrombolysis (40.3% vs. 75.2%, p < 0.001). This study illustrated that HIFAV provided enhanced thrombolysis and that its efficiency could be further increased by optimizing the ultrasound parameters.
研究领域:
生物医学工程
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超声治疗
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血栓性疾病
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DOI
高影响因子
Science Advances
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2024
·Vol. 10
·期 5
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IF 11.7
Ben Wang,Qinglong Wang,Kai Fung Chan,Zhipeng Ning,Qianqian Wang,Fengtong Ji,Haojin Yang,Shuai Jiang,Zifeng Zhang,Bonaventure Yiu Ming Ip,Ho Ko,Jacqueline Pui Wah Chung,Ming Qiu,Jianguo Han,Philip Wai Yan Chiu,Joseph Jao Yiu Sung,Shiwei Du,Thomas Wai Hong Leung,Simon Chun Ho Yu,Li Zhang
Micro/nanorobots provide a promising approach for intravascular therapy with high precision. However, blood vessel is a highly complex system, and performing interventional therapy in those submillimeter segments remains challenging. While micro/nanorobots can enter submillimeter segments, they may still comprise nonbiodegradable parts, posing a considerable challenge for post-use removal. Here, we developed a retrievable magnetic colloidal microswarm, composed of tPA-anchored Fe3O4@mSiO2 nanorobots (tPA-nbots), to archive tPA-mediated thrombolysis under balloon catheter-assisted magnetic actuation with x-ray fluoroscopy imaging system (CMAFIS). By deploying tPA-nbot transcatheter to the vicinity of the thrombus, the tPA-nbot microswarms were magnetically actuated to the blood clot at the submillimeter vessels with high precision. After thrombolysis, the tPA-nbots can be retrieved via the CMAFIS, as demonstrated in ex vivo organ of human placenta and in vivo carotid artery of rabbit. The proposed colloidal microswarm provides a promising robotic tool with high spatial precision for enhanced thrombolysis with low side effects.
研究领域:
医学工程
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生物材料
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介入治疗
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2025
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IF 19
Huan Zheng,Pan Ran,Wenxiong Cao,Guiyuan Zhang,Yupeng Su,Kang Zhang,Xiaohong Li
Triboelectric nanogenerators convert the mechanical energy of human body motions into sustained electric powers, but the triboelectric effect is not yet integrated with pathological microenvironments. Herein, endogenous shear stress-responsive platforms are designed for tribocatalytic thrombolysis through sequential deposition of SiO 2 and Au layer onto tetragonal barium titanate (tBT) nanoparticles (NPs), followed by SiO 2 layer etching and surface grafting of arginine-glycine-aspartic acid (RGD) to obtain yolk–shell-structured tBT@Au-RGD NPs. High-frequency frictions and collisions between tBT yolks and Au shells continuously stimulate electron–hole pairs and reactive oxygen species (ROS) generations, and the dynamic Schottky junctions provide electron channels from tBT to Au to inhibit electron–hole recombinations. The piezopotential of tBT further promotes electron–hole separations and acts synergistically with tribovoltaic ROS generation for degrading fibrin networks of thrombi. In a loop-closed flow system demonstrates shear stress-adaptable ROS generations under embolization degrees from 20% to 80%. In a carotid thrombosis model RGD grafts increase NP accumulations four folds at the thrombus site after 24 h of intravenous administration, and the stenosis degree is reduced to 3.99% with complete blood vessel recanalization and negligible bleeding risk and systemic toxicity. This study is the first attempt to demonstrate endogenous stimuli-induced tribovoltaic and piezoelectric effects for tribocatalytic disease treatment.
研究领域:
生物医学工程
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纳米医学
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催化医学
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产品关联
DOI
高影响因子
PHARMACOLOGICAL RESEARCH
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2025
·
IF 10.5
Ning Yu,Shule Zhang,Rui Fang,Yingxin Zhang,Xi Xu,Lijuan Cao,Jianfa Zhang
Clinically approved thrombolytic agents carry significant bleeding risks due to systemic plasminogen activation. Heparin analogs prevent thrombus formation but lack direct thrombolytic activity. Here, we report a previously unrecognized thrombolytic mechanism of octaparin, a synthetic heparin analog. Studies demonstrated that octaparin exhibits potent anticoagulant and thrombolytic activity both in vitro and in vivo , with a lower bleeding risk compared to conventional heparin-based agents. Octaparin directly binds fibrin monomers, altering their secondary conformation to inhibit polymerization and destabilize preformed thrombi, while preserving tissue factor-driven coagulation. In murine models of pulmonary embolism and inferior vena cava thrombosis, octaparin both prevented and dose-dependently dissolved established clots without compromising hemostatic integrity, sharply contrasting with conventional thrombolytics that induce hemorrhage. Further analyses using molecular docking, microscale thermophoresis, and spectroscopy confirmed that octaparin induces changes in fibrin monomer folding that compromise fibrin network stability. In human systems, octaparin selectively prolonged intrinsic coagulation time, reduced clot retraction, did not induce platelet activation, and its effects were reversible with protamine sulfate. This study establishes targeted fibrin destabilization as a viable therapeutic strategy, revealing a previously unrecognized thrombolytic mechanism achievable through heparin-based molecular design.
研究领域:
药理学
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血液学
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分子医学
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血管生物学
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抗凝治疗
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转化医学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
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2025
·
IF 4.8
Yu-Ming Huang,Cheng-Rang Liu,Yi-Qi Xu,Chao Cao,Zhen-Gan Huang,Hong-Wen Fei,Yue-Shan Huang
Objective: This study aimed to develop a poly (lactic-co-glycolic acid) (PLGA)-based magnetic loaded iron oxide (Fe3O4) and single-chain urokinase-type plasminogen activator (proUK) for enhancing thrombolysis under a controlled rotating magnetic field, specifically targeting acute lower limb venous thrombosis.Background: Acute thrombotic disorders are significant health threats, however, the exploration of magnetic actuation as a treatment for acute thrombosis has been limited.Methods: Magnetic microbubbles were prepared using a double emulsion method, loaded with Fe3O4 nanoparticles and proUK. The microbubble characteristics were analyzed through chemical, physical, and biological related technologies.Results: Fe3O4 nanoparticle loading was confirmed by X-ray diffraction, and the encapsulation efficiency of the magnetic microbubbles was determined using an ELISA kit and colorimetric assay, reaching a maximum of 56.65% at a proUK concentration of 7.5 mg/mL. Thrombolysis efficiency was significantly enhanced under a rotating magnetic field of 1.5 mT and 6 Hz frequency, achieving up to 25% lysis rate in vitro, markedly higher than control conditions. Furthermore, in vivo experiments using a rabbit model of hindlimb venous thrombosis validated the efficacy of this approach, with Color Doppler Flow Imaging showing restored blood flow and elevated D-dimer levels indicating effective thrombus dissolution.Conclusion: This novel magnetic drug delivery system, combined with a rotating magnetic field, demonstrates excellent thrombolysis efficiency and presents a promising and safe therapeutic strategy for acute venous thrombosis.
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产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
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2018
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IF 4.56
Yang Pan,Xiahui Wang,Zongning Yin
To achieve targeted thrombolysis, a targeted delivery system of lumbrokinase (LK) was constructed using RGDfk-conjugated hybrid micelles. Based on the specific affinity of RGDfk to glycoprotein complex of GPⅡb/Ⅲa expressed on the surface of membrane of activated platelet, LK loaded targeted micelles (LKTM) can be delivered to thrombus. The hybrid micelles were composed of polycaprolactone-block-poly (2-(dimethylamino) ethyl methacrylate) (PCL-PDMAEMA), methoxy polyethylene glycol-block- polycaprolactone (mPEG-PCL) and RGDfk conjugated polycaprolactone-block- polyethylene glycol (PCL-PEG-RGDfk). PCL-PDMAEMA was synthesized via ring open polymerization (ROP) and atom transfer radical polymerization (ATRP). PCL-PEG-RGDfk was synthesized via ROP and carbodiimide chemistry. The prepared LKTM was characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). Colloidal stability assay showed the prepared LKTM was stable. Biocompatibility assay was performed to determine the safe concentration range of polymer. The assay of fluorescent distribution in vivo demonstrated that LKTM can be efficiently delivered to thrombi in vivo . Thrombolysis in vivo indicated the thrombolytic potency of LKTM was optimal in all groups. Notably, the laboratory mice treated with LKTM exhibited a significantly shorter tail bleeding time compared to those treated with LK or LK-loaded micelles without RGDfk, which suggested that the targeted delivery of LK using RGDfk-conjugated hybrid micelles effectively reduced the bleeding risk.
研究领域:
药剂学
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生物医学工程
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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