COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Ning Yang,Weikun Li,Zhicheng Qian,Xin Tan,Zonghao Liu,Feiling Feng,Ling Liu,Liqin Ge
Pulmonary embolism remains the third leading cause of human mortality after malignant tumors and myocardial infarction. Commonly available thrombolytic therapeutic agents suffer from the limitations of very short half-life, inadequate targeting, limited clot penetration, and a propensity for severe bleeding. Inspired by the trident, we developed the armor-piercing microcapsule (MC), fucoidan-urokinase-S-nitrosoglutathione-polydopamine@MC (FUGP@MC), which exhibited a triple combination of photothermal, mechanical and pharmacological thrombolysis for the therapeutic treatment of acute pulmonary embolism (APE). Briefly, the outermost fucoidan layer was utilized for targeting to the APE area. Programmed APE treatment was triggered by near-infrared (NIR) light irradiation. Photothermal thrombolytic therapy was carried out by photothermal conversion of polydopamine. The photothermal conversion broke the S-nitroso bond in S-nitrosoglutathione (GSNO) and produced large amounts of nitric oxide (NO) for mechanical thrombolysis, which subsequently disrupted the interfacial structure of microcapsule to stimulate the release of the urokinase (UK), leading to a triple synergistic thrombolytic effect. The results demonstrated that the embolization residual rate of FUGP@MC (contained ≈ 1452.5 IU/kg UK) group was significantly lower than that of UK (10,000 IU/kg) group (6.35 % VS 16.78 %). Remarkably, FUGP@MC demonstrated a reliable in vivo biosafety proficiency. In summary, trident-inspired armor-piercing microcapsule FUGP@MC reveals a potential avenue for advancing pulmonary embolism therapeutics and promises to be a safer alternative candidate to current drug approaches.
研究领域:
药学
·
生物医学工程
·
治疗技术
·
材料科学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Wenxiong Cao,Yuan Liu,Pan Ran,Jie He,Shuang Xie,Jie Weng,Xiaohong Li
Antithrombosis therapy is confronted with short half-lives of thrombolytic agents, limited therapeutic effects, and bleeding complications. Drug delivery systems of thrombolytic agents face challenges in effective penetration into thrombi, which are characterized by well-organized fibrin filled with abundant activated platelets. Herein, Janus rod (JR)-shaped micromotors are constructed by side-by-side electrospinning and cryosection, possessing advantages in controlling the Janus structure and aspect ratio of microrods. Silicon phthalocyanine (Pc) and CaO2 nanoparticles (NPs) are loaded into the separate sides of JRs, and Arg-Gly-Asp (RGD) peptides are grafted on the surface to obtain Pc/Ca@r-JRs for the sonodynamic therapy (SDT) of thrombosis without using any thrombolytic agents. Decomposition of CaO2 NPs ejects O2 bubbles from one side of JRs, and ultrasonication of O2 bubbles produces the cavitation effect, both generating mechanical force to drive the thrombus penetration. The integration of ultrasonication-propelled motion and RGD mediation effectively increases the targeting capabilities of r-JRs to activated platelets. In addition to mechanical thrombolysis, ultrasonication of the released Pc produces 1O2 to destruct fibrin networks of clots. In vitro thrombolysis of whole blood clots shows that ultrasonication of Pc/Ca@r-JRs has a significantly higher thrombolysis rate (73.6%) than those without propelled motion or RGD-mediated clot targeting. In a lower limb thrombosis model, intravenous administration of Pc/Ca@r-JRs indicates 3.4-fold higher accumulations at the clot site than those of JRs, and ultrasonication-propelled motion further increases thrombus retention 2.1 times. Treatment with Pc/Ca@r-JRs and ultrasonication fully removes thrombi and significantly prolongs tail bleeding time. Thus, this study has achieved precise and prompt thrombolysis through selective targeting to clots, efficient penetration into dense networks of thrombi, and SDT-executed thrombolysis.
研究领域:
生物医学工程
·
治疗学
·
纳米技术
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Yanzhen Song,Juanfeng Ou,Jiajun Miao,Xiaoting Zhang,Jiamiao Jiang,Hao Tian,Fei Peng,Yingfeng Tu
Current thrombolytic drugs exhibit suboptimal therapeutic outcomes and potential bleeding risks due to their limited circulation time, inadequate thrombus penetration, and off-target biodistribution. Herein, a photosensitizer-loaded, red cell membrane-encapsuled multiple magnetic nanoparticles aggregate is successfully developed for integrated mechanical/photothermal/photodynamic thrombolysis. Red cell membrane coating endows magnetic particles with prolonged blood circulation and superior biocompatibility. Under a preset rotating magnetic field (RMF), the aggregate with asymmetric magnetic distribution initiates rolling motion toward the blood clot interface, and because of magnetic dipole-dipole interactions, the aggregate tends to self-assemble into longer, flexible chain-like microrobotic swarm with powerful mechanical stir forces, thereby facilitating thrombus penetration and mechanical thrombolysis. Moreover, precise magnetic control enables targeted photosensitizer accumulation, allowing effective conversion of near-infrared (NIR) light into heat and reactive oxygen species (ROS) for thrombus phototherapy. In thrombolysis assays, the weight of thrombi is massively reduced by ≈90%. The work presents a safer and more promising combination of magnetic microrobotic technology and phototherapy for multi-modality thrombolysis.
研究领域:
生物医学工程
·
治疗诊断学
·
纳米技术
·
生物物理学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2022
·Vol. 18
·期 34
·2202848
·
IF 15.153
Xiuzhen Tang,Laliphat Manamanchaiyaporn,Qi Zhou,Chenyang Huang,Lihuang Li,Ziqiao Li,Longchen Wang,Jienan Wang,Lei Ren,Tiantian Xu,Xiaohui Yan,Yuanyi Zheng
Magnetic micro-/nanoparticles are extensively explored over the past decade as active diagnostic/therapeutic agents for minimally invasive medicine. However, sufficient function integration on these miniaturized bodies toward practical applications remains challenging. This work proposes a synergistic strategy via integrating particle functionalization and bioinspired swarming, demonstrated by recombinant tissue plasminogen activator modified magnetite nanoparticles (rtPA-Fe 3 O 4 NPs) for fast thrombolysis in vivo with low drug dosage. The synthesized rtPA-Fe 3 O 4 NPs exhibit superior magnetic performance, high biocompatibility, and thrombolytic enzyme activity. Benefiting from a customized magnetic operation system designed for animal experiments and preclinical development, these agglomeration-free NPs can assemble into micro-/milli-scale swarms capable of robust maneuver and reconfigurable transformation for on-demand tasks in complex biofluids. Specifically, the spinning mode of the swarm exerts focused fluid shear stresses while rubbing on the thrombus surface, constituting a mechanical force for clot breakdown. The synergy of the NPs’ inherent enzymatic effect and swarming-triggered fluid forces enables amplified efficacy of thrombolysis in an in vivo occlusion model of rabbit carotid artery, using lower drug concentration than clinical dosage. Furthermore, swarming-enhanced ultrasound signals aid in imaging-guided treatment. Therefore, the pharmacomechanical NP swarms herein represent an injectable thrombolytic tool joining advantages of intravenous drug therapy and robotic intervention.
研究领域:
纳米技术
·
药理学
·
生物医学工程
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ULTRASOUND IN MEDICINE AND BIOLOGY
·
2022
·
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
·
超声治疗
·
血栓性疾病
✓ 已验证
DOI
高影响因子
Nanoscale
·
2025
·
IF 5.1
Yaxue Liu,Yu Li,Junlong Chen,Pei Xie,Zongning Yin
The clinical application of conventional thrombolytic drugs is limited due to the difficulty in precisely targeting the thrombus site and side effects such as severe bleeding. In order to specifically image thrombus for diagnosis and thrombolytic therapy, a CREKA-targeted and pH-responsive drug release nano-delivery system, called LK/PDB/IR820-CREKA NPs, was constructed. In vitro experiments showed that NPs had good pH responsiveness and biocompatibility. The in vitro thrombolytic rate was as high as 46% and had a strong thrombus-binding ability. In the FeCl3-induced carotid artery thrombosis model in mice, PDB/IR820-CREKA NPs could specifically target thrombus, which enabled accurate diagnosis of thrombus sites. Targeted nanoparticle-encapsulated Lumbrokinase at a dose of 900 U/10g significantly reduced the total protein content at the thrombus site, while reducing the risk of non-specific bleeding. Based on the thrombus-specific imaging and therapeutic activity, this nano-delivery system has the potential to be used for the treatment of thrombotic vascular diseases.
研究领域:
医学
·
药学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Haoyuan Li,Zhipeng Yang,Qisheng Tang,Zhifeng Shi,Ying Mao
Stroke models are vital tools in neuropharmacology and rehabilitation research. However, a classic and widely used model—the suture occlusion model—is not suitable for all research approaches, especially regarding thrombolysis. For embolic stroke models in thrombolytic research, the surgical procedures of thrombin injection in the middle cerebral artery or clot injection in the carotid artery involved are too sophisticated. Here, we report a new stroke model in mice that uses magnetic nanoparticle (MNP) cross-linked with thrombin to embolize. Briefly, after the magnet was positioned in the common carotid artery, MNP@Thrombin was injected from the tail vein. Within several minutes postinjection, the MNP@Thrombin accumulated in the carotid artery and induced thrombus formation. These complex clots were flushed into and subsequently blocked the cerebral artery. Collectively, these results suggested that this new method was a quick and easy stroke model that blocked hemisphere blood flow and damaged neural function. Importantly, this model had an excellent response to thrombolytic drugs. After urokinase injection, cerebral blood flow was restored and symptom scores were enhanced by nearly one. This method, including a quick synthesis of MNP and thrombin, provided an easy and minimally invasive process for a new stroke model that is usable in both pharmacological and rehabilitative research.
研究领域:
神经药理学
·
康复研究
·
中风模型
·
溶栓
✓ 已验证
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2022
·
IF 14.903
Songli Wang,Ruifeng Wang,Nana Meng,Linwei Lu,Jun Wang,Jianfen Zhou,Jiasheng Lu,Qianzhu Xu,Cao Xie,Changyou Zhan,Yao Li,Yang Yu,Weiyue Lu,Min Liu
Thrombolytic agents have thus far yielded limited therapeutic benefits in the treatment of thrombotic disease due to their short half-life, low targeting ability, and association with serious adverse reactions, such as bleeding complications. Inspired by the natural roles of platelets during thrombus formation, we fabricated a platelet-based delivery system (NO@uPA/PLTs) comprising urokinase (uPA) and arginine (Arg) for targeted thrombolysis and inhibition of re-embolism. The anchoring of uPA to the platelet surface by lipid insertion increased the thrombotic targeting and in vivo circulation duration of uPA without disturbing platelet functions. Nitric oxide (NO) generated by the loaded Arg inhibited platelet aggregation and activation at the damaged blood vessel, thereby inhibiting re-embolism. NO@uPA/PLTs effectively accumulated at the thrombi in pulmonary embolism and carotid artery thrombosis model mice and exerted superior thrombolytic efficacy. In addition, the platelet delivery system showed excellent thrombus recurrence prevention ability in a mouse model of secondary carotid artery injury. The coagulation indicators in vivo showed that the platelet-based uPA and NO co-delivery system possessed a low hemorrhagic risk, providing a promising tool for rapid thrombolysis and efficient inhibition of posttreatment re-embolism.
研究领域:
药学
·
生物医学工程
·
血液学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2017
·
IF 3.887
Shao-Fei Zhang,Chunmei Gao,Shaoyu Lü,Jiujun He,Mingzhu Liu,Can Wu,Yijing Liu,Xinyu Zhang,Zhen Liu
Nattokinase (NK) has been used as a new generation thrombolytic drug, due to its high safety, low cost and low side effects. However, it is sensitive to external environment and may lose the enzyme activity easily. Peptide dendrimer possesses functional groups on its surface, adjustable sizes, biodegradability, biocompatibility, and low toxicity, which could be used as ideal carrier for drug protection and delivery. Demonstrated for the first time in this paper, a PEGylated dendrimer (G n -PEG-G n ) composed of polyglutamic acid is designed and synthesized as delivery platform of NK for thrombus treatment. A panel of PEGylated dendrimers with three different generations of 2, 3, 4 was prepared to investigate the effect of dendrimer architecture on the properties and therapeutic efficacy of the resultant NK-loaded delivery systems in terms of the morphology, dimension and enzyme activity. The results demonstrated that the NK-loaded G 3 -PEG-G 3 (G 3 -PEG-G 3 /NK ratio of 6/1), of all the formulations, displayed the optimal enzyme activity for dissolving thrombus in vitro , thus offering great potential for the treatment of thrombus.
研究领域:
生物材料
·
药物递送
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POLYMERS FOR ADVANCED TECHNOLOGIES
·
2019
·Vol. 30
·期 9
·2353-2360
·
IF 2.162
Mengjie Huang,Shaoyu Lü,Yanzheng Ji,Zengqiang Wang,Shao-Fei Zhang,Taomei Qi,Jia Yan,Tao Li,Yongming Liu,Mingzhu Liu
Thrombosis has become one of the major diseases harmful to human health. The new-generation thrombolytic drug nattokinase (NK) has been used in the treatment of thrombosis because of its high safety, small side effects, and good thrombolytic effect. However, its application is limited because of its short half-life and inactivation in external environments. Therefore, it is necessary to retain the enzyme activity of NK to improve its environmental stability. In this study, NK was decorated by bonding peptide dendrimers to improve its enzymatic activity. Polyglutamic acid dendrimers of generation 2 were firstly synthesized, and then the targeting molecule arginine-glycine-aspartic acid (RGD) was linked to dendrimers by reaction of carboxyl and amino groups. Subsequently, polyglutamic dendrimer particles were bonded on the periphery of NK by chemical reaction and were used as carriers for NK. The carriers were characterized by Fourier transform infrared (FTIR) and thermogravimetric (TG) analysis, and their size and morphology were evaluated. Their enzyme activity at different pH and temperature was determined, and improved NK activity was achieved after bonding with dendrimers under acid and alkaline conditions and high temperature. Their thrombolytic properties were evaluated by in vitro and in vivo thrombolytic experiments. Effective thrombolytic effect was observed. This study indicated that the NK carrier prepared by chemical bonding may have applications in the treatment of thrombosis.
研究领域:
生物化学
·
药学
·
医学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2022
·Vol. 11
·期 16
·2200416
·
IF 11.092
Xingping Quan,Yan Han,Pengde Lu,Yuanfu Ding,Qingfu Wang,Yiyang Li,Jianwen Wei,Qiaoxian Huang,Ruibing Wang,Yonghua Zhao
Thromboembolic stroke is typically characterized by the activation of platelets, resulting in thrombus in the cerebral vascular system, leading to high morbidity and mortality globally. Intravenous thrombolysis by tissue plasminogen activator (tPA) administration within 4.5 h from the onset of symptoms is providing a standard therapeutic strategy for ischemic stroke, but this reagent simultaneously shows potential serious adverse effects, e.g., hemorrhagic transformation. Herein, a novel delivery platform based on Annexin V and platelet membrane is developed for tPA (APLT-PA) to enhance targeting efficiency, therapeutic effects, and reduce the risk of intracerebral hemorrhage in acute ischemic stroke. After preparation by extrusion of platelet membrane and subsequent insertion of Annexin V to liposomes, APLT-PA exhibits a high targeting efficiency to activated platelet in vitro and thrombosis site in vivo, due to the binding to phosphatidylserine (PS) and activated platelet membrane proteins. One dose of APLT-PA leads to obvious thrombolysis and significant improvement of neurological function within 7 days in mice with photochemically induced acute ischemic stroke. This study provides a novel, safe platelet-biomimetic nanomedicine for precise thrombolytic treatment of acute ischemic stroke, and offers new theories for the design and exploitation of cell-mimetic nanomedicine for diverse biomedical applications.
研究领域:
药剂学
·
神经科学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2021
·Vol. 33
·期 25
·2007073
·
IF 30.849
Qingyuan Wu,Fengrong Zhang,Xueting Pan,Zhijun Huang,Zhijie Zeng,Hongyu Wang,Jun Jiao,Xiaolu Xiong,Lixin Bai,Dongsheng Zhou,Huiyu Liu
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.
研究领域:
生物医学工程
·
纳米技术
·
超声治疗
·
溶栓
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）