International Journal of Nanomedicine
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2023
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IF 8
Bo Hu,Ying Yan,Fei Tong,Long Xu,Jia Zhu,Guangtao Xu,Ruilin Shen
Background Lumbrokinase (LK) is an enzyme complex with antithrombotic, antioxidant, antitumor, and immunomodulatory effects. It has been extensively studied and used in clinical anti-tumor therapy. However, its half-life is short, its bioavailability is low, and its toxicity and side effects are great, which greatly limit its clinical application. Therefore, LK is often combined with other drugs (such as immune agents, hormones, or Chinese herbal medicine) to reduce its dosage and side effects and to improve its anti-tumor effects.Methods and results Here, we described an LK/paclitaxel (PTX) nanocarrier based on poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyoxycarbonyl-l-lysine)-r-poly(l-lysine)) (PEG-b-(PELG-g-(PZLL-r-PLL))). In the present study, LK and PTX were loaded by electrostatic and/or hydrophobic effects under mild conditions, thereby increasing the half-life and bioavailability of the drugs via the sustained release and enhancement of tumor site enrichment by the LK/PTX/PEG-b-(PELG-g-(PZLL-r-PLL)) complex through passive targeting. In this study, using bladder cancer cells (J82 cells) and rat bladder cancer model as the object, the structure of the nanocarrier, the relationship between drugs composition and antitumor properties were systematically studied.Conclusion We propose that the block copolymer PEG-b-(PELG-g-(PZLL-r-PLL)) may function as a potent nanocarrier for augmenting anti-bladder cancer pharmacotherapy, with unprecedented clinical benefits.
研究领域:
药学
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肿瘤学
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纳米技术
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生物医学工程
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2023
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IF 15.1
Meng Huang,Yuda Zhu,Guang Xin,Yilan Wang,Fan Li,Shiyi Li,Yuman Dong,Kun Zhang,Lijuan Feng,Li Tang,Boli Zhang,Wen Huang
Intravenous injection of thrombolytic drugs is the most feasible strategy for the clinical treatment of thrombotic diseases, however, its applications are yet limited by narrow therapeutic index, short half-life, and hemorrhagic risk. Inspired by the excessive ROS and inflammatory factors at the thrombus site, we manufactured a thrombus microenvironment-modulated nanosystem , which achieved the targeted delivery of thrombolytic drugs and ROS scavenging agents. Ir monomers (Ir-PVP) with enzyme-mimetic activity were prepared and then wrapped with lumbrokinase (LK) by HA materials of thrombo-inflammatory affinity, forming multifunctional thrombolytic agents [email protected] [email protected] could prolong the biological half-life of LK and target the thrombus site to release LK with reduced bleeding risk. Moreover, Ir-NPs, as both CT imaging contrast agent and ROS scavenger, not only allowed us to observe the progression of thrombolytic treatment through CT imaging in real time, but also played an important role in elimination of excessive ROS at thrombus site. Taken together, the in vitro and in vivo experiments illustrated that [email protected] with CT function displayed an excellent efficiency in thrombolysis, anti-inflammation and ROS scavenging. Our work may encourage further exploration of thrombus microenvironment-modulated theranostic platforms.
研究领域:
纳米医学
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诊疗学
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药学
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生物医学工程
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产品关联
DOI
高影响因子
BIOCHEMICAL ENGINEERING JOURNAL
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2016
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IF 2.463
Yunchang Fan,Xing Dong,Yingying Zhong,Jing Li,Juan Miao,Shaofeng Hua,Yan Li,Boyu Cheng,Wenqiong Chen
In this work, the hydrolysis of casein by lumbrokinase in the presence of ionic liquids (ILs) was studied. The experimental results indicated that the effects of ILs on the casein hydrolysis depended on their concentrations; at low IL concentration, the addition of ILs could remarkably increase the lumbrokinase activity due to enhancing the hydrophilicity of casein by forming the IL-casein complex. However, at higher IL concentration, significant decrease in lumbrokinase activity was observed because the presence of ILs disturbed the hydrogen bond network in the active site of lumbrokinase. At the IL concentrations beyond their critical micelle concentrations, the incorporation of substrate into the micellar pseudo-phase also contributed to the decrease in lumbrokinase activity. When a more hydrophilic substrate was adopted, the effects of ILs on the lumbrokinase activity were negative in all cases. Fluorescence analysis indicated that hydrogen bonding was the main driving force ruling the interaction of ILs and lumbrokinase.
研究领域:
生物化学
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酶学
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化学工程
✓ 已验证
产品关联
DOI
高影响因子
Asian Journal of Pharmaceutical Sciences
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2024
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IF 10.7
Mengying Cheng,Tianxiang Yue,Hong Wang,Lai Jiang,Qiaoling Huang,Fanzhu Li
Atherosclerosis (AS) is a progressive inflammatory disease, and thrombosis most probably leads to cardiovascular morbidity and mortality globally. Thrombolytic drugs alone cannot completely prevent thrombotic events, and treatments targeting thrombosis also need to regulate the inflammatory process. Based on the pathological process of AS dynamic development, biomimetic thrombus-targeted nanoparticles HMTL@PM were prepared. Hirudin and lumbrukinase, the effective substances of traditional Chinese medicine, were self-assembled under the action of tannic acid and Mn 2+ . HMTL@PM dissociated in the weakly acidic microenvironment of atherosclerosis and exhibited an excellent therapeutic effect of alleviating inflammation, dissolving thrombus, anticoagulation, and promoting cholesterol efflux. HMTL@PM effectively regulated the progression of AS and provided a new perspective for the development of drug delivery systems for AS therapy, which owned important research significance for reducing the mortality of cardiovascular and cerebrovascular diseases.
研究领域:
纳米技术
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药学
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心血管疾病
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治疗学
✓ 已验证
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
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2018
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IF 1.883
Jie Liao,Xiaoting Ren,Bowen Yang,Hou Li,Yuexin Zhang,Zongning Yin
Lumbrokinase (LK) has strong fibrinolytic and thrombolytic activities, but it has a short half-life, can be easily inactivated, and may cause hemorrhage as a side effect. This study develops a potential thrombolytic therapy by fabricating N,N,N-Trimethyl Chitosan (TMC) nanoparticles modified with the cyclic Arg-Gly-Asp-Phe-Lys peptide (c-RGD) and loaded with LK (i.e. c-RGD-LK-NPs). The binding of c-RGD to platelet membrane GPIIb/IIIa receptors is expected to enable targeted delivery of the c-RGD-conjugated TMC to the thrombus. The synthesized c-RGD-LK-NPs had a mean particle size of 232.0 nm, zeta potential of 19.8 mV, entrapment efficiency of 52.7% ± 2.5%, and loading efficiency of 17.4% ± 0.65%. Transmission electron microscopy showed that they were generally spherical. The c-RGD-LK-NPs gave a cumulative in vitro LK release of 80.6% over 8 h, and the activity of LK was close to 80%, indicating that the nanoparticles protected the activity of LK. In vitro blood clot lysis assays were carried out and in vivo thrombolysis effect was tested in Sprague-Dawley rats carotid artery thrombus model. In all cases, the c-RGD-LK-NPs showed superior performance compared with the free LK and the unmodified TMC nanoparticles loaded with LK. The c-RGD-LK-NPs reagent is expected to be potentially useful in treating thromboembolic diseases.
研究领域:
药学
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纳米技术
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治疗学
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血液学
✓ 已验证
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2017
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IF 6.216
Qing Chang,Long Liu,Yaseen Muhammad,Shaoxia Weng,Zhenfei Feng,Tengyou Wei,Jingling Lei,Zhangfa Tong,Zhenxia Zhao
A magnetic Fe-N doped hollow acicular porous carbon (FeN-HAPC) with dopamine was successfully fabricated using a green free template-removal strategy for Lumbrukinase (LK) immobilization. FeN-HAPC was characterized by SEM , TEM , XRD, N 2 adsorption, XPS and FT-IR. Results revealed that immobilized LK through adsorption on FeN-HAPC possessed high activity (350 U/mg), good reusability (∼80% of initial value after 7th usage), and storage stability (86.0% at 4 °C for 30 days). Moreover, dopamine modification of FeN-HAPC ( [email protected] ) further significantly enhanced the amount and adsorption affinity towards immobilized LK, and thus exhibiting higher enzyme activity (617.5 U/mg) and reusable performance (87.3% for the 7th usage), and storage stability (92.4% at 4 °C for 30 days). Its deactivation half-life was 6–14 times longer than those immobilized over conventional Fe 3 O 4 microsphere or free ones. The deactivation energy of [email protected] /STI-LK was 146 kJ/mol, much higher than free LK and Fe 3 O 4 @CTS/STI-LK samples. Thus, the composite prepared in this study, attributed to possessing hollow structures with magnetic characteristic, high specific surface area, and high dispersion of affinity sites can be deemed as a promising candidate for enzyme adsorptive immobilization in practical applications.
研究领域:
材料科学
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生物技术
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酶工程
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
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2020
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IF 7.242
Ying Wang,Xiaowen Xu,Xuan Zhao,Zongning Yin
Pathological thrombosis within a vessel hampers blood flow and is the mainspring of numerous fatal cardiovascular complications. In order to specifically image and dissolve a thrombus, we rationally designed a functionalized polymeric hybrid micelle (PHM) system self-assembled from amphiphilic polycaprolactone-polyethylenimine (PCL-PEI) and polycaprolactone-polyethylene glycol (PCL-PEG). Based on a biological component of thrombi, activated coagulation factor XIII (FXIIIa), which is responsible for fibrin crosslinking, we further developed FXIIIa-targeted near infrared imaging and thrombolytic nanoparticles , termed IR780/FPHM/LK NPs, through chemical conjugation of peptides to the system. In a ferric chloride (FeCl 3 )-induced mouse carotid thrombosis model, IR780/FPHM/LK NPs specifically targeted the thrombus and significantly enhanced the photoacoustic signal for an accurate diagnosis. When loaded with the fibrinolytic drug lumbrokinase (LK), FPHM remarkably dissociated the thrombus accompanied by an increase in the d -dimer level, a fibrin degradation product , and alleviation of fatal nonspecific hemorrhagic risk. Given its thrombus-specific imaging along with potent therapeutic activities, IR780/FPHM/LK NPs hold promise for developing nanotheranostic agents in preclinical thrombotic vascular disease models.
研究领域:
纳米技术
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诊疗学
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心血管疾病
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2018
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IF 3.997
Mingbo Ji,Xiangrong Chen,Jianquan Luo,Yinhua Wan
Two anticoagulant proteins, nattokinase and lumbrokinase, were successfully immobilized onto the dopamine-coated polysulfone (PSf) membrane surface by covalent bonding. X-ray photoelectron spectroscopy (XPS) and Zeta potential measurement confirmed the immobilization of these anticoagulant proteins. The immobilization yield of nattokinase and lumbrokinase reached to 35.2 and 33.4 μg/cm 2 , respectively. The water contact angle measurement revealed that the membrane surface hydrophilicity was improved after immobilizing the anticoagulant proteins. Meanwhile, the immobilized proteins retained their biological activity. Then blood compatible tests demonstrated that the modified membranes had lower static protein adsorption, platelet/erythrocyte adhesion, hemolysis, as well as longer blood clotting time, compared to virgin PSf membrane. In addition, the nattokinase-immobilized membrane showed a higher blood compatibility than BSA and lumbrokinase immobilized memrbanes, due to its’ high bioactivity. Our research demonstrates that the dopamine-assisted immobilization of nattokinase and lumbrokinase can endow the membranes with improved blood compatibility as well as high biological activity, which may be expected to apply to blood-contacting materials.
研究领域:
生物材料
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生物医学工程
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血液相容性
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2024
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IF 6.7
Liming Liu,Ning Ma,Lu Wang,Yu Zhang,Yi-Zhen Wan,Tianze Wang,Weiping Qian
Fibrinolytic activity assay is particularly important for the detection, diagnosis, and treatment of cardiovascular disease and the development of fibrinolytic drugs. A novel efficacious strategy for real-time and label-free dynamic detection of fibrinolytic activity based on ordered porous layer interferometry (OPLI) was developed. Fibrin or a mixture of fibrin and plasminogen (Plg) was loaded into the highly ordered silica colloidal crystal (SCC) film scaffold to construct a fibrinolytic response interference layer to measure fibrinolytic activity with different mechanisms of action. Fibrinolytic enzyme-triggered fibrinolysis led to the migration of interference fringes in the interferogram, which could be represented by optical thickness changes (ΔOT) tracked in real time by the OPLI system. The morphology and optical property of the fibrinolytic response interference layer were characterized, and the Plg content in the fibrinolytic response interference layer and experimental parameters of the system were optimized. The method showed adequate sensitivity for the fibrinolytic activity of lumbrokinase and streptokinase, with wide linear ranges of 12–6000 and 10–2000 U/mL, respectively. Compared with the traditional fibrin plate method, it has a lower detection limit and higher linearity. The whole kinetic process of fibrinolysis by these two fibrinolytic drug models was recorded in real time, and the Michaelis constant and apparent kinetic parameters were calculated. Importantly, some other blood proteins were less interfering with this system, and it showed reliability in fibrin activity detection in real whole blood samples. This study established a better and more targeted research method of in vitro fibrinolysis and provided dynamic monitoring data for the analysis of fibrinolytic activity of whole blood.
研究领域:
生物医学工程
·
心血管疾病
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药物开发
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干涉测量
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纤溶
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）