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RSC Advances · 2015 ·Vol. 5 ·期 71 ·58032-58040 · IF 3.84

Bionic design for anticoagulant surface via synthesized biological macromolecules with heparin-like chains

Fen Ran,Haiming Song,Jiayu Wu,Lang Ma,Xiaoqin Niu,Huili Fan,Long Kang,Changsheng Zhao

While polyethersulfone (PES) represents outstanding oxidative, thermal and hydrolytic stability as well as good mechanical and film-forming properties, the hemocompatibility of PES membranes must be dramatically enhanced to reduce injections of anticoagulants during hemodialysis. In this study, a series of biological macromolecules with heparin-like chains were synthesized via reversible addition fragmentation chain transfer (RAFT) polymerization to design anticoagulant membrane surfaces. When the synthesized copolymers were used as additives to modify the PES membrane using the phase separation method, the functional groups of the copolymers migrated and formed a negatively charged coating on the membrane surface. The modified PES membrane blended with a heparin-like block copolymer showed prolonged blood coagulation time and thereby good hemocompatibility. In addition, the clotting time of the modified membrane was enhanced with increasing amounts of the heparin-like amphiphilic tri-block copolymer. Furthermore, the results of the cell morphology and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay suggest that the cytocompatibility increases due to the addition of heparin-like additives. Thus, the heparin-like surface modification method seemed to be a promising approach for application in the biomedical field.

研究领域: 生物材料 · 医学工程
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JOURNAL OF MOLECULAR STRUCTURE · 2025 · IF 4.7

Colorimetric and luminescent determination of heparin based on assembly between a highly charged iridium(III) complex and gold nanoparticles

Jinshan Lin,Shengjie Wang,Pengchong Jiao,Mei-Jin Li

A highly charged water-soluble iridium(III) (Ir(III)) complex [(ppy) 2 Ir(bpy-N)] 3+ was designed, synthesized and characterized, and the crystal structure of it was determined by X-ray crystallography. The photophysical properties of complex in absence or presence of sodium heparin were studied by UV–vis absorption and photoluminescent spectroscopies. After addition of sodium heparin, the luminescent intensity of complex at ca. 656 nm was increased about 4.3-fold, without any observable color change in the solution. The new Ir(III) complex was also assembled with gold nanoparticles (AuNPs) for the dual-mode detection of sodium heparin, combined with colorimetric and luminescent methods. In this system, the luminescence of complex was quenched by AuNPs firstly with the red color of gold nano colloids transition into blue due to the aggregation. The color of the assembled system changed from blue to purple to red accompanying with the luminescent intensity of system restoring after increasing the concentrations of added sodium heparin. The sodium heparin was sensitively detected with LOD of 0.09 μg/mL. This work demonstrates a novel bifunctional sensing platform for sodium heparin, leveraging the unique photophysical properties of the Ir(III) complex and the plasmonic behavior of AuNPs, offering significant potential for sensitive and visual detection applications.

CAS / MDL: 9041-08-1
研究领域: 分析化学 · 纳米医学 · 药物分析
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Photoresponsive protamine ionic complex towards a smart hemostatic biomaterial

Yun Liu,Guoqiang Zhang,Jia Chen,Ziying Zhang,Quanxin Wu,Lei Zhang,Shanhui Zhu,Qikai Liang,Zhongtao Wu,Xiliang Luo,Zhen Wang,Weishen Zeng

Protamine (PA) is the only licensed antidote for reversing heparin anticoagulation by electrostatically binding with heparin. Efforts have been made on designing various heparin-scavengers, while, it remains a great challenge for gaining the external-stimuli responsive PA-release material. In this study, a generic strategy is developed for fabricating photoresponsive protein materials with the designed azobenzene-containing surfactant. For the first time, based on the isomerization of azobenzene, both cationic and anionic proteins could be phase change biomaterials which are capable of transiting to isotropic state under UV irradiation at room temperature. The formation of isotropic state could set the proteins free from the binding state, activating their intrinsic biological functions. Employing this mechanism, one smart PA material for inhibiting heparin is developed, which could effectively photo-modulate the heparin concentration by turning on-and-off the free state of PA from the binding state. With good biocompatibility, the PA material addresses photoresponsive hemostatic activity in biological studies, confirming its great potential clinical values. This work provides a new designing strategy for gaining photocontrollable hemostasis materials, also opening new opportunities for developing photoresponsive protein drugs and biomedical materials.

研究领域: 生物医学工程 · 材料科学 · 药物开发
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CATALYSIS LETTERS · 2021 ·Vol. 151 ·期 9 ·2537-2546 · IF 3.186

Peroxidase Mimicking Activity of Palladium Nanocluster Altered by Heparin

Zhang Qianqian,Zheng Shanshan,Zhang Jinli,Li Wei,Fu Yan

NADH, composed of metal binding, charged and redox groups, acts as a “three-in-one” template to construct peroxidase mimicking Pd nanoclusters (NCs). The physicochemical properties of Pd NCs are highly dependent upon the molar ratio of [NADH]/[Na 2 PdCl 4 ], thereby contributing to distinct peroxidase mimicking activities. The ultrasmall Pd nanozyme that contains 30% metallic Pd 0 species, exhibits the K m of 0.063 mM toward TMB and 80.8 mM toward H 2 O 2 . Notably, addition of heparin enables the enhancement of its peroxidase-like activity in neutral media. A colorimetric assay was well-established at pH 6 for quantitatively monitoring heparin in aqueous solution and biological fluid. The linear response lies in the range of 0.5–25 µg mL −1 , with the limit of detection of 1.1 ng mL −1 . This work paves a promising pathway to manufacture highly active enzyme mimetics with desirable physicochemical properties. Graphic Abstract

研究领域: 生物化学 · 纳米医学 · 分析化学
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Hydrophobic-modified heparin coatings with adaptively anti-thrombotic and anti-bacterial functions for interventional cardiovascular catheters

Xu Zhang,Mingzhe Wang,Lin Liu,Huan Yu,Yang Liu,Xiaozheng Duan,Lei Wang,Hengchong Shi,Shifang Luan

Interventional cardiovascular catheters (ICCs) are prone to complications such as venous thrombosis and occlusion during clinical applications, primarily due to the gradual adhesion and accumulation of cells, proteins, and microorganisms on their surfaces. Heparin sodium (HS) represents a typical clinically antithrombotic agent, whereas its hydrophilicity usually limits stable binding to hydrophobic catheter surfaces. Herein, we propose an easy-operating one-step strategy for fabricating hydrophobic-modified heparin based on electrostatic assembly between ethyl lauroyl arginate (ELA), a cationic antimicrobial compound, and anionic HS. The resulting ELA-HS complex shows water-insoluble and alcohol-soluble features, which can form a uniform and robust coating driven by electrostatic and hydrophobic interactions upon a series of catheters with diverse shapes and multi-cavity structures via solvent immersion. Molecular dynamics (MD) simulation elucidated the formation mechanism of hydrophobic-modified heparin, as well as the assembly mechanism between the coating and substrates. Importantly, this obtained ELA-HS coating with adaptive dissociation effectively resists the adsorption of fibrinogen and significantly reduces the adhesion of blood cells, including platelets, lymphocytes, and monocytes. Leveraging ELA’s inherent bactericidal properties, the coating also demonstrates substantial antibacterial efficacy, reducing bacterial colonization by over 99% whether gram-negative Escherichia coli ( E.coli. ) and gram-positive Staphylococcus aureus ( Sa. ). In vivo validation further confirms the coating’s dual functionality in preventing thrombosis and microbial infection, even in stringent acute models of canine jugular vein implantation. This ELA-HS modification strategy offers a practical solution to enhance the hemocompatibility and infection resistance of interventional catheters, addressing critical clinical challenges associated with thrombosis and bacterial adhesion.

CAS / MDL: 9041-08-1
研究领域: 生物医学工程 · 材料科学 · 心血管医学
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CARBOHYDRATE POLYMERS · 2019 · IF 6.044

Glycosaminoglycan / gold nanocluster hybrid nanoparticles as a new sensing platform: Metastatic potential assessment of cancer cells

Xiqi Ma,Xiaojuan Wang,Qi Chen,Hua He,Yixin Sun,Hui Liu,Yanan Wang,Jianbo Qu,Fang Huang

A novel fluorescent heparanase assay based on hybrid nano-assembly of gold nanocluster and glycosaminoglycan is developed. The nanoparticle probes are fabricated through the co-assembly of positively charged gold nanoclusters with negatively charged heparin molecules, which is accompanied by a dramatic size change and a 2.5-fold fluorescence enhancement. It is demonstrated that the fluorescence enhancement is due to denser aggregation of Au-thiolate complexes in the hybrid nanoparticle and the fluctuation of the fluorescence intensity is an indicator of the variation in assembly efficiency. Experiments in solution and in cell lysis media showed that the heparanase could turn-off the fluorescence with a high selectivity, which could be utilized for the assessment of heparanase activity and the metastatic potentials of different tumour cells. This assay technique is low cost, easy to prepare, and showing good performance. The co-assembly strategy has potential to be transferable to construct other functional nanomaterial.

CAS / MDL: 9007-28-7 39455-18-0
研究领域: 生物化学 · 纳米医学 · 癌症研究
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ACS Biomaterials Science & Engineering · 2016 · IF 0

Covalent Bonding of Heparin on the Crystallized Poly(lactic acid) (PLA) Membrane to Improve Hemocompability via Surface Cross-Linking and Glycidyl Ether Reaction

Zhu Xiong,Fu Liu,Haibo Lin,Jinglong Li,Yi Wang

The hemocompatibility of the dialysis membrane has been considered the key factor influencing the dialysis performance for curing the kidney malfunction. In this work, the commonly used anticoagulant heparin in the clinic was directly bonded to the poly(lactic acid) (PLA) membrane to improve the hemocompatibility via the glycidyl ether reaction. A novel precopolymer P(VP-VTES-GMA) was first prepared via free radical polymerization. The surface cross-linking of the precopolymer containing GMA segments enabled the membrane to anchor heparin through the glycidyl ether reaction. The chemical structure of the precopolymer was confirmed by 1H NMR. The surface chemistry was analyzed by XPS, toluidine blue staining, and solubility tests. The crystallization behavior, heat resistance, morphology, hydrophilicity, pore size, and pure water flux were investigated. The hemocompatibility was comprehensively investigated via APTT, PRT, PT, FIB, and platelet adhesion tests. The simulated dialysis performances relating to urea, creatinine, lysozyme, and BSA clearance were measured. All results demonstrated that the covalent bonding of heparin provided the PLA membrane with excellent hemcompatibility, hydrophilicity, heat resistance, and dialysis performance as well.

研究领域: 生物医学工程 · 材料科学
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ChemElectroChem · 2017 ·Vol. 4 ·期 3 ·472-475 · IF 4.136

A Peptide-Based Electrochemical Biosensor for Facile Measurement of Whole-Blood Heparin

Fanyu Meng,Weiguo Liang,Haixuan Sun,Ligang Wu,Xiao Gong,Peng Miao

Graphical Peptide–heparin composites : A simple electrochemical approach for the determination of heparin level in human whole-blood is developed based on specific peptide recognition (see picture). The first peptide-based electrochemical biosensor for the measurement of the anti-coagulant heparin using electrochemical impedance spectroscopy is reported. The peptide immobilized on the electrode interface specially captures heparin with high affinity. The composites formed on the electrode can thus effectively repel electrochemical species, leading to an increase in interfacial charge transfer resistance. After analyzing the electrochemical signals, a linear detection range from 0.05 to 10.0 μg/mL is obtained. The detection limit is calculated to be 0.01 μg/mL, which is extremely low with such a simple sensing mechanism. Moreover, the proposed method has potential application for sensitive and separation-free detection of heparin in whole-blood samples.

研究领域: 生物化学 · 医学检测 · 电化学
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RSC Advances · 2015 ·Vol. 5 ·期 21 ·16368-16375 · IF 3.84

Facile synthesis of biocompatible N, S-doped carbon dots for cell imaging and ion detecting

Yupeng Sun,Chen Shen,Jing Wang,Yun Lu

A facile, simple, effective and green method has been developed to synthesize nitrogen and sulfur co-doped carbon dots (N, S-CDs) from heparin sodium. The as-prepared N, S-CDs possess naked-eye observable blue-green luminescence, good biocompatibility, low toxicity and strong fluorescence in live cell imaging, indicating their great potential to serve as high quality optical imaging probes. Besides, the N, S-CDs can also be used as a competitive fluorescent sensing platform for the detection of Fe3+.

CAS / MDL: 9041-08-1
研究领域: 生物医学工程 · 材料科学 · 分析化学
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Materials Science & Engineering C-Materials for Biological Applications · 2018 · IF 5.08

Designing heparan sulfate-based biocompatible polymers and their application for intracellular stimuli-sensitive drug delivery

Lipeng Qiu,Lu Ge,Miaomiao Long,Qian Wang,Yan Zhang,Xiaotian Shan,Jingxiao Chen,Huijie Zhang,Xiaomei Li,Guozhong Lv,Jinghua Chen

Heparan sulfate (HS) is a kind of natural polysaccharides with good biocompatibility. And as drug carriers, it has some advantages compared to heparin. However, the preparation of HS is cumbersome and difficult, which limits its application in drug delivery. Here, we use modern separation technique combined with chromatography to establish a new preparation method of HS. The molecular weight and degree of dispersion of HS were (1.03 × 10 4  ± 107) kDa and 1.106, respectively. HS also showed low anticoagulation activity in comparison with heparin. Subsequently, novel redox-sensitive heparan sulfate-cystamine-vitamin E succinate (HS-SS-VES, HSV) micelles were designed to increase tumor selectivity and improve the therapeutic effect of doxorubicin (DOX). DOX-loaded HSV micelles (DOX/HSV) with spherical morphology had average particle size of 90–120 nm and good redox-triggered release behavior. The cell viabilities of blank micelles were >90% in both human breast cancer (MCF7) cells and African green monkey SV40-transformed kidney fibroblast (COS7) cells. However, the cytotoxicity of DOX/HSV in MCF7 cells was higher than that of COS7 cells. Flow cytometry analyses and confocal laser scanning microscopy observation indicated that DOX/HSV micelles were internalized by endocytosis, and then the drug was released quickly and entered the nuclei of tumor cells. The results demonstrate that high-purity HS can be prepared and has the potential to be further used for drug delivery in antitumor applications.

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 生物材料学 · 药剂学 · 肿瘤学
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2014 · IF 3.552

Route to hemocompatible polyethersulfone membranes via surface aminolysis and heparinization

Linghui Wang,Yu Cai,Yihang Jing,Baoku Zhu,Liping Zhu,Youyi Xu

Polyethersulfone (PES) membranes with improved hemocompatibility were prepared via solid–liquid interface aminolysis and heparinization. Reactive amino groups were generated by immersing solid PES membranes in proper diamine solution. Heparin was covalent immobilized on the surface via amide bond. The feasibility of surface aminolysis for the introduction of amino groups and the effectiveness for further heparin immobilization were confirmed by surface group analysis. The effect of aminolysis time on surface amino group concentration and bulk mechanical properties was investigated. The surface amino group concentration determined the amount and bioactivity of immobilized heparin chains. SEM images suggested that both the aminolysis and heparinization reaction had little effect on the surface morphology of PES membranes. Contact angle measurement, surface charge analysis, protein and platelet adsorption/adhesion experiment were applied to study the surface properties. The results showed that the heparinized PES membranes displayed enhanced hydrophilicity and hemocompatibility, indicating potential application in blood purification and other blood contacting fields.

CAS / MDL: 25952-53-8 92-31-9
研究领域: 生物医学工程 · 材料科学
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JOURNAL OF WUHAN UNIVERSITY OF TECHNOLOGY-MATERIALS SCIENCE EDITION · 2014 ·Vol. 29 ·期 5 ·1071-1077 · IF 0.422

Microwave-assisted immobilization of heparin onto polyurethane surface for improving blood compatibility

Qiu Bingsong,Mai Weizhong,Zeng Rong,Tu Mei,Zhao Jianhao,Zha Zhengang

Heparin was covalently immobilized onto polyurethane surface via a PEG spacer by a microwave-assisted approach to improve blood compatibility. Firstly, amino-terminated poly(ethylene glycol) (APEG) was rapidly grafted onto PU surface within 20 min by a two-step method involving microwave-assisted MDI-functionalization and subsequent microwave-assisted APEG coupling. Then, heparin was covalently immobilized through an amide linkage by the direct coupling of the carboxylic acid of heparin with the amino group of APEG on PU surface using carbodiimide coupling reaction. The surface structure and properties were characterized by X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and water contact angle measurements. The results revealed that heparin-immobilized PU surface had slightly increased roughness and significantly improved hydrophilicity in comparison to the original PU surface. The anticoagulant activity of films was evaluated by whole blood clotting time (CT) and prothrombin time (PT). Complement activation was assessed by detecting complement fragment 3a concentrations of serum exposed to the films. The results revealed that the microwave-assisted heparin-immobilized PU films had excellent antithrombogenicity and suppressed complement activation, indicating improved blood compatibility.

研究领域: 生物医学工程 · 材料科学
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