Acta Biomaterialia
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2022
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IF 10.633
Zhoujun Wang,Rui Yuan,Peiyang Li,Yanping Huang,Weifeng Zhao,Changsheng Zhao
Hyperkalemia is a common metabolic problem in patients with chronic kidney disease. Although oral medications and hemodialysis are clinically applied for lowering serum potassium , the intrinsic limitations encourage alternative therapy in the trend of adsorbent-based miniaturized blood purification devices. Cells serve as the biological K + storage units that accumulate K + through multiple mechanisms. Inspired by cells, our strategy aims at favorable permeation and enrichment of K + in the microsphere . We incorporate cation-affinitive groups into core-shell structures with submicron-sized phase separation. These nano-spaced side-groups cooperate to form interlinked clusters, where crown ethers with Angstrom-scale ring for size-matched complexation, while ionic sulfonic acid groups for hydrophilicity and charge-buffering. The unique structure with such non-covalent interactions facilitates K + for permeation across the shell and binding to the core while also ensuring mechanical strength and anti-swelling durability in biofluids. The microspheres exhibit high selectivity ratios of K + ( S K/Na , S K/Ca , S K/Mg up to 9.8, 21.6, and 17.7). As column adsorbents for hemoperfusion simulation, they effectively lower elevated K + levels to the normal range (clearance rates up to 44.4%/45.3% for hyperkalemic human serum/blood). Blood compatibility tests show low protein adsorption , preferable hemocyte compatibility, and anticoagulation property in vitro. This promising strategy has clinical potential for hyperkalemia in high-risk patients. Statement of significance Hyperkalemia (serum potassium >5 mmol/L) is a common complication in chronic renal failure patients. The limitations of existing treatments prompt a shift to wearable artificial kidney technology for clinical convenience and efficacy. Existing treatments have limitations, and we turn to adsorbent-based miniaturized blood purification devices in the prospect of wearable artificial kidney technology. There exists a lack of ion-specific adsorbents applied in extracorporeal circuits to redress electrolyte imbalances like hyperkalemia. Inspired by cells, we aim at the favorable permeation and enrichment of K + by microspheres. The microspheres have a microphase-isolated core-shell structure, whose nano-spaced groups form cation-affinitive clusters. Selective K + removal and blood compatibility are achieved. We expect this strategy to enlighten alternative hyperkalemia therapy for these high-risk patients.
研究领域:
生物医学工程
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材料科学
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肾脏病学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2020
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IF 8.724
Zhoujun Wang,Wei Sun,Zhiwei Wei,Jianxu Bao,Xin Song,Yupei Li,Haifeng Ji,Jue Zhang,Chao He,Baihai Su,Weifeng Zhao,Changsheng Zhao
Patients with chronic kidney disease are at high risk of hyperkalemia that is associated with various life-threatening complications. Treatments primarily rely on orally administered potassium binding agents, along with low curative effects and various side effects. Herein, direct serum potassium uptake was realized via zeolite–heparin-mimicking-polymer hybrid microbeads. The preparation process involved the synthesis of the heparin-mimicking polymer via the in situ cross-linking polymerization of acrylic acid and N -vinylpyrrolidone in polyethersulfone solution, the fabrication of microbeads via zeolite-mixing, electro-spraying and phase-inversion, and the subsequent aqueous-phase modifications based on ion-exchange and metal-leaching. An ultra-high (about 88%) amount of zeolite could be incorporated and well locked inside the polymer matrix. Potassium uptake capability was verified in water, normal saline and human serum, showing high selectivity and fast adsorption. The microbeads exhibited satisfying blood compatibility, negligible hemolysis ratio, prolonged clotting time, inhibited contact activation, and enhanced antifouling property toward serum proteins and cells. The proposed approach toward zeolite–heparin-mimicking-polymer hybrid microbeads provided a cheap, efficient and safe treatment protocol of hyperkalemia for the high-risk patients.
研究领域:
生物医学工程
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材料科学
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肾脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
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2019
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IF 8.063
Xiangjun Zhang,Qian Cheng,Lanlan Li,Liqing Shangguan,Chenwen Li,Shengke Li,Feihe Huang,Jianxiang Zhang,Ruibing Wang
Succinylcholine (Sch) is the only depolarizing neuromuscular blocking agent widely used for rapid sequence induction in emergency rooms. Unfortunately, a variety of (sometimes lethal) adverse effects, such as hyperkalemia and cardiac arrest, are associated with its use, and currently there are no specific antidotes to reverse Sch or to treat these side-effects. Methods: The binding behaviors of Sch and several synthetic receptors, including cucurbit[7]uril, sulfo-calix[4]arene and water-soluble carboxylatopillar[6]arene (WP[6]), were first investigated. With a mouse model, a leathal dose of Sch was selected for evaluation of the antidotal effects of these synthetic receptors on Sch induced mortality. The antidotal effects of a selected synthetic receptor, WP[6], on Sch induced cardiac arrhythmias, hyperkalemia, rhabdomyolysis and paralysis were subsequently evaluated with rat and mouse models. The reversal mechanism was also investigated at a cellular level. Results: All of these macrocyclic molecules exhibited relatively high binding affinities with Sch in vitro . In a Sch-overdosed mouse model, immediate injection of these synthetic receptors right after Sch administration increased the overall survival rate, with WP[6] standing out with the most effective antidotal effects. In addition, administration of WP[6] also reversed the paralysis induced by Sch in a mouse model. Moreover, infusion of WP[6] to Sch-overdosed rats reduced the incidence of cardiac arrhythmia, inhibited the otherwise abnormally high serum potassium levels, and relieved the muscular damage. At the cellular level, WP[6] reversed the Sch induced depolarization and reduced the efflux of intracellular potassium. Conclusion: Synthetic receptors, particularly WP[6], exhibited high binding affinities towards Sch, and presented a significant potential as supramolecular therapeutics to treat the various side effects of Sch by specifically sequestering Sch in vivo .
研究领域:
药理学
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药物化学
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治疗学
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DOI
PubMed
高影响因子
Soft Matter
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2023
·Vol. 19
·期 26
·4880-4890
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IF 3.4
Yan-Lin Wang,Xi Wang,Hai-Rong Yu,Ting Liang,Xing-Bin Lv,Chang-Jing Cheng
Potassium ions (K+) play crucial roles in many biological processes. Abnormal K+ levels in the body are usually associated with physiological disorders or diseases, and thus, developing K+-sensitive sensors/devices is of great importance for disease diagnosis and health monitoring. Herein, we report a K+-sensitive photonic crystal hydrogel (PCH) sensor with bright structural colors for efficient monitoring of serum potassium. This PCH sensor consists of a poly(acrylamide-co-N-isopropylacrylamide-co-benzo-15-crown-5-acrylamide) (PANBC) smart hydrogel with embedded Fe3O4 colloidal photonic crystals (CPCs), which could strongly diffract visible light and endow the hydrogel with brilliant structural colors. The rich 15-crown-5 (15C5) units appended on the polymer backbone could selectively bind K+ ions to form stable 2 : 1 [15C5]2/K+ supramolecular complexes. These bis-bidentate complexes served as physical crosslinkers to crosslink the hydrogel and contracted its volume, and thus reduced the lattice spacing of Fe3O4 CPCs and blue-shifted the light diffraction, and finally reported on the K+ concentrations by a color change of the PCH. Our fabricated PCH sensor possessed high K+ selectivity and pH- and thermo-sensitive response performances to K+. Most interestingly, the K+-responding PANBC PCH sensor could be conveniently regenerated via simple alternate flushing with hot/cold water due to the excellent thermosensitivity of the introduced PNIPAM moieties into the hydrogel. Such a PCH sensor provides a simple, low-cost and efficient strategy for visualized monitoring of hyperkalemia/hypokalemia, which will significantly promote the development of biosensors.
研究领域:
生物传感器
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材料科学
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分析化学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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