{"title":"脂质体功能化生物相容性聚氨酯微球与细菌捕获陷阱的细菌感染的综合管理。","authors":"Ziyue Ling, Shifan Chen, Zhen Hu, Jianxu Bao, Chunji Jiang, Weifeng Zhao, Changsheng Zhao","doi":"10.1039/d5tb01907a","DOIUrl":null,"url":null,"abstract":"<p><p>Bacterial infections pose a significant threat to public health, as pathogens and their secreted toxins jointly activate immune responses, and severe cases may develop into sepsis. Effective anti-infective treatment requires comprehensive eradication of pathogens, involving not only bacterial clearance but also neutralization of virulence factors. Traditional adsorbents in blood purification often face a trade-off between efficacy and biosafety. Herein, we develop a graded modified hemoperfusion adsorbent for full-cycle sepsis management. Cationic diallyl dimethylammonium chloride (DDA)-modified carbon nanotubes (CNTs) are embedded within polyurethane precursors, and liposomes (Lipo) are anchored onto the surface of microspheres through polymer chain entanglement and electrostatic interactions during phase separation, resulting in polyurethane-CNT-DDA-Lipo (PUD-L) porous microspheres. This hierarchical modification strategy enables spatial partitioning, effectively balancing the material functionality with biosafety and achieving the simultaneous removal of bacteria and toxins. The porous surface of PUD-L matches the size of the bacteria, serving as a bacterial trap that removes 98.2% of <i>Staphylococcus aureus</i> (<i>S. aureus</i>) and 97.2% of <i>Escherichia coli</i> (<i>E. coli</i>) within 3 h. Additionally, PUD-L significantly decreases hemolysis induced by exotoxins (from 49.49% to 0.22%) and reduces endotoxin levels (from 236.08 EU per mL to 38.15 EU per mL), primarily through adsorption. In a sepsis blood model, treatment with PUD-L reduces pro-inflammatory cytokine concentrations to normal physiological levels. Overall, this work highlights that both pathogens and their toxins are key triggers of excessive inflammation. The PUD-L microspheres represent a promising strategy that integrates antibacterial activity and virulence factor adsorption in a hierarchical method while maintaining great biocompatibility, providing a novel platform for the comprehensive management of bacterial infections.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. 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Traditional adsorbents in blood purification often face a trade-off between efficacy and biosafety. Herein, we develop a graded modified hemoperfusion adsorbent for full-cycle sepsis management. Cationic diallyl dimethylammonium chloride (DDA)-modified carbon nanotubes (CNTs) are embedded within polyurethane precursors, and liposomes (Lipo) are anchored onto the surface of microspheres through polymer chain entanglement and electrostatic interactions during phase separation, resulting in polyurethane-CNT-DDA-Lipo (PUD-L) porous microspheres. This hierarchical modification strategy enables spatial partitioning, effectively balancing the material functionality with biosafety and achieving the simultaneous removal of bacteria and toxins. The porous surface of PUD-L matches the size of the bacteria, serving as a bacterial trap that removes 98.2% of <i>Staphylococcus aureus</i> (<i>S. aureus</i>) and 97.2% of <i>Escherichia coli</i> (<i>E. coli</i>) within 3 h. 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引用次数: 0
摘要
细菌感染对公共卫生构成重大威胁,因为病原体及其分泌的毒素共同激活免疫反应,严重的病例可能发展为败血症。有效的抗感染治疗需要全面根除病原体,不仅包括细菌清除,还包括毒力因子的中和。传统的吸附剂在血液净化中往往面临着有效性和生物安全性之间的权衡。在此,我们开发了一种分级改良的血液灌流吸附剂,用于脓毒症的全周期管理。阳离子二烯丙基二甲基氯化铵(DDA)修饰的碳纳米管(CNTs)嵌入聚氨酯前驱体中,脂质体(Lipo)在相分离过程中通过聚合物链缠结和静电相互作用固定在微球表面,形成聚氨酯- cnt -DDA-Lipo (PUD-L)多孔微球。这种分层修改策略实现了空间分区,有效地平衡了材料功能与生物安全性,并实现了细菌和毒素的同时去除。PUD-L的多孔表面与细菌的大小相匹配,作为一个细菌陷阱,在3小时内去除98.2%的金黄色葡萄球菌(S. aureus)和97.2%的大肠杆菌(E. coli)。此外,PUD-L主要通过吸附显著降低由外毒素引起的溶血(从49.49%降至0.22%)和内毒素水平(从236.08 EU / mL降至38.15 EU / mL)。在脓毒症血液模型中,用PUD-L治疗可使促炎细胞因子浓度降至正常生理水平。总的来说,这项工作强调病原体和它们的毒素都是过度炎症的关键触发因素。PUD-L微球是一种很有前途的策略,它将抗菌活性和毒力因子吸附在分层方法中结合起来,同时保持良好的生物相容性,为细菌感染的综合管理提供了一个新的平台。
Liposome-functionalized biocompatible polyurethane microspheres with bacteria-capturing traps for comprehensive management of bacterial infections.
Bacterial infections pose a significant threat to public health, as pathogens and their secreted toxins jointly activate immune responses, and severe cases may develop into sepsis. Effective anti-infective treatment requires comprehensive eradication of pathogens, involving not only bacterial clearance but also neutralization of virulence factors. Traditional adsorbents in blood purification often face a trade-off between efficacy and biosafety. Herein, we develop a graded modified hemoperfusion adsorbent for full-cycle sepsis management. Cationic diallyl dimethylammonium chloride (DDA)-modified carbon nanotubes (CNTs) are embedded within polyurethane precursors, and liposomes (Lipo) are anchored onto the surface of microspheres through polymer chain entanglement and electrostatic interactions during phase separation, resulting in polyurethane-CNT-DDA-Lipo (PUD-L) porous microspheres. This hierarchical modification strategy enables spatial partitioning, effectively balancing the material functionality with biosafety and achieving the simultaneous removal of bacteria and toxins. The porous surface of PUD-L matches the size of the bacteria, serving as a bacterial trap that removes 98.2% of Staphylococcus aureus (S. aureus) and 97.2% of Escherichia coli (E. coli) within 3 h. Additionally, PUD-L significantly decreases hemolysis induced by exotoxins (from 49.49% to 0.22%) and reduces endotoxin levels (from 236.08 EU per mL to 38.15 EU per mL), primarily through adsorption. In a sepsis blood model, treatment with PUD-L reduces pro-inflammatory cytokine concentrations to normal physiological levels. Overall, this work highlights that both pathogens and their toxins are key triggers of excessive inflammation. The PUD-L microspheres represent a promising strategy that integrates antibacterial activity and virulence factor adsorption in a hierarchical method while maintaining great biocompatibility, providing a novel platform for the comprehensive management of bacterial infections.