A Guanosine-Quadruplex Hydrogel as Cascade Reaction Container Consuming Endogenous Glucose for Infected Wound Treatment-A Study in Diabetic Mice.
A Guanosine-Quadruplex Hydrogel as Cascade Reaction Container Consuming Endogenous Glucose for Infected Wound Treatment-A Study in Diabetic Mice.
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DOI：
10.1002/advs.202103485
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Busscher HJ
中科院分区：
文献类型：
--
作者：
Li Y;Su L;Zhang Y;Liu Y;Huang F;Ren Y;An Y;Shi L;van der Mei HC;Busscher HJ
感染抗生素耐药细菌的糖尿病足溃疡是糖尿病的严重并发症。载有抗菌药物的水凝胶被用作感染伤口的敷料，但抗菌药物耐药性感染数量的持续增加需要新的、非抗生素的设计。在这里，设计了由鸟苷、2-甲酰基苯基硼酸和腐胺组成的鸟苷四联体（G4）水凝胶，并将其用作级联反应容器。 G4-水凝胶负载有葡萄糖氧化酶和氯高铁血红素。第一个级联反应由葡萄糖氧化酶引发，将葡萄糖和 O2 转化为葡萄糖酸和 H2O2。在体外，这种反应对杀死悬浮液中的金黄色葡萄球菌或铜绿假单胞菌影响最大，但对生物膜生长模式下的细菌的杀灭作用有限。然而，第二个级联反应将 H2O2 转化为活性氧 (ROS)，由于氯化血红素渗透到生物膜中并与生物膜基质中的 eDNA G-四链体相互作用，也增强了对生物膜细菌的杀灭作用。因此，第二级联反应产生接近目标细菌的ROS，尽管ROS的寿命很短，但仍有助于杀死细菌。与临床上常见的环丙沙星冲洗相比，这些 G4 水凝胶覆盖糖尿病小鼠感染伤口的愈合速度更快。此外，感染伤口周围的局部葡萄糖浓度降低。总之，负载葡萄糖氧化酶和氯高铁血红素的 G4 水凝胶是感染伤口敷料的良好候选者，特别是糖尿病患者。含有葡萄糖氧化酶和氯化血红素的超分子鸟苷四联体（G4）水凝胶提供了适合作为感染伤口抗菌敷料的级联反应容器。 G4-水凝胶中的级联反应利用内源性葡萄糖在感染性生物膜内产生活性氧，在非抗生素的基础上杀死多重耐药细菌，加快感染伤口的愈合，并降低糖尿病小鼠的局部葡萄糖水平。
Diabetic foot ulcers infected with antibiotic‐resistant bacteria form a severe complication of diabetes. Antimicrobial‐loaded hydrogels are used as a dressing for infected wounds, but the ongoing rise in the number of antimicrobial‐resistant infections necessitates new, nonantibiotic based designs. Here, a guanosine‐quadruplex (G4)‐hydrogel composed of guanosine, 2‐formylphenylboronic acid, and putrescine is designed and used as a cascade‐reaction container. The G4‐hydrogel is loaded with glucose‐oxidase and hemin. The first cascade‐reaction, initiated by glucose‐oxidase, transforms glucose and O2 into gluconic acid and H2O2. In vitro, this reaction is most influential on killing Staphylococcus aureus or Pseudomonas aeruginosa in suspension, but showed limited killing of bacteria in biofilm‐modes of growth. The second cascade‐reaction, however, transforming H2O2 into reactive‐oxygen‐species (ROS), also enhances killing of biofilm bacteria due to hemin penetration into biofilms and interaction with eDNA G‐quadruplexes in the biofilm matrix. Therewith, the second cascade‐reaction generates ROS close to the target bacteria, facilitating killing despite the short life‐time of ROS. Healing of infected wounds in diabetic mice proceeds faster upon coverage by these G4‐hydrogels than by clinically common ciprofloxacin irrigation. Moreover, local glucose concentrations around infected wounds decrease. Concluding, a G4‐hydrogel loaded with glucose‐oxidase and hemin is a good candidate for infected wound dressings, particularly in diabetic patients. A supramolecular guanosine‐quadruplex (G4)‐hydrogel containing glucose oxidase and hemin provides a cascade‐reaction container suitable as an antibacterial dressing for infected wounds. The cascade‐reaction in the G4‐hydrogel generates reactive‐oxygen‐species inside an infectious biofilm from endogenous glucose, killing multidrug resistant bacteria on a nonantibiotic basis, yielding faster healing of infected wounds, and reducing local glucose levels in diabetic mice.
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影响因子：
3.7
作者：
Neut D;Tijdens-Creusen EJ;Bulstra SK;van der Mei HC;Busscher HJ
通讯作者：
Busscher HJ
影响因子：
3.7
作者：
Dowd SE;Wolcott RD;Sun Y;McKeehan T;Smith E;Rhoads D
通讯作者：
Rhoads D
DOI：
10.1002/jbm.b.32800
发表时间：
2012-11-01
影响因子：
3.4
作者：
Lin, Yu-Hsin;Lin, Jui-Hsiang;Tseng, Guan-Chin
通讯作者：
Tseng, Guan-Chin
影响因子：
7.4
作者：
Ge, Chenchen;Luo, Quan;Zeng, Lingwen
通讯作者：
Zeng, Lingwen
由鸟苷、氨基糖苷和双功能锚组装而成的具有抗菌活性的刺激响应水凝胶。
影响因子：
10
作者：
Hu, Jingjing;Hu, Qianyu;Zhang, Yadong
通讯作者：
Zhang, Yadong