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Gelatinase-responsive release of an antibacterial photodynamic peptide against Staphylococcus aureus

机译:抗菌光动力肽对葡萄球菌的抗菌光动力学肽的凝胶酶响应释放

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摘要

Staphylococcus aureus (S. aureus) related staphylococcal infection is one of the most common types of hospital-acquired infections, which requires selective and effective treatment in clinical practice. Considering gelatinase as a characteristic feature of S. aureus, gelatinase-responsive release of the antibiotic reagent thereby can target the pathogenic S. aureus while sparing beneficial bacteria in the microflora. In this work, we design a hybrid antibacterial photodynamic peptide (APP, Ce6-GKRWWKWWRRPLGVRGC) based on the polycationic antimicrobial peptide GKRWWKWWRR by introducing a photosensitizer chlorin e6 (Ce6) at the N-terminus, a cysteine residue at the C-terminus, and a gelatinase cleavage site (PLGVRG) inserted between the C-terminal cysteine and the polycationic peptide. This multi-motif peptide assembles with gold nanoclusters (AuNc) via Au-thiol bonding and affords a gelatinase-responsive antibacterial photodynamic nanocomposite (GRAPN). In vitro results show that the gelatinase secreted by S. aureus can cleave and release APP from AuNc, thereby resulting in preferential killing of S. aureus over E. coli. In a mouse model of staphylococcal skin wound infection, by integrating gelatinase-responsive drug release and the synergistic effect of a photodynamic agent and APP, GRAPN exhibits a marked photodynamic antibacterial activity, effectively eradicates S. aureus infection, and promotes rapid healing of the infected wounds.
机译:金黄色葡萄球菌(金黄色葡萄球菌)相关的葡萄球菌感染是最常见的医院获得的感染类型之一,这需要在临床实践中进行选择性和有效的治疗方法。考虑到明胶酶作为S.UUREUS的特征,抗生素试剂的明胶酶响应释放,从而可以靶向致病性的金黄色葡萄球菌,同时在微生物中施加有益细菌。在这项工作中,我们通过在N-末端在C-末端的半胱氨酸残基(C-Terminus)下,通过在N-末端引入半胱氨酸残基,通过在N-末端引入杂种抗菌肽GKRWKWWRR来设计一种杂种抗菌光动力学肽(APP,CE6-GKRWWKWWRRGRGVRGVC),插入C-末端半胱氨酸和聚阳离子肽之间的明胶酶切割位点(PLGVRG)。该多基序肽通过Au-Thiol键合与金纳米蛋白(Aunc)组装,得到明胶酶响应性抗菌光动力纳米复合材料(GRAPN)。体外结果表明,由S.UUREUS分泌的明胶酶可以从Aunc中切割和释放APP,从而导致在大肠杆菌上杀死S.UUREUS。在葡萄球菌皮肤伤口感染的小鼠模型中,通过整合明胶酶反应药物释放和光动力剂和APP的协同作用,GRAPN表现出明显的光动力抗菌活性,有效地消除了金黄色葡萄球菌感染,并促进了感染的快速愈合伤口。

著录项

  • 来源
    《Biomaterials Science》 |2021年第9期|共12页
  • 作者单位

    Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology School of Pharmacy Changzhou University Changzhou Jiangsu 213164 China;

    Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology School of Pharmacy Changzhou University Changzhou Jiangsu 213164 China;

    Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology School of Pharmacy Changzhou University Changzhou Jiangsu 213164 China;

    Institute of Advanced Interdisciplinary Science School of Physics Shandong University Jinan 250100 China;

    Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology School of Pharmacy Changzhou University Changzhou Jiangsu 213164 China;

    Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology School of Pharmacy Changzhou University Changzhou Jiangsu 213164 China;

    Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology School of Pharmacy Changzhou University Changzhou Jiangsu 213164 China;

    Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology School of Pharmacy Changzhou University Changzhou Jiangsu 213164 China;

    Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology School of Pharmacy Changzhou University Changzhou Jiangsu 213164 China;

    Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology School of Pharmacy Changzhou University Changzhou Jiangsu 213164 China;

    Institute of Advanced Interdisciplinary Science School of Physics Shandong University Jinan 250100 China;

    Department of Chemistry the Chinese University of Hong Kong Shatin Hong Kong SAR China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 计量学;
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