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.
Biomater Sci. 2021 May 4;9(9):3433-3444. doi: 10.1039/d0bm02201b.
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.
金黄色葡萄球菌（S. aureus）相关的葡萄球菌感染是最常见的医院获得性感染类型之一，在临床实践中需要进行有针对性和有效的治疗。鉴于明胶酶是金黄色葡萄球菌的特征之一，因此明胶酶响应型释放抗生素试剂可以靶向致病性金黄色葡萄球菌，同时保护微生物群落中的有益细菌。在这项工作中，我们设计了一种基于聚阳离子抗菌肽 GKRWWKWWRR 的杂化抗菌光动力肽（APP，Ce6-GKRWWKWWRRPLGVRGC），通过在 N 端引入光敏剂氯仿 e6（Ce6）、C 端的半胱氨酸残基和 C 端半胱氨酸和聚阳离子肽之间插入的明胶酶切割位点（PLGVRG）。这种多基序肽通过 Au-巯基键与金纳米簇（AuNc）组装，并提供一种明胶酶响应性抗菌光动力纳米复合材料（GRAPN）。体外结果表明，金黄色葡萄球菌分泌的明胶酶可以切割并从 AuNc 上释放 APP，从而导致对金黄色葡萄球菌的选择性杀伤，而对大肠杆菌没有杀伤作用。在金黄色葡萄球菌皮肤伤口感染的小鼠模型中，通过整合明胶酶响应性药物释放以及光动力剂和 APP 的协同作用，GRAPN 表现出显著的光动力抗菌活性，有效根除金黄色葡萄球菌感染，并促进受感染伤口的快速愈合。
