Self-Assembled Rose Bengal-Exopolysaccharide Nanoparticles for Improved Photodynamic Inactivation of Bacteria by Enhancing Singlet Oxygen Generation Directly in the Solution
Self-Assembled Rose Bengal-Exopolysaccharide Nanoparticles for Improved Photodynamic Inactivation of Bacteria by Enhancing Singlet Oxygen Generation Directly in the Solution
复制标题
自组装玫瑰红-胞外多糖纳米颗粒通过直接增强溶液中的单线态氧气生成来改善细菌的光动力灭活
DOI：
10.1021/acsami.8b01545
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发表时间：
2018-05-16
影响因子：
9.5
通讯作者：
Chen, Zhan
中科院分区：
文献类型：
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作者：
Li, Chengcheng;Lin, Fengming;Chen, Zhan
开发新的抗菌光动力疗法（PDT）策略以提高非阳离子光敏剂的抗菌PDT功效而不引入细胞毒性具有重要价值，这是当前基于细胞表面工程的抗菌PDT的主要努力的巨大挑战。在这项研究中，疏水性和阴离子光敏剂玫瑰红（RB）与细菌胞外多糖（EPS）化学缀合，生成两亲性和带负电荷的化合物EPS-RB，该化合物可以在溶液中自组装成纳米颗粒（NPs）。这些EPS-RB NP在溶液中具有增加的单线态氧产生性质。结果，EPS-RB对革兰氏阴性和革兰氏阳性细菌都表现出改善的光灭活作用，导致RB工作浓度达到创纪录的低水平，分别为8 μ M或500 nM（对于大肠杆菌或金黄色葡萄球菌）。光照射后，EPS-RB比RB更多地结合到细胞表面并渗透到细菌中，EPS-RB停留在照射最多的E.大肠杆菌，而进入所有照射的S.金黄色。扫描电镜和荧光共聚焦成像结果均表明，E.大肠杆菌被严重破坏，而S.金黄色。所有这些观察结果表明，EPS-RB NP在溶液中的增强的单线态氧产生及其因此增加的膜结合和通过受损细胞膜进入细菌的细胞渗透有助于其显著改善的细菌光灭活效率。此外，EPS-RB具有低细胞毒性和可忽略的溶血活性，显示出良好的生物相容性。因此，EPS-RB的构建为分离的细胞/敏化剂系统的PDT有效性改进以及因此下一代抗菌剂的设计提供了新的策略。
It is of great value to develop new antibacterial photodynamic therapy (PDT) strategies to improve antibacterial PDT efficacy of noncationic photosensitizers without introducing cytotoxicity, which is a great challenge for current leading efforts on antimicrobial PDT based on cell surface engineering. In this research, the hydrophobic and anionic photosensitizer rose bengal (RB) was chemically conjugated with bacterial exopolysaccharide (EPS) to generate an amphiphilic and negatively charged compound EPS-RB that could self-assemble into nanoparticles (NPs) in solution. These EPS-RB NPs possessed an increased singlet oxygen generation property in solution. As a result, EPS-RB exhibited improved photoinactivation for both Gram-negative and Gram-positive bacteria, leading to a record low RB working concentration, 8 mu M or 500 nM for Escherichia coli or Staphylococcus aureus, respectively. Upon light irradiation, more EPS-RB bound to the cell surface and penetrated into bacteria than RB, with EPS-RB staying around the cell surface of the most irradiated E. coli while entering all irradiated S. aureus. Both scanning electron microscopy and fluorescence confocal imaging results show that the cell membrane of E. coli was damaged heavily but not S. aureus. All of these observations indicate that both the enhanced singlet oxygen production of EPS-RB NPs in solution and their consequently increased membrane binding and cellular penetration into the bacteria through the damaged cell membrane contribute to their significantly improved bacterial photoinactivation efficiency. In addition, EPS-RB has low cytotoxicity and negligible hemolytic activity, showing great biocompatibility. Therefore, the construction of EPS-RB provides a new strategy for the PDT effectiveness improvement of the separated cell/sensitizer systems and thus the design of next-generation antimicrobial agents.