A multitude of serious chronic infections are involved in bacterial biofilms that are difficult to eradicate. Here, a water-soluble galactose-functionalized cationic 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based photodynamic therapy agent was synthesized for selectively eliminating the bacterial biofilm. These conjugates can capture bacteria to form aggregations through electrostatic interaction and then generate a large number of reactive oxygen species (ROS) under visible light irradiation to kill the bacteria without the emergence of bacterial resistance. Simultaneously, this agent could effectively inhibit and eradicate both Gram-positive and Gram-negative bacterial biofilms. The in-depth analysis of the antimicrobial mechanism confirmed that the conjugates can quickly bind on the bacterial surface, irreversibly disrupt the bacterial membrane, and distinctly inhibit intracellular enzyme activity, ultimately leading to the bacterial death. Importantly, these conjugates are highly selective toward bacterial cells over mammalian cells as well as no cytotoxicity to A549 cells and no discernible hemolytic activity. Collectively, this water-soluble galactose-decorated cationic BODIPY-based photodynamic therapy agent design provides promising insights for the development of therapy for antibiotic-resistant bacteria.

中文翻译：

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基于BODIPY的水溶性半乳糖修饰阳离子光动力治疗剂选择性消除生物膜

难以根除的细菌生物膜涉及多种严重的慢性感染。在此，合成了水溶性半乳糖官能化的阳离子4,4-二氟-4-硼-3a，4a-二氮杂-s-茚满二烯（BODIPY）基光动力治疗剂，用于选择性消除细菌生物膜。这些结合物可以通过静电相互作用捕获细菌以形成聚集体，然后在可见光照射下产生大量活性氧（ROS），以杀死细菌而不会出现细菌抗性。同时，该试剂可有效抑制和根除革兰氏阳性和革兰氏阴性细菌生物膜。对抗菌机制的深入分析证实，结合物可以快速结合在细菌表面，不可逆转地破坏细菌膜，并明显抑制细胞内酶活性，最终导致细菌死亡。重要的是，这些缀合物对细菌细胞具有比哺乳动物细胞高的选择性，并且对A549细胞没有细胞毒性，也没有明显的溶血活性。总的来说，这种基于水溶性半乳糖修饰的阳离子BODIPY的光动力疗法剂的设计为开发抗药性细菌的疗法提供了有希望的见识。