Data_Sheet_1_Hydrogen sulfide-sensitive Chitosan-SS-Levofloxacin micelles with a high drug content: Facile synthesis and targeted Salmonella infection therapy.docx

The delivery system of antibiotics plays an important role in increasing the drug efficacy and reducing the risks of off-target toxicities and antibiotic resistance. The pathophysiology of bacterial infections is similar to that of tumor tissues, but only a few delivery systems have been able to target and release antibiotics on demand. Herein, we designed and developed a robust Chitosan-SS-Levofloxacin (CS-SS-LF) micelles for targeted antibiotic delivery, in which disulfide bond can be reduced by hydrogen sulfide (H2S), a typical product of Salmonella, and subsequently released antibiotic to eradicate Salmonella infection. CS-SS-LF micelles showed uniform size and sharp response to H2S. Compared with levofloxacin alone, these micelles possessed a better capacity in disrupting Salmonella biofilms and reducing bacterial burden in organs. The H2S-sensitive CS-SS-LF micelles might enable a new way to address bacterial infections.

抗生素递送系统对于提升药物疗效、降低脱靶毒性与抗生素耐药性风险具有重要意义。细菌性感染的病理生理过程与肿瘤组织相似，但目前仅有极少数递送系统能够实现靶向递送并按需释放抗生素。为此，我们设计并开发了一种性能稳定的壳聚糖-二硫键-左氧氟沙星(Chitosan-SS-Levofloxacin, CS-SS-LF)胶束用于靶向抗生素递送：该载体中的二硫键(disulfide bond)可被沙门氏菌(Salmonella)的典型代谢产物硫化氢(H2S)还原，进而释放抗生素以根除沙门氏菌感染。CS-SS-LF胶束粒径均一，且对硫化氢具有灵敏的响应性。与单独使用左氧氟沙星相比，该胶束在破坏沙门氏菌生物被膜、降低器官内细菌载量方面表现更优。这种对硫化氢敏感的CS-SS-LF胶束或许能为细菌性感染的治疗提供全新策略。