Hou Xiaoxue, Yang Lijun, Liu Jinjian, Zhang Yumin, Chu Liping, Ren Chunyan, Huang Fan, Liu Jianfeng
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, P. R. China.
Biomater Sci. 2020 Nov 21;8(22):6350-6361. doi: 10.1039/d0bm01084g. Epub 2020 Oct 7.
Drug-resistant bacterial infections have stolen the spotlight in recent years as stubborn diseases intimidating public health, thus urgently requiring the development of innovative treatment strategies with high antibacterial efficiency and low bacterial resistance. Here, a polymeric antimicrobial with synergistic chemo-photodynamic therapy function is fabricated to combat drug-resistant bacterial infections. In this strategy, polymeric micelles based on amphiphilic poly(aspartic acid)-block-poly(ε-caprolactone) (PAsp-b-PCL) are used as nanocarriers to encapsulate a photosensitizer protoporphyrin IX (PpIX) in the micellar core, which then undergo silver nanoparticle decoration on the micellar shell through an in situ reduction method. Compared with mono-therapy, the combination of silver nanoparticle decoration and light-activatable PpIX enables the resulting polymeric antimicrobial to exert chemo-photodynamic activity to kill drug-resistant bacteria more potently in vitro. Furthermore, the prepared polymeric antimicrobials with synergistic antibacterial activity show robust eradication efficacy against subcutaneous infections induced by drug-resistant Staphylococcus aureus in a murine model. Therefore, our study provides a simple and potent strategy to realize combination therapy for eradicating drug-resistant bacterial infections.
近年来，耐药细菌感染已成为威胁公众健康的顽固疾病，备受关注，因此迫切需要开发具有高抗菌效率和低细菌耐药性的创新治疗策略。在此，制备了一种具有协同化学-光动力疗法功能的聚合物抗菌剂，以对抗耐药细菌感染。在该策略中，基于两亲性聚（天冬氨酸）-嵌段-聚（ε-己内酯）（PAsp-b-PCL）的聚合物胶束用作纳米载体，将光敏剂原卟啉IX（PpIX）包裹在胶束核心中，然后通过原位还原法在胶束外壳上进行银纳米颗粒修饰。与单一疗法相比，银纳米颗粒修饰和可光激活的PpIX相结合，使所得聚合物抗菌剂在体外更有效地发挥化学-光动力活性以杀死耐药细菌。此外，所制备的具有协同抗菌活性的聚合物抗菌剂在小鼠模型中对耐药金黄色葡萄球菌引起的皮下感染显示出强大的根除效果。因此，我们的研究提供了一种简单有效的策略来实现联合治疗以根除耐药细菌感染。
