Bioresponsive Nanoparticles Targeted to Infectious Microenvironments for Sepsis Management.
Bioresponsive Nanoparticles Targeted to Infectious Microenvironments for Sepsis Management.
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DOI：
10.1002/adma.201803618
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发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Zhang CY;Gao J;Wang Z
脓毒症是由宿主对细菌感染的免疫反应失调引起的危及生命的疾病，在世界范围内持续引起高发病率和死亡率。尽管发现了许多潜在的治疗靶点，但缺乏有效的脓毒症治疗方法。在这里，报告了一种通过生物响应纳米颗粒靶向感染性微环境（IME）的策略，该纳米颗粒同时消除细菌并减轻宿主炎症反应，从而管理小鼠的败血症。纳米颗粒由对pH和细菌酶敏感的共聚物制成，以自组装成装载有抗生素（环丙沙星）和抗炎剂（（2-[（氨基羰基）氨基]-5-（4-氟苯基）-3-噻吩甲酰胺）的胶束。此外，纳米颗粒与靶向IME的细胞间粘附分子-1抗体缀合。使用急性肺细菌感染小鼠模型证明了靶向IME和局部线索作为触发剂以按需方式递送治疗剂的纳米颗粒。在由腹膜炎以致死剂量的细菌入侵诱导的脓毒症小鼠模型中，显示同时靶向病原体和过度炎症途径对于管理脓毒症是有价值的。该研究不仅说明了一种新的递送系统的发展，而且还说明了纳米医学对感染性疾病的基于机制的治疗。
Sepsis is a life-threatening disease resulted from a dysregulated host immune response to bacterial infections, continuing to cause high morbidity and mortality worldwide. Despite discoveries of many potential therapeutic targets, effective treatments of sepsis are lacking. Here, a strategy is reported to target infectious microenvironments (IMEs) via bioresponsive nanoparticles that simultaneously eliminate bacteria and alleviate the host inflammation response, thus managing sepsis in mice. The nanoparticle is made of copolymers sensitive to pH and bacterial enzymes to self-assemble into a micelle loaded with both an antibiotic (ciprofloxacin) and an anti-inflammatory agent ((2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide). In addition, the nanoparticle is conjugated with intercellular adhesion molecule-1 antibodies to target IMEs. Nanoparticle targeting to IMEs and local cues as triggers to deliver therapeutics in on-demand manners is demonstrated using an acute lung bacterial infection mouse model. In the sepsis mouse model induced by peritonitis at a lethal dose of bacterial invasion, it is shown that concurrently targeting pathogens and excessive inflammation pathways is valuable to manage the sepsis. The study illustrates not only the development of a new delivery system but also the mechanism-based therapy of nanomedicine for infectious diseases.
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