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Bioresponsive Nanoparticles Targeted to Infectious Microenvironments for Sepsis Management
Advanced Materials ( IF 27.4 ) Pub Date : 2018-09-11 , DOI: 10.1002/adma.201803618 Can Yang Zhang 1 , Jin Gao 1 , Zhenjia Wang 1
Advanced Materials ( IF 27.4 ) Pub Date : 2018-09-11 , DOI: 10.1002/adma.201803618 Can Yang Zhang 1 , Jin Gao 1 , Zhenjia Wang 1
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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.
中文翻译：
针对感染性微环境的生物响应纳米颗粒用于脓毒症管理
脓毒症是一种危及生命的疾病，是由宿主对细菌感染的免疫反应失调引起的，在全世界范围内持续导致高发病率和死亡率。尽管发现了许多潜在的治疗靶点，但仍缺乏脓毒症的有效治疗方法。据报道，一种策略是通过生物响应纳米颗粒瞄准感染性微环境（IME），同时消除细菌并减轻宿主炎症反应，从而控制小鼠的败血症。该纳米颗粒由对 pH 值和细菌酶敏感的共聚物制成，可自组装成载有抗生素（环丙沙星）和抗炎剂（（2-[（氨基羰基）氨基]-5-（4-氟苯基）的胶束） )-3-噻吩甲酰胺）此外，纳米颗粒与细胞间粘附分子-1 抗体结合，以靶向 IME 和局部线索作为触发因素，通过急性肺部细菌感染来提供治疗。在由致死剂量的细菌侵入引起的腹膜炎小鼠模型中，研究表明同时针对病原体和过度炎症途径对于控制脓毒症很有价值。还有基于机制的纳米医学治疗传染病。
更新日期：2018-09-11
中文翻译：
针对感染性微环境的生物响应纳米颗粒用于脓毒症管理
脓毒症是一种危及生命的疾病，是由宿主对细菌感染的免疫反应失调引起的，在全世界范围内持续导致高发病率和死亡率。尽管发现了许多潜在的治疗靶点，但仍缺乏脓毒症的有效治疗方法。据报道，一种策略是通过生物响应纳米颗粒瞄准感染性微环境（IME），同时消除细菌并减轻宿主炎症反应，从而控制小鼠的败血症。该纳米颗粒由对 pH 值和细菌酶敏感的共聚物制成，可自组装成载有抗生素（环丙沙星）和抗炎剂（（2-[（氨基羰基）氨基]-5-（4-氟苯基）的胶束） )-3-噻吩甲酰胺）此外，纳米颗粒与细胞间粘附分子-1 抗体结合，以靶向 IME 和局部线索作为触发因素，通过急性肺部细菌感染来提供治疗。在由致死剂量的细菌侵入引起的腹膜炎小鼠模型中，研究表明同时针对病原体和过度炎症途径对于控制脓毒症很有价值。还有基于机制的纳米医学治疗传染病。
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