MOE Key Laboratory of Advanced Textile Materials & Manufacturing Technology, Zhejiang Sci-Tech University, Hangzhou 310018, China.
Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, Zhejiang 310009, China; Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310009, China; Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, Zhejiang 310009, China.
J Control Release. 2020 May 10;321:463-474. doi: 10.1016/j.jconrel.2020.02.030. Epub 2020 Feb 19.
Sepsis is a complex disorder with very high morbidity and mortality; it can occur when an immune disorder triggers an invasion of pathogens in the host. Although many potential anti-infective and immunosuppressive treatments have been reported, we still do not have effective means of treating sepsis in clinic. The aim of this study is to develop a nanomaterial system that targets the site of inflammation and carries a combination of multiple drugs to better treat sepsis and alleviate its symptoms. We selected poly(lactide-co-glycolide acid) (PLGA) with good biocompatibility and degradability to prepare the nanoparticles (NPs) loaded with broad-spectrum antibiotic Sparfloxacin (SFX) and anti-inflammatory immunosuppressant Tacrolimus (TAC) by an emulsion-solvent evaporation method. The targeting ability of the NPs toward inflammatory sites is endowed by grafting of the γ3 peptide (NNQKIVNLKEKVAQLEA) that can specifically bind to the intercellular adhesion molecule-1 (ICAM-1), which is highly expressed on the surface of inflammatory endothelial cells. The drug loaded γ3-PLGA NPs have excellent cytocompatibility, low hemolysis ratio, and systemic toxicity. The drug loaded γ3-PLGA NPs also have excellent antibacterial property to both Gram-positive and Gram-negative bacteria and can effectively reduce the inflammation and immune response in acute lung infection mice. This study provides a simple and robust nanoplatform to treat lung infection induced sepsis, which may pave a way to design multifunctional nanomedicine for clinical translation.
脓毒症是一种复杂的疾病，发病率和死亡率都很高；当宿主的免疫紊乱引发病原体入侵时，就可能发生脓毒症。虽然已经报道了许多潜在的抗感染和免疫抑制治疗方法，但我们在临床上仍然没有有效的方法来治疗脓毒症。本研究的目的是开发一种针对炎症部位的纳米材料系统，该系统携带多种药物的组合，以更好地治疗脓毒症并减轻其症状。我们选择了具有良好生物相容性和可降解性的聚（乳酸-共-乙醇酸）（PLGA），通过乳液-溶剂蒸发法制备了载广谱抗生素司帕沙星（SFX）和抗炎免疫抑制剂他克莫司（TAC）的纳米颗粒（NPs）。NPs 对炎症部位的靶向能力是通过嫁接能够特异性结合细胞间黏附分子-1（ICAM-1）的 γ3 肽（NNQKIVNLKEKVAQLEA）而赋予的，ICAM-1 在炎症内皮细胞表面高度表达。载药 γ3-PLGA NPs 具有良好的细胞相容性、低溶血率和全身毒性。载药 γ3-PLGA NPs 对革兰氏阳性菌和革兰氏阴性菌均具有优异的抗菌性能，能有效减轻急性肺部感染小鼠的炎症和免疫反应。本研究提供了一种简单而强大的纳米平台来治疗肺部感染引起的脓毒症，这可能为设计用于临床转化的多功能纳米医学开辟了道路。
