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Nanoparticles Targeted against Cryptococcal Pneumonia by Interactions between Chitosan and Its Peptide Ligand
Nano Letters ( IF 9.6 ) Pub Date : 2018-09-27 00:00:00 , DOI: 10.1021/acs.nanolett.8b02229 Yixuan Tang 1 , Shuang Wu 1 , Jiaqi Lin 2 , Liting Cheng 1 , Jing Zhou 1 , Jing Xie 1 , Kexin Huang 1 , Xiaoyou Wang 1 , Yang Yu 1 , Zhangbao Chen 1 , Guojian Liao 1 , Chong Li 1
Nano Letters ( IF 9.6 ) Pub Date : 2018-09-27 00:00:00 , DOI: 10.1021/acs.nanolett.8b02229 Yixuan Tang 1 , Shuang Wu 1 , Jiaqi Lin 2 , Liting Cheng 1 , Jing Zhou 1 , Jing Xie 1 , Kexin Huang 1 , Xiaoyou Wang 1 , Yang Yu 1 , Zhangbao Chen 1 , Guojian Liao 1 , Chong Li 1
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Inspired by the fact that chitosan is a representative constituent of the ectocellular structure of Cryptococcus neoformans and a typical biomaterial for improving drug oral absorption, we designed an elegant and efficient C. neoformans-targeted drug delivery system via oral administration. A chitosan-binding peptide screened by phage display was used as the targeting moiety, followed by conjugation to the surface of poly(lactic-co-glycolic acid) nanoparticles as the drug carrier, which was then incubated with free chitosan. The noncovalently bound chitosan adheres to mucus layers and significantly enhances penetration of nanoparticles through the oral absorption barrier into circulation and then re-exposed the targeting ligand for later recognition of the fungal pathogen at the site of infection. After loading itraconazole as a model drug, our drug delivery system remarkably cleared lung infections of C. neoformans and increased survival of model mice. Currently, targeted drug delivery is mainly performed intravenously; however, the system described in our study may provide a universal means to facilitate drug targeting to specific tissues and disease sites by oral administration and may be especially powerful in the fight against increasingly severe fungal infections.
中文翻译：
壳聚糖及其肽配体之间的相互作用靶向针对隐球菌性肺炎的纳米颗粒。
的事实，脱乙酰壳多糖是的ectocellular结构的代表性的构成启发新型隐球菌和用于改善药物的口服吸收的典型的生物材料，我们设计一个优雅和高效的新生隐球菌通过口服给药靶向性药物递送系统。通过噬菌体展示筛选壳聚糖结合肽被用作靶向部分，随后通过缀合至聚的表面（乳酸-共-乙醇酸）纳米颗粒作为药物载体，然后与游离的壳聚糖一起孵育。非共价结合的壳聚糖粘附在粘液层上，并显着增强纳米颗粒通过口服吸收屏障进入循环系统的渗透，然后重新暴露靶向配体，以便以后在感染部位识别真菌病原体。在将伊曲康唑用作模型药物后，我们的给药系统显着清除了新孢梭菌的肺部感染并提高了模型小鼠的存活率。目前，靶向药物递送主要是静脉内进行的。然而，我们的研究中描述的系统可能提供了一种通用的方法，可以通过口服给药促进药物靶向特定组织和疾病部位，并且在对抗日益严重的真菌感染方面可能特别强大。
更新日期：2018-09-27
中文翻译：
壳聚糖及其肽配体之间的相互作用靶向针对隐球菌性肺炎的纳米颗粒。
的事实，脱乙酰壳多糖是的ectocellular结构的代表性的构成启发新型隐球菌和用于改善药物的口服吸收的典型的生物材料，我们设计一个优雅和高效的新生隐球菌通过口服给药靶向性药物递送系统。通过噬菌体展示筛选壳聚糖结合肽被用作靶向部分，随后通过缀合至聚的表面（乳酸-共-乙醇酸）纳米颗粒作为药物载体，然后与游离的壳聚糖一起孵育。非共价结合的壳聚糖粘附在粘液层上，并显着增强纳米颗粒通过口服吸收屏障进入循环系统的渗透，然后重新暴露靶向配体，以便以后在感染部位识别真菌病原体。在将伊曲康唑用作模型药物后，我们的给药系统显着清除了新孢梭菌的肺部感染并提高了模型小鼠的存活率。目前，靶向药物递送主要是静脉内进行的。然而，我们的研究中描述的系统可能提供了一种通用的方法，可以通过口服给药促进药物靶向特定组织和疾病部位，并且在对抗日益严重的真菌感染方面可能特别强大。
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