Nanoparticles Targeted against Cryptococcal Pneumonia by Interactions between Chitosan and Its Peptide Ligand
Nanoparticles Targeted against Cryptococcal Pneumonia by Interactions between Chitosan and Its Peptide Ligand
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通过壳聚糖与其肽配体之间的相互作用靶向治疗隐球菌肺炎的纳米颗粒
DOI：
10.1021/acs.nanolett.8b02229
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发表时间：
2018
期刊：
影响因子：
10.8
通讯作者：
Li Chong
中科院分区：
文献类型：
--
作者：
Tang Yixuan;Wu Shuang;Lin Jiaqi;Cheng Liting;Zhou Jing;Xie Jing;Huang Kexin;Wang Xiaoyou;Yu Yang;Chen Zhangbao;Liao Guojian;Li Chong
壳聚糖是新型隐球菌胞外结构的代表成分，是促进药物口服吸收的典型生物材料。通过口服给药的肿瘤靶向给药系统。利用噬菌体展示筛选的壳聚糖结合肽作为靶向片段，偶联到聚乳酸-羟基乙酸纳米颗粒表面作为药物载体，与游离壳聚糖孵育。非共价结合的壳聚糖粘附在黏液层上，显著增强纳米颗粒通过口腔吸收屏障进入循环，然后重新暴露靶向配体，以便稍后在感染部位识别真菌病原体。在以伊曲康唑为模型药物后，我们的给药系统显著清除了肺部感染。新基因和提高模型小鼠存活率。目前，靶向给药主要是静脉注射；然而，我们研究中描述的系统可能提供一种通用的方法，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有效。
Inspired by the fact that chitosan is a representative constituent of the ectocellular structure ofCryptococcus neoformansand a typical biomaterial for improving drug oral absorption, we designed an elegant and efficientC. 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 ofC. neoformansand 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.