期刊
ACS APPLIED MATERIALS & INTERFACES
卷 10, 期 14, 页码 11443-11456出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.7b19153
关键词
mucin; nanoclustering corona; endocytosis; transcytosis; retrograde pathway
资金
- National Basic Research Program of China [2015CB932100]
- National Natural Science Foundation of China [81690264]
- Innovation Team of the Ministry of Education [BMU20110263]
Mucus, which is secreted by the goblet cells of enterocytes, constitutes the first obstacle encountered for the intestinal absorption of nanomedicines. For decades, mucus has simply been regarded as a physical barrier that hinders the permeation and absorption of drugs, because of its high viscosity and reticular structure, whereas the interaction of mucus ingredients with nanomedicines is usually neglected. It is unclear whether glycoproteins, as the main components of mucus, interact with nanomedicines. We also do not know how the potential interaction affects the subsequent transportation of nanomedicines through the intestinal epithelium. In this study, mucin as the key element of mucus was investigated to characterize the interaction of nanomedicines with mucus. PEG-modified gold nanoparticles (PGNPs) were fabricated as model nanoparticles. Mucin was found to adhere to the nanoparticle surface to form a corona structure and induce the clustering of PGNPs by joining particles together, demonstrating the interaction between mucin and PGNPs. In addition, two intestinal epithelia, Caco-2 (non-mucus secretion) and HT-29 (high mucus secretion), were compared to evaluate the influence of mucin on the cellular interaction of PGNPs. Amazingly, mucin altered the trafficking characteristic of PGNPs in intestinal epithelium. Both in vitro and in vivo investigations demonstrated more nanoparticles being internalized by cells due to the mucin coverage. However, mucin induced a significant reduction in the transcytosis of PGNPs across epithelial monolayers. The mechanism exploration further revealed that the more endocytosis but less transcytosis (MELT) effect was mainly attributed to the strengthened retrograde pathway in which more PGNPs were transported to Golgi apparatus and exocytosed back to the apical but not the basolateral side of the epithelial monolayers. The MELT effect endowed mucin with duality in the nanoparticle transportation. Therefore, the rational regulation based on the MELT effect will provide new insight into overcoming the mucus obstacle as a barrier and enhancing the oral absorption rate of nanomedicines.
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