Transferrin Functionization Elevates Transcytosis of Nanogranules across Epithelium by Triggering Polarity-Associated Transport Flow and Positive Cellular Feedback Loop
| Autor: | Xueqing Wang, Xing Tang, Qiang Zhang, Lan Yuan, Jian Zhang, Xiajuan Zou, Dan Yang, Hua Zhang, Bin Shao, Dechun Liu, Wenbing Dai, Bing He, Mengmeng Qin, Huiping Li, Hailiang Deng |
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| Rok vydání: | 2019 |
| Předmět: |
Male
General Physics and Astronomy 02 engineering and technology 010402 general chemistry Endocytosis 01 natural sciences Models Biological Exocytosis Epithelium Cell Line Dogs Downregulation and upregulation medicine Animals Humans Nanotechnology General Materials Science Secretion Rats Wistar chemistry.chemical_classification Feedback Physiological Chemistry General Engineering Transferrin Cell Polarity Biological Transport Serum Albumin Bovine 021001 nanoscience & nanotechnology 0104 chemical sciences Cell biology medicine.anatomical_structure Transcytosis Nanoparticles Cattle 0210 nano-technology Intracellular |
| Zdroj: | ACS nano. 13(5) |
| ISSN: | 1936-086X |
| Popis: | Overcoming the epithelial barriers to enhance drug transport is a focused topic for gastrointestinal, intratracheal, intranasal, vaginal, and intrauterine delivery. Nanomedicines with targeting functionization promote such a process owing to specific ligand-receptor interaction. However, compared to the cell uptake of targeting nanotherapies, currently few studies concentrate on their transcytosis including endocytosis for "in" and exocytosis for "out". In fact, the cellular regulatory mechanism for these pathways as well as the principle of ligand's effect on the transcytosis are almost ignored. Here, we fabricated transferrin (Tf) functionalized nanogranules (Tf-NG) as the nanomedicine model and confirmed the difference in polar distributions of Tf receptors (TfRs) between two epithelium models (bipolarity for Caco-2 and unipolarity for MDCK cells). Compared to the nonspecific reference, Tf-conjugation boosted the endocytosis by different pathways in two cell models and transformed the intracellular route of Tf-NG in both cells differently, affecting exocytosis, recycling, and degradation but not the secretion pathway. Only bipolar cells could establish a complete transport flow from "in" to "out", leading to the enhanced transcytosis of Tf-NG. Importantly, epithelia could make responses to Tf-NG transcytosis. Based on the quantitative proteomics, the intracellular trafficking of Tf-NG altered the protein expression profiles, in which the endocytosis- and transcytosis-related proteins were specifically upregulated. Particularly, only bipolar cells could positively feed back to such trafficking via accelerating the subsequent Tf-NG transcytosis. Here, all the cell transport of Tf-NG was polarity associated. In summary, Tf modification elevated the transcytosis of Tf-NG across the epithelium by triggering the polarity-associated transport flow and positive cell feedback loop. These findings provided an insight into the targeting nanodelivery for efficient transport through epithelial barriers. |
| Databáze: | OpenAIRE |
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