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Zebrafish: A Visual Model to Evaluate the Biofate of Transferrin Receptor-Targeted 7Peptide-Decorated Coumarin 6 Micelles
Ye Li3; Xiaoning Song2; Xiang Yi1; Ruibing Wang3; Simon Ming-Yuen Lee3; Xueqing Wang2; Ying Zheng3
2017-11-08
Source PublicationACS Applied Materials and Interfaces
ISSN19448252 19448244
Volume9Issue:44Pages:39048-39058
Abstract

In the present study, the zebrafish was explored as an in vivo model to assess the biofate of transferrin receptor (TfR)-targeted coumarin 6 (C6) micelles across various biological barriers. Three 7peptide (7pep)-decorated poly(ethylene glycol)-block-poly(ϵ-caprolactone) micelles loaded with fluorescence coumarin 6 (7pep-M-C6) with different ligand densities were constructed with particle sizes between 30 and 40 nm. Whole-mount immunostaining revealed that the expression level of TfR in the retina, brain, and intestine increased along with development stage. Compared to unmodified micelles, 7pep-M-C6 demonstrated higher uptake efficiency in the larval zebrafish. Preinhibition of TfR with 7pep implicated the TfR-mediated endocytosis pathway in the uptake of 7pep-M-C6. Confocal images of the larval zebrafish eye and brain showed the efficient delivery of C6 across the retinal pigment epithelial to the ganglion cell layer and the significant accumulation of C6 in all brain tissues, respectively, which plateaued when the ligand density was 10%. To investigate the intestinal distribution of C6, micelles were administered to adult zebrafish via gavaging. Notably, 7pep-M-C6 enhanced the transport of C6 across the villi and increased its aggregation into the basolateral membrane of the intestine. After the oral administration of 7pep-M-C6, C6 accumulated in the eye and brain. Förster resonance energy transfer analysis suggested that intact 7pep-modified micelles could enter the epithelial cells of the intestine, brain, and eye after oral administration in adult zebrafish. In conclusion, zebrafish could be used as a model for in vivo visual assessment of the biofate of TfR-targeted drug delivery systems.

Keyword7peptide Biological Barriers Ligand Density Poly(Ethylene Glycol)-block-Poly(Ε-caprolactone) Micelles Transferrin Receptor Zebrafish
DOI10.1021/acsami.7b12809
URLView the original
Indexed BySCIE
WOS Research AreaScience & Technology - Other Topics ; Materials Science
WOS SubjectNanoscience & Nanotechnology ; Materials Science, Multidisciplinary
WOS IDWOS:000415140800096
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Cited Times [WOS]:12   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorXueqing Wang; Ying Zheng
Affiliation1.Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
2.Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
3.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Ye Li,Xiaoning Song,Xiang Yi,et al. Zebrafish: A Visual Model to Evaluate the Biofate of Transferrin Receptor-Targeted 7Peptide-Decorated Coumarin 6 Micelles[J]. ACS Applied Materials and Interfaces,2017,9(44):39048-39058.
APA Ye Li,Xiaoning Song,Xiang Yi,Ruibing Wang,Simon Ming-Yuen Lee,Xueqing Wang,&Ying Zheng.(2017).Zebrafish: A Visual Model to Evaluate the Biofate of Transferrin Receptor-Targeted 7Peptide-Decorated Coumarin 6 Micelles.ACS Applied Materials and Interfaces,9(44),39048-39058.
MLA Ye Li,et al."Zebrafish: A Visual Model to Evaluate the Biofate of Transferrin Receptor-Targeted 7Peptide-Decorated Coumarin 6 Micelles".ACS Applied Materials and Interfaces 9.44(2017):39048-39058.
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