Document Detail


Brain-targeting mechanisms of lactoferrin-modified DNA-loaded nanoparticles.
MedLine Citation:
PMID:  19654588     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ligand-mediated brain-targeting drug delivery is one of the focuses at present. Elucidation of exact targeting mechanisms serves to efficiently design these drug delivery systems. In our previous studies, lactoferrin (Lf) was successfully exploited as a brain-targeting ligand to modify cationic dendrimer-based nanoparticles (NPs). The mechanisms of Lf-modified NPs to the brain were systematically investigated in this study for the first time. The uptake of Lf-modified vectors and NPs by brain capillary endothelial cells (BCECs) was related to clathrin-dependent endocytosis, caveolae-mediated endocytosis, and macropinocytosis. The intracellular trafficking results showed that Lf-modified NPs could rapidly enter the acidic endolysosomal compartments within 5 mins and then partly escape within 30 mins. Both Lf-modified vectors and NPs showed higher blood-brain barrier-crossing efficiency than unmodified counterparts. All the results suggest that both receptor- and adsorptive-mediated mechanisms contribute to the cellular uptake of Lf-modified vectors and NPs. Enhanced brain-targeting delivery could be achieved through the synergistic effect of the macromolecular polymers and the ligand.
Authors:
Rongqin Huang; Weilun Ke; Liang Han; Yang Liu; Kun Shao; Liya Ye; Jinning Lou; Chen Jiang; Yuanying Pei
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-08-05
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  29     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-30     Completed Date:  2010-01-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1914-23     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / blood supply,  cytology,  metabolism*
Cell Membrane Permeability*
Cells, Cultured
Clathrin / metabolism
DNA / administration & dosage*
Drug Delivery Systems*
Endocytosis
Endothelial Cells / cytology,  metabolism
Gene Transfer Techniques
Lactoferrin / chemistry,  metabolism*
Male
Mice
Mice, Inbred BALB C
Microscopy, Confocal
Nanoparticles / chemistry*,  ultrastructure
Chemical
Reg. No./Substance:
0/Clathrin; 0/Lactoferrin; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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