Document Detail


Protein-nanoparticle conjugates as potential therapeutic agents for the treatment of hyperlipidemia.
MedLine Citation:
PMID:  20534889     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hyperlipidemia, a condition associated with atherosclerosis, can develop because of the lack of low density lipoprotein (LDL) receptors in hepatocytes. Since injected polymeric nanoparticles are quickly taken up by the liver Kupffer cells, we hypothesize that it is possible to enhance LDL delivery to the liver through the use of LDL-absorbing nanoparticles. Here, we demonstrate the feasibility of the proposed approach in vitro. We used biodegradable and biocompatible polylactide nanoparticles (approximately 100 nm in diameter) with covalently attached apolipoprotein B100 antibody to adsorb LDLs at physiologically relevant concentrations. We showed that up to sixfold decreases of LDL levels can be achieved in vitro upon treatment of LDL suspensions (500 mg dl( - 1)) with anti-apoB100-nanoparticle conjugates. The study of the uptake of the antibody-nanoparticle-LDL complexes by cells was performed using a mouse macrophage cell line (RAW 264.7) as a model for liver Kupffer cells. We found that macrophages can quickly take up antibody-nanoparticle-LDL complexes and digest them within 24 h. No evidence of cytotoxicity was observed for the experimental conditions used in this study.
Authors:
V D Maximov; V V Reukov; J N Barry; C Cochrane; A A Vertegel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-10
Journal Detail:
Title:  Nanotechnology     Volume:  21     ISSN:  1361-6528     ISO Abbreviation:  Nanotechnology     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-22     Completed Date:  2010-10-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101241272     Medline TA:  Nanotechnology     Country:  England    
Other Details:
Languages:  eng     Pagination:  265103     Citation Subset:  IM    
Affiliation:
Department of Bioengineering, Clemson University, Clemson, SC 29631, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies / therapeutic use*
Apolipoprotein B-100 / immunology
Cell Death / drug effects
Cell Survival / drug effects
Cells, Cultured
Humans
Hyperlipidemias / therapy*
Light
Lipoproteins, LDL / therapeutic use*
Macrophages / cytology,  drug effects,  metabolism,  ultrastructure
Mice
Microscopy, Atomic Force
Microscopy, Confocal
Microscopy, Fluorescence
Nanoparticles / therapeutic use*,  ultrastructure
Particle Size
Polyesters / pharmacology
Scattering, Radiation
Time Factors
Titrimetry
Chemical
Reg. No./Substance:
0/Antibodies; 0/Apolipoprotein B-100; 0/Lipoproteins, LDL; 0/Polyesters; 26969-66-4/poly(lactide)

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