Document Detail

Synthesis and grafting of thioctic acid-PEG-folate conjugates onto Au nanoparticles for selective targeting of folate receptor-positive tumor cells.
MedLine Citation:
PMID:  16704197     Owner:  NLM     Status:  MEDLINE    
This paper reports the creation of Au nanoparticles (AuNP) that are soluble in aqueous solution over a broad range of pH and ionic strength values and that are capable of selective uptake by folate receptor positive (FR+) cancer cells. A novel poly(ethylene glycol) (PEG) construct with thioctic acid and folic acid coupled on opposite ends of the polymer chain was synthesized for targeting the AuNP to FR+ tumor cells via receptor-mediated endocytosis. These folic acid-PEG-thioctic acid conjugates were grafted onto 10-nm-diameter Au particles in aqueous solution. The resulting folate-PEG-coated nanoparticles do not aggregate over a pH range of from 2 to 12 and at electrolyte concentrations of up to 0.5 M NaCl with particle concentrations as high as 1.5 x 10(13) particles/mL. Transmission electron microscopy was used to document the performance of these coated nanoparticles in cell culture. Selective uptake of folate-PEG grafted AuNPs by KB cells, a FR+ cell line that overexpress the folate receptor, was observed. AuNP uptake was minimal in cells that (1) do not overexpress the folate receptor, (2) were exposed to AuNP lacking the folate-PEG conjugate, or (3) were co-incubated with free folic acid in large excess relative to the folate-PEG grafted AuNP. Understanding this process is an important step in the development of methods that use targeted metal nanoparticles for tumor imaging and ablation.
Vivechana Dixit; Jeroen Van den Bossche; Debra M Sherman; David H Thompson; Ronald P Andres
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  17     ISSN:  1043-1802     ISO Abbreviation:  Bioconjug. Chem.     Publication Date:    2006 May-Jun
Date Detail:
Created Date:  2006-05-17     Completed Date:  2006-07-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  603-9     Citation Subset:  IM    
School of Chemical Engineering, Department of Chemistry, Life Science Microscopy Facility, Purdue University, West Lafayette, Indiana 47907, USA.
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MeSH Terms
Carrier Proteins / metabolism*
Cell Line, Tumor
Folic Acid / chemical synthesis,  chemistry*,  metabolism*
Gold / chemistry*
Microscopy, Electron, Transmission
Molecular Structure
Nanostructures / chemistry*,  ultrastructure
Neoplasms / metabolism*,  ultrastructure
Polyethylene Glycols / chemistry
Receptors, Cell Surface / metabolism*
Thioctic Acid / chemistry*
Reg. No./Substance:
0/Carrier Proteins; 0/Polyethylene Glycols; 0/Receptors, Cell Surface; 0/folate-binding protein; 59-30-3/Folic Acid; 62-46-4/Thioctic Acid; 7440-57-5/Gold

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