Article

Fabrication and functional characterization of goldnanoconjugates for potential application in ovarian cancer.

Department of Biochemistry and Molecular Biology, 200 First Street SW, Mayo Clinic, Rochester, MN 55905.
Journal of Materials Chemistry (impact factor: 5.97). 01/2010; 20(3):547-554. DOI:10.1039/b913224d pp.547-554
Source: PubMed

ABSTRACT In this paper we report the surface modification and functional characterization of a gold nanoparticle-based drug delivery system for potential therapeutic application in ovarian cancer. It is currently recognized that nanotechnology may play a pivotal role in drug delivery by increasing efficacy and reducing toxicity of anti-cancer drugs. Here, we report the fabrication of a gold nanoparticles (AuNP) based drug delivery system consisting of folic acid (FA), mercapto-polyethylene glycol (PEG-SH) with a molecular weight of 2000 (designated as PSH2-2K or PSH) and cis-platin (CP) [Au-PSH-CP-FA] for potential therapeutic application in ovarian cancer. Fabrication is done in a three steps incubation process at room temperature (RT). The gold nanoconjugates are characterized with several physico-chemical techniques such as UV-Vis (UV-Visible spectroscopy), TEM (Transmission electron microscopy), ICP (Inductively coupled plasma) and radioactivity measurement with a scintillation counter. Attachment and release profiles of FA from the gold nanoconjugates are performed using (3)H-labelled FA ((3)H-FA). The expressions of folate receptor (FR) for ovarian cancer cell lines (OV-167, OVCAR-5), human umbilical vein endothelial cells (HUVEC) and ovarian surface epithelial (OSE) cells are determined by FACS analysis. Quantitation of platinum content in the nanoconjugates and its release profile is determined by platinum (Pt) analysis using ICP-MS. Biological functional characterization using in vitro proliferation assay demonstrates that Au-PSH-CP-FA not only retains the cytotoxic effect of CP, but it protects the normal cells from the cytotoxic insult, while enhancing the cytotoxic effect on the tumor cells. In future, this strategy may be utilized as a strategy for the treatment of ovarian cancers and may overcome the core side effect issues in anticancer therapy.

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    Article: Cytotoxicity of naphthoquinones and their capacity to generate reactive oxygen species is quenched when conjugated with gold nanoparticles.
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    ABSTRACT: Several reports have demonstrated the anticancer activities of plumbagin, a naphthoquinone derivative isolated from plants belonging to Plumbaginaceae family. However, to the best of our knowledge, there are no reports which describe gold nanoconjugation with plumbagin, even though plumbagin is considered to be a promising therapeutic agent. In this report, we demonstrate the fabrication and characterization of gold nanoparticles conjugated with plumbagin (AuPB) that can reduce the toxicity of the latter, and their capacity for cellular localization and generation of reactive oxygen species. The anticancer activity and ability of plumbagin to produce reactive oxygen species was studied and compared with that of bromoderivatives of 1,4 naphthoquinones such as 2-bromo-1,4-naphthoquinone (2-BNQ) and 2,3-dibromo-1, 4-naphthoquinone (2,3-DBNQ) and their gold nanoconjugates. Plumbagin and bromoderivatives of 1,4 naphthoquinones in the form of gold nanoconjugates showed reduced cytotoxicity and apoptosis compared with the pristine compounds, ie, plumbagin, 2-BNQ, and 2,3-DBNQ. Interestingly, we observed that the gold nanoparticles could quench the reactive oxygen species-generating capacity of plumbagin, 2-BNQ, and 2,3-BNQ, which is one of the main mechanisms of action of the naphthoquinones. Therefore, it can be concluded that conjugation with gold nanoparticles can reduce the cytotoxicity of these compounds.
    International Journal of Nanomedicine 01/2011; 6:2113-22. · 3.13 Impact Factor

Keywords

3)H-labelled FA
 
anticancer therapy
 
core side effect issues
 
drug delivery
 
folic acid
 
gold nanoconjugates
 
gold nanoparticles
 
mercapto-polyethylene glycol
 
molecular weight
 
ovarian cancer
 
ovarian cancer cell lines
 
ovarian cancers
 
ovarian surface epithelial
 
platinum content
 
potential therapeutic application
 
radioactivity measurement
 
release profile
 
scintillation counter
 
Transmission electron microscopy
 
UV-Visible spectroscopy