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

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.

SUBMITTER: Patra CR

PROVIDER: S-EPMC2860188 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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

Patra Chitta Ranjan CR Bhattacharya Resham R Mukherjee Priyabrata P

Journal of materials chemistry 20100101 3

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 ...[more]

PMID: 20436942

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Project description:BackgroundOvarian cancer is a significant cancer-related cause of death in women worldwide. The most used chemotherapeutic regimen is based on carboplatin (CBDCA). However, CBDCA resistance is the main obstacle to a better prognosis. An in vitro drug-resistant cell model would help in the understanding of molecular mechanisms underlying this drug-resistance phenomenon. The aim of this study was to characterize cellular and molecular changes of induced CBDCA-resistant ovarian cancer cell line A2780.MethodsThe cell selection strategy used in this study was a dose-per-pulse method using a concentration of 100 μM for 2 h. Once 20 cycles of exposure to the drug were completed, the cell cultures showed a resistant phenotype. Then, the ovarian cancer cell line A2780 was grown with 100 μM of CBDCA (CBDCA-resistant cells) or without CBDCA (parental cells). After, a drug sensitivity assay, morphological analyses, cell death assays and a RNA-seq analysis were performed in CBDCA-resistant A2780 cells.ResultsMicroscopy on both parental and CBDCA-resistant A2780 cells showed similar characteristics in morphology and F-actin distribution within cells. In cell-death assays, parental A2780 cells showed a significant increase in phosphatidylserine translocation and caspase-3/7 cleavage compared to CBDCA-resistant A2780 cells (P < 0.05 and P < 0.005, respectively). Cell viability in parental A2780 cells was significantly decreased compared to CBDCA-resistant A2780 cells (P < 0.0005). The RNA-seq analysis showed 156 differentially expressed genes (DEGs) associated mainly to molecular functions.ConclusionCBDCA-resistant A2780 ovarian cancer cells is a reliable model of CBDCA resistance that shows several DEGs involved in molecular functions such as transmembrane activity, protein binding to cell surface receptor and catalytic activity. Also, we found that the Wnt/β-catenin and integrin signaling pathway are the main metabolic pathway dysregulated in CBDCA-resistant A2780 cells.

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

Publications

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

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