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Docetaxel–Chitosan Nanoparticles for Breast Cancer Treatment: Cell Viability and Gene Expression Study Publisher Pubmed



Mirzaie ZH1 ; Irani S1 ; Mirfakhraie R2 ; Atyabi SM3 ; Dinarvand M4 ; Dinarvand R4, 5 ; Varshochian R4 ; Atyabi F4, 5
Authors
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Authors Affiliations
  1. 1. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
  2. 2. Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  3. 3. Department of Pilot Biotechnology, Pasteur Institute of Iran, Tehran, Iran
  4. 4. Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: Chemical Biology and Drug Design Published:2016


Abstract

Docetaxel acts through the inhibition of tubulin polymerization and reduction in the expression of BCL-2 gene. In this study, nanoparticles containing Docetaxel were prepared and their effects on the gene expression levels of BCL-2 and BAX genes were investigated. The drug was first conjugated to chitosan, and the nanoparticles were assembled in the presence of hyaluronic acid. Conjugations were confirmed by 1H-NMR, and the obtained nanoparticles were characterized by dynamic light scattering and SEM. Cytotoxicity of the nanoparticles, cellular uptake, and cell death were evaluated. Finally, the effect of nanoparticles on the expression of BAX and BCL-2 genes in MCF-7 cells were investigated through real-time PCR. The results revealed that the prepared NPs had spherical shape with narrow size distribution of <200 nm with positive zeta potentials. In vitro cytotoxicity of Cs nanoparticles and free Docetaxel investigations revealed that increasing the treatment time with nanoparticles led to decrease in the rate of cell viability. BAX and BCL-2 gene expressions were decreased in nanoparticle-treated cells in comparison with intact cells, while the BAX/BCL-2 ratio was significantly elevated compared with free drug-treated cells after 72 h. Docetaxel-conjugated NPs may offer a promising treatment with low off-target toxicity for breast cancer. © 2016 John Wiley & Sons A/S.