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The advance anticancer role of polymeric core-shell ZnO nanoparticles containing oxaliplatin in colorectal cancer
Authors:Negin Alavi  Parvaneh Maghami  Azar Fani Pakdel  Majid Rezaei  Amir Avan
Institution:1. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran;2. Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;3. Medical Toxicology Research Center, University of Medical Sciences, Mashhad, Iran

Department of Medical Biotechnology and Nanotechnology, School of Medicine, University of Medical Sciences, Mashhad, Iran

Nanotechnology & Catalysis Research Centre, Institute of Postgraduate Studies, University Malaya, Kuala Lumpur, Malaysia

Abstract:We evaluated the activity of core-shell ZnO nanoparticles (ZnO-NPs@polymer shell) containing Oxaliplatin via polymerization through in vitro studies and in vivo mouse models of colorectal cancer. ZnO NPs were synthesized in situ when the polymerization step was completed by co-precipitation. Gadolinium coordinated-ZnONPs@polymer shell (ZnO-Gd NPs@polymer shell) was synthesized by exploiting Gd's oxophilicity (III). The biophysical properties of the NPs were studied using powder X-ray diffraction (PXRD), Fourier transforms infrared spectroscopy, Ultraviolet-visible spectroscopy (UV-Vis), field emission electron microscopy (FESEM), transmission electron microscopy (TEM), atomic force microscopy, dynamic light scattering, and z-potential. (3-(4,5-Dimethylthiazol-2-yl)−2,5-diphenyltetrazolium bromide) (MTT) was used to determine the antiproliferative activity of ZnO-Gd-OXA. Moreover, a xenograft mouse model of colon cancer was exerted to survey its antitumor activity and effect on tumor growth. In the following, the model was also evaluated by histological staining (H-E; Hematoxylin & Eosin and trichrome staining) and gene expression analyses through the application of RT-PCR/ELISA, which included biochemical evaluation (MDA, thiols, SOD, CAT). The formation of ZnO NPs, which contained a crystallite size of 16.8 nm, was confirmed by the outcomes of the PXRD analysis. The Plate-like morphology and presence of Pt were obtained in EDX outcomes. TEM analysis displayed the attained ZnO NPs in a spherical shape and a diameter of 33 ± 8.5 nm, while the hydrodynamic sizes indicated that the particles were highly aggregated. The biological results demonstrated that ZnO-Gd-OXA inhibited tumor growth by inducing reactive oxygen species and inhibiting fibrosis, warranting further research on this novel colorectal cancer treatment agent.
Keywords:colorectal cancer  drug delivery  nanocomposite  tumor growth  ZnO
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