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Evaluation of a Novel Biocompatible Magnetic Nanomedicine Based on Beta-Cyclodextrin, Loaded Doxorubicin-Curcumin for Overcoming Chemoresistance in Breast Cancer Publisher Pubmed



Rastegar R1 ; Akbari Javar H1, 2 ; Khoobi M3 ; Dehghan Kelishadi P3 ; Hossein Yousefi G4 ; Doosti M5 ; Hossien Ghahremani M6 ; Shariftabrizi A7 ; Imanparast F8 ; Gholibeglu E9 ; Gholami M6
Authors
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Authors Affiliations
  1. 1. Department of Pharmaceutical Biomaterials, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Pharmaceutics, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Medical Biomaterials Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pharmaceutics, Shiraz University of Medical Sciences, Shiraz, Iran
  5. 5. Department of Clinical Biochemistry, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Pharmaceutical Toxicology, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
  8. 8. Department of Medical Biochemistry, Irak University of Medical Sciences, Iran, Iraq
  9. 9. Department of Organic Chemistry, Zanjan University, Zanjan, Iran

Source: Artificial Cells# Nanomedicine and Biotechnology Published:2018


Abstract

Codelivery of chemo-sensitizers with chemotherapeutics using combo nanomedicine is a promising platform for overcoming chemoresistance in breast cancer. However, tumor accumulation of nano-carriers based on enhanced permeability and retention (EPR) effect is confounded by heterogeneity in tumor microenvironment. Adsorption of protein corona on surface of nanoparticle boost up clearance by reticulo-endothelial system. In this study, a surface functionalized magnetic nanocomposite (NC) for codelivery of doxorubicin (DOX) and curcumin (CUR) is developed. NCs were coated with hydroxyapatite and were also cross linked with β-cyclodextrin. NCs efficiently encapsulated DOX and CUR. Release of CUR and DOX were in a sustained pH-depended pattern. β-cyclodextrin functionalization reduced protein corona according sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis. As shown by flowcytometric and confocal microscopy analyses, NCs internalized efficiently by human breast carcinoma cells MCF-7 and adriamycin resistant MCF-7 (MCF-7/adr) cells. 3–(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) test demonstrated superior cytotoxicity of DOX-CUR loaded NCs. Anti-tumor efficacy analyses confirmed reduction in relative tumor volume size (RTV%) compared to control group. Western blot analyses demonstrated marginal CUR mediated P-glycoprotein (P-gp) down regulation. DOX-CUR loaded NCs efficiently accumulated into the tumor via external magnet guidance. Nevertheless, the increased tumor accumulation did not correlate with pharmacologic responses such as RTV% and significant superiority over free DOX was not observed. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.
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