Evaluation of a novel biocompatible magnetic nanomedicine based on beta-cyclodextrin, loaded doxorubicin-curcumin for overcoming chemoresistance in breast cancer

• Published in: Artificial cells, nanomedicine, and biotechnology Vol. 46; no. sup2; pp. 207 - 216
• Main Authors: Rastegar, Roghayeh, Akbari Javar, Hamid, Khoobi, Mehdi, Dehghan Kelishadi, Poua, Hossein Yousefi, Gholam, Doosti, Mahmoud, Hossien Ghahremani, Mohammad, Shariftabrizi, Ahmad, Imanparast, Fatemeh, Gholibeglu, Elham, Gholami, Mahdi
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.01.2018; Taylor & Francis Ltd
• Subjects: Accumulation; Anticancer properties; Biocompatibility; Breast cancer; Breast carcinoma; Cancer; Chemoresistance; Confocal microscopy; Curcumin; Cyclodextrins; Cytotoxicity; Doxorubicin; Electrophoresis; enhanced permeability and retention effect; Gel electrophoresis; Glycoproteins; Hydroxyapatite; iron oxide nanoparticle; Magnetic permeability; Nanocomposites; nanomedicine; Nanoparticles; Nanotechnology; P-Glycoprotein; Permeability; Pharmacology; protein corona; Proteins; Sodium dodecyl sulfate; Sodium lauryl sulfate; Toxicity testing; Tumors; β-Cyclodextrin; nanomedicine; iron oxide nanoparticle; Chemoresistance; enhanced permeability and retention effect; protein corona
• ISSN: 2169-1401; 2169-141X
• DOI: 10.1080/21691401.2018.1453829

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.