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In vitro cytotoxicity analysis of doxorubicin-loaded/superparamagnetic iron oxide colloidal nanoassemblies on MCF7 and NIH3T3 cell lines

. 2015 ; 10 () : 949-61. [epub] 20150129

Language English Country New Zealand Media electronic-ecollection

Document type Journal Article, Research Support, Non-U.S. Gov't

One of the promising strategies for improvement of cancer treatment is based on magnetic drug delivery systems, thus avoiding side effects of standard chemotherapies. Superparamagnetic iron oxide (SPIO) nanoparticles have ideal properties to become a targeted magnetic drug delivery contrast probes, named theranostics. We worked with SPIO condensed colloidal nanocrystal clusters (MagAlg) prepared through a new soft biomineralization route in the presence of alginate as the polymeric shell and loaded with doxorubicin (DOX). The aim of this work was to study the in vitro cytotoxicity of these new MagAlg-DOX systems on mouse fibroblast and breast carcinoma cell lines. For proper analysis and understanding of cell behavior after administration of MagAlg-DOX compared with free DOX, a complex set of in vitro tests, including production of reactive oxygen species, comet assay, cell cycle determination, gene expression, and cellular uptake, were utilized. It was found that the cytotoxic effect of MagAlg-DOX system is delayed compared to free DOX in both cell lines. This was attributed to the different mechanism of internalization of DOX and MagAlg-DOX into the cells, together with the fact that the drug is strongly bound on the drug nanocarriers. We discovered that nanoparticles can attenuate or even inhibit the effect of DOX, particularly in the tumor MCF7 cell line. This is a first comprehensive study on the cytotoxic effect of DOX-loaded SPIO compared with free DOX on healthy and cancer cell lines, as well as on the induced changes in gene expression.

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Lüpertz R, Wätjen W, Kahl R, Chovolou Y. Dose- and time-dependent effects of doxorubicin on cytotoxicity, cell cycle and apoptotic cell death in human colon cancer cells. Toxicology. 2010;271:115–121. PubMed

Gautier J, Munnier E, Paillard A, et al. A pharmaceutical study of doxorubicin-loaded PEGylated nanoparticles for magnetic drug targeting. Int J Pharm. 2012;424:16–25. PubMed

Lai JR, Chang YW, Yen HC, et al. Multifunctional doxorubicin/superparamagnetic iron oxide-encapsulated pluronic F127 micelles used for chemotherapy/magnetic resonance imaging. J Appl Phys. 2010;107:09B318.

Liao C, Sun Q, Liang B, Shen J, Shuai X. Targeting EGFR-overexpressing tumor cells using Cetuximab-immunomicelles loaded with doxorubicin and superparamagnetic iron oxide. Eur J Radiol. 2011;80:699–705. PubMed

Fan CH, Ting CY, Lin HJ, et al. SPIO-conjugated, doxorubicin-loaded microbubbles for concurrent MRI and focused-ultrasound enhanced brain-tumor drug delivery. Biomaterials. 2013;34:3706–3715. PubMed

Mahmoudi M, Simchi A, Imani M. Cytotoxicity of uncoated and polyvinyl alcohol coated superparamagnetic iron oxide nanoparticles. J Phys Chem C. 2009;113:9573–9580.

Bulte JWM, Kraitchman DL. Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed. 2004;17:484–499. PubMed

Kievit FM, Wang FY, Fang C, et al. Doxorubicin loaded iron oxide nanoparticles overcome multidrug resistance in cancer in vitro. J Control Release. 2011;152:76–83. PubMed PMC

Zhu L, Wang D, Wei X, et al. Multifunctional pH-sensitive superparamagnetic iron-oxide nanocomposites for targeted drug delivery and MR imaging. J Control Release. 2013;169:228–238. PubMed

Corot C, Robert P, Ideé JM, Port M. Recent advances in iron oxide nanocrystal technology for medical imaging. Adv Drug Deliver Rev. 2006;58:1471–1504. PubMed

Javid A, Ahmadian S, Saboury AA, Kalantar SM, Rezaei-Zarchi S, Shahzad S. Biocompatible APTES – PEG modified magnetite nanoparticles: effective carriers of antineoplastic agents to ovarian cancer. Appl Biochem Biotechnol. 2014;173:36–54. PubMed

Yang X, Grailer JJ, Rowland IJ, et al. Multifunctional SPIO/DOX-loaded wormlike polymer vesicles for cancer therapy and MR imaging. Biomaterials. 2010;31:9065–9073. PubMed

Yang X, Chen Y, Yuan R, et al. Folate-encoded and Fe3O4-loaded polymeric micelles for dual targeting of cancer cells. Polymer. 2008;49:3477–3485.

Yang HM, Oh BC, Kim JH, et al. Multifunctional poly (aspartic acid) nanoparticles containing iron oxide nanocrystals and doxorubicin for simultaneous cancer diagnosis and therapy. Colloids Surf A Physicochem Eng Asp. 2011;391:208–215.

Zoppellaro G, Argiris KN, Polakova K, et al. Theranostics of epitaxially condensed colloidal nanocrystal clusters, through a soft biomineralization route. Chem Mater. 2014;26:2062–2074.

Tomankova K, Kejlova K, Binder S, et al. In vitro cytotoxicity and phototoxicity study of cosmetics colorants. Toxicol In Vitro. 2011;25:1242–1250. PubMed

Al Faraj A. Preferential magnetic nanoparticle uptake by bone marrow derived macrophages sub-populations: effect of surface coating on polarization, toxicity, and in vivo MRI detection. J Nanopart Res. 2013;15:1797.

Hong SCH, Lee JH, Lee J, et al. Subtle cytotoxicity and genotoxicity differences in superparamagnetic iron oxide nanoparticles coated with various functional groups. Int J Nanomed. 2011;6:3219–3231. PubMed PMC

Chekhun VF, Todor IN, Lukyanova NY, et al. The use of nanoferromagnetics to increase the cytotoxic effect of antitumor drugs. Exp Oncol. 2009;31:163–167. PubMed

Kuznetsov AV, Margreiter R, Amberger A, Saks V, Grimm M. Changes in mitochondrial redox state, membrane potential and calcium precede mitochondrial dysfunction in doxorubicin-induced cell death. Biochim Biophys Acta. 2011;1813:1144–1152. PubMed

Ishikawa K, Ishii H, Saito T. DNA damage-dependent cell cycle checkpoints and genomic stability. DNA Cell Biol. 2006;25:406–411. PubMed

Maeng JH, Lee DH, Jung KH, et al. Multifunctional doxorubicin loaded superparamagnetic iron oxide nanoparticles for chemotherapy and magnetic resonance imaging in liver cancer. Biomaterials. 2010;31:4995–5006. PubMed

Ruhdorfer S, Sanovic R, Sander V, Krammer B, Verwanger T. Gene expression profiling of the human carcinoma cell line A-431 after 5-aminolevulinic acid-based photodynamic treatment. Int J Oncol. 2007;30:1253–1262. PubMed

Sanovic R, Krammer B, Grumboeck S, Verwanger T. Time-resolved gene expression profiling of human squamous cell carcinoma cells during the apoptosis process induced by photodynamic treatment with hypericin. Int J Oncol. 2009;35:921–939. PubMed

Hekmat A, Saboury AA, Divsalar A. The effects of silver nanoparticles and doxorubicin combination on DNA structure and its antiproliferative effect against T47D and MCF7 cell lines. J Biomed Nanotechnol. 2012;8:968–982. PubMed

Hekmat A, Saboury AA, Divsalar A, Seyedarabi A. Structural effects of TiO2 nanoparticles and doxorubicin on DNA and their antiproliferative roles in T47D and MCF7 cells. Anticancer Agents Med Chem. 2013;13:932–951. PubMed

Malekinejad H, Janbaz-Acyabar H, Razi M, Varasteh S. Preventive and protective effects of silymarin on doxorubicin-induced testicular damages correlate with changes in c-myc gene expression. Phytomedicine. 2012;15:1077–1084. PubMed

Johnson NA, Slack GW, Savage KJ, et al. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012;30:3452–3459. PubMed PMC

Florou D, Patsis C, Ardavanis A, Scorilas A. Effect of doxorubicin, oxaliplatin, and methotrexate administration on the transcriptional activity of BCL-2 family gene members in stomach cancer cells. Cancer Biol Ther. 2013;14:587–596. PubMed PMC

Huang L, Perrault C, Coelho-Martins J, et al. Induction of acquired drug resistance in endothelial cells and its involvement in anticancer therapy. J Hematol Oncol. 2013;6:49. PubMed PMC

Jardim BV, Moschetta MG, Leonel C, et al. Glutathione and glutathione peroxidase expression in breast cancer: an immunohistochemical and molecular study. Oncol Rep. 2013;13:1119–1128. PubMed

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