journal article·2011-03

Doxorubicin delivered to MCF-7 cancer cells by superparamagnetic iron oxide nanoparticles: effects on subcellular distribution and cytotoxicity

E. Munnier, S. Cohen-Jonathan, K. Hervé, C. Linassier, M. Soucé, P. Dubois, I. Chourpa

Journal of Nanoparticle Research· Volume 13· Issue 3
Publisher page

Abstract

The clinical use of the anticancer drug doxorubicin (DOX) is limited by strong side effects and phenomena of cell resistance. Drug targeting by binding DOX to nanoparticles could overcome these limitations. We recently described a method to associate DOX to superparamagnetic iron oxide nanoparticles (SPION) in view of magnetic drug targeting (Munnier et al. in Int J Pharm 363:170–176, 2008). DOX is bound to the nanoparticle surface through a pre-formed DOX–Fe2+ complex. The DOX-loaded SPION present interesting properties in terms of drug loading and biological activity in vitro. The purpose of this study is to explore the possible mechanisms of the in vitro cytotoxicity of DOX-loaded SPION. The uptake of SPION was followed qualitatively by conventional optical microscopy after Prussian blue staining and quantitatively by iron determination by atomic absorption spectroscopy. The subcellular distribution of intrinsically fluorescent DOX was followed by confocal spectral imaging (CSI) and the subsequent cytotoxicity by the MTT method. We reveal modifications of DOX intracellular interactions for SPION-delivered drug and increased cytotoxicity. These results are discussed in terms of internalization route of the drug and of a potential role of iron oxide nanoparticles in the observed cytotoxicity.
Source: openaire · Quality: candidate unverified · Source record ↗

Research context

OpenAlex topics: Nanoparticle-Based Drug Delivery · Characterization and Applications of Magnetic Nanoparticles · Iron oxide chemistry and applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (58)

Show source-provided references
1. Alexiou C, Arnold W, Klein RJ, Parak FG, Hulin P, Bergemann C, Erhardt W, Wagenpfeil S, Lübbe AS (2000) Locoregional cancer treatment with magnetic drug targeting. Cancer Res 60:6641–6648
2. Anderson AB, Gergen J, Arriaga EA (2002) Detection of doxorubicin and metabolites in cell extracts and in single cells by capillary electrophoresis with laser-induced fluorescence detection. J Chromatogr B Anal Technol Biomed Life Sci 769:97–10610.1016/S1570-0232(01)00633-X ↗
3. Apopa PL, Qian Y, Shao R, Lan Gua N, Schwegler-Berry N, Pacurari M, Porter D, Shi X, Vallyathan V, Castranova V, Flynn DC (2009) Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodelling. Part fibre toxicol 6:1–1410.1186/1743-8977-6-1 ↗
4. Aroui S, Brahim S, De Waard M, Bréard J, Kenani A (2009) Efficient induction of apoptosis dy doxorubicin coupled to cell-penetrating peptides compared to unconjugated doxorubicin in the human breast cancer cell line MDA-MB 231. Cancer Lett 285:28–3810.1016/j.canlet.2009.04.044 ↗
5. Aroui S, Brahim S, Kenani A (2010) Cytotoxicity, intracellular distribution and uptake of doxorubicin and doxorubicin coupled to cell penetrating peptides in different cell lines: a comparative study. BBRC. doi: 10.1016/j.bbrc.2009.11.07310.1016/j.bbrc.2009.11.073 ↗
6. Auffan M, Rose J, Wiesner MR, Bottero JY (2009) Chemical stability of metallic nanoparticles: a parameter controlling their potential cellular toxicity in vitro. Environ Pollut 157:1127–113310.1016/j.envpol.2008.10.002 ↗
7. Belhoussine R, Morjani H, Millot JM, Sharonov S, Manfait M (1998) Microspectrofluorometry reveals specific anthracycline accumulation in cytoplasmic organelles of multidrug-resistant cancer cells. J Histochem Cytochem 46:1369–137610.1177/002215549804601205 ↗
8. Choi SJ, Oh JM, Choy JH (2009) Toxicological effects of inorganic nanoparticles on human lung cancer A549 cells. J Inorg Biochem 103:463–47110.1016/j.jinorgbio.2008.12.017 ↗
9. Chourpa I, Douziech-Eyrolles L, Ngaboni Okassa L, Fouquenet JF, Cohen-Jonathan S, Soucé M, Marchais H, Dubois P (2005) Molecular composition of iron oxide nanoparticles, precursors for magnetic drug targeting, as characterized by confocal Raman microspectroscopy. Analyst 130:1395–140310.1039/b419004a ↗
10. Conner SD, Schmid SL (2003) Regulated portals of entry into the cell. Nature 422:37–4410.1038/nature01451 ↗
11. del Pozo-Rodríguez A, Pujals S, Delgado D, Solinís MA, Gascón AR, Giralt E, Pedraz JL (2009) A proline-rich peptide improves cell transfection of solid lipid nanoparticle-based non-viral vectors. J Control Release 133:52–5910.1016/j.jconrel.2008.09.004 ↗
12. Demaurex N, Grinstein S (2006) Measurements of endosomal pH in live cells by dual excitation fluorescence imaging. In: Cell Biol, 3rd edn. pp 163–16910.1016/B978-012164730-8/50144-1 ↗
13. Donaldson K, Stone V, Clouter A, Renwick L, MacNee W (2001) Ultrafine particles. Occup Environ Med 58:211–21610.1136/oem.58.3.211 ↗
14. Douziech-Eyrolles L, Marchais H, Hervé K, Munnier E, Soucé M, Linassier C, Dubois P, Chourpa I (2007) Nanovectors for anticancer agents based on superparamagnetic iron oxide nanoparticles. Int J Nanomed 2(4):541–550
15. Ebbesen P, Pettersen EO, Gorr TA, Jobst G, Williams K, Kieninger J, Wenger RH, Pastorekova S, Dubois L, Lambin P, Wouters BG, Van Den Beucken T, Supuran CT, Poellinger L, Ratcliffe P, Kanopka A, Görlach A, Gasmann M, Harris AL, Maxwell P, Scozzafava A (2009) Taking advantage of tumor cell adaptations to hypoxia for developing new tumor markers and treatment strategies. J Enzyme Inhibit Med Chem 24(1):1–3910.1080/14756360902784425 ↗
16. Ehrenberg MS, Friedman AE, Finkelstein JN, Oberdörster G, McGrath JL (2009) The influence of protein adsorption on nanoparticle association with cultured endothelial cells. Biomaterials 30:603–61010.1016/j.biomaterials.2008.09.050 ↗
17. Engin K, Leeper DB, Cater JR, Thistlethwaite AJ, Tupchong L, McFarlane JD (1995) Extracellular pH distribution in human tumors. Int J Hypertherm 11:211–21610.3109/02656739509022457 ↗
18. Fiallo MML, Garnier-Suillerot A, Matzanke B, Kozlowski H (1999) How Fe3+ binds anthracycline antitumour compounds. The myth and the reality of a chemical sphinx. J Inorg Biochem 75:105–11510.1016/S0162-0134(99)00040-9 ↗
19. Gabrielson NP, Pack DW (2009) Efficient polyethylenimine-mediated gene delivery proceeds via a caveolar pathway in HeLa cells. J Control Release 136:54–6110.1016/j.jconrel.2009.02.003 ↗
20. Gallois L, Fiallo M, Laigle A, Priebe W, Garnier-Suillerot A (1996) The overall partitioning of anthracyclines into phosphatidyl-containing model membranes depends neither on the drug charge nor the presence of anionic phospholipids. Eur J Biochem 241:879–88710.1111/j.1432-1033.1996.00879.x ↗
21. Ge Y, Zhang Y, Xia J, He S, Nie F, Gu N (2009) Effect of surface charge and agglomerate degree of magnetic iron nanoparticles on KB cellular uptake in vitro. Colloid Surf B Biointerfaces 73:294–30110.1016/j.colsurfb.2009.05.031 ↗
22. Glait C, Ravid D, Lee SW, Liscovitch M, Werner H (2006) Caveolin-1 controls BRCA1 gene expression and cellular localization in human breast cancer cells. FEBS Lett 580:5268–527410.1016/j.febslet.2006.08.071 ↗
23. Gumbleton M, Hollins AJ, Omidi Y, Campbell L, Taylor G (2003) Targeting caveolae for vesicular drug transport. J control release 87:139–15110.1016/S0168-3659(02)00358-9 ↗
24. Hande KR (2006) Topoisomerase II inhibitors. Update Cancer Therap 1:3–1510.1016/j.uct.2006.04.001 ↗
25. Hovorka O, St’astny M, Etrych T, Subr V, Strohalm J, Ulbrich K, Rihova B (2002) Differences in the intracellular fate of free and polymer-bound doxorubicin. J Control Release 80:101–11710.1016/S0168-3659(02)00016-0 ↗
26. Jain TK, Morales MA, Sahoo SK, Leslie-Pelecky DL, Labhasetwar V (2005) Iron oxide nanoparticles for sustained delivery of anticancer agents. Mol Pharm 2:194–20510.1021/mp0500014 ↗
27. Jing Y, Naladri M, Williams PS, Mayorga M, Penn MS, Chalmers JJ, Zborowski M (2008) Quantitative intracellular magnetic nanoparticles uptake measured by live cell magnetophoresis. FASEB J 22:4239–424710.1096/fj.07-105544 ↗
28. Jones CF, Grainger DW (2009) In vitro assessments of nanomaterial toxicity. Adv Drug Deliv Rev 61:438–45610.1016/j.addr.2009.03.005 ↗
29. Karlsson HL, Cronholm P, Gustafsson J, Möller L (2008) Copper oxide nanoparticles are highly toxic: a comparison between metal oxide nanoparticles and carbon nanotubes. Chem Res Toxicol 21:1726–173210.1021/tx800064j ↗
30. Karukstis K, Thompson EHZ, Whiles JA, Rosenfeld RJ (1998) Deciphering the fluorescence signature of daunomycin and doxorubicin. Biophys Chem 73:249–26310.1016/S0301-4622(98)00150-1 ↗
31. Kataoka K, Matsumoto T, Yokoyama M, Okano T, Sakurai Y, Fukushima S, Okamoto K, Kwon GS (2000) Doxorubicin-loaded poly(ethylene glycol)-poly(beta-benzyl-L-aspartate) copolymer micelles: their pharmaceutical characteristics and biological significance. J Control Release 64:143–15310.1016/S0168-3659(99)00133-9 ↗
32. Leonard RCF, Williams S, Tulpule A, Levine AM, Oliveros S (2009) Improving the therapeutic index of anthracyclines chemotherapy: focus on liposomal doxorubicin (Myocet®). Breast 18:218–22410.1016/j.breast.2009.05.004 ↗
33. Lewinski N, Colvin V, Drezek R (2008) Cytotoxicity of nanoparticles. Small 4(1):26–4910.1002/smll.200700595 ↗
34. Lübbe AS, Bergemann C, Riess H, Schriever F, Reichardt P, Possinger K, Matthias M, Dorken B, Herrmann F, Gurtler R, Hohenberger P, Haas N, Sohr R, Sander B, Lemke AJ, Ohlendorf D, Huhnt W, Huhn D (1996) Clinical experiences with magnetic drug targeting: a phase I study with 4′-epidoxorubicin in 14 patients with advanced solid tumors. Cancer Res 56:4686–4693
35. Mahmoudi M, Simchi A, Imani M, Shokrgozar MA, Milani AS, Häfeli UO, Troeve P (2009) A new approach for the in vitro identification of the cytotoxicity of Superparamagnetic iron oxide nanoparticles. Colloid Surf B Biointerfaces 75:300–30910.1016/j.colsurfb.2009.08.044 ↗
36. Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L (2004) Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 56:185–22910.1124/pr.56.2.6 ↗
37. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–6310.1016/0022-1759(83)90303-4 ↗
38. Mudhakir D, Akita H, Tan E, Harashima H (2008) A novel IRQ ligand-modified nano-carrier targeted to a unique pathway of caveolar endocytic pathway. J Control Release 125(2):164–17310.1016/j.jconrel.2007.10.020 ↗
39. Munnier E, Tewes F, Cohen-Jonathan S, Linassier C, Douziech-Eyrolles L, Marchais H, Soucé M, Hervé K, Dubois P, Chourpa I (2007) On the interaction of doxorubicin with oleate ions: fluorescence spectroscopy and liquid-liquid extraction study. Chem Pharm Bull 55:1006–101010.1248/cpb.55.1006 ↗
40. Munnier E, Cohen-Jonathan S, Linassier C, Douziech-Eyrolles L, Marchais H, Soucé M, Hervé K, Dubois P, Chourpa I (2008) Novel method of doxorubicin—SPION reversible association for magnetic drug targeting. Int J Pharm 363:170–17610.1016/j.ijpharm.2008.07.006 ↗
41. Mykhaylyk O, Dudchenko N, Dudchenko A (2005) Doxorubicin magnetic conjugate targeting upon intravenous injection into mice: high gradient magnetic field inhibits the clearance of nanoparticles from the blood. J Magn Magn Mater 293:473–48210.1016/j.jmmm.2005.01.063 ↗
42. Pelkmans L, Helenius A (2003) Insider information: what viruses tell us about endocytosis. Curr Opin Cell Biol 15:414–42210.1016/S0955-0674(03)00081-4 ↗
43. Pradhan P, Giri J, Banerjee R, Bellare J, Bahadur D (2007) Cellular interactions of lauric acid and dextran-coated magnetite nanoparticles. J Magn Magn Mater 311:282–28710.1016/j.jmmm.2006.10.1181 ↗
44. Pütz G, Schmah O, Eckes J, Hug MJ, Winkler K (2009) Controlled application and scheduled removal of nanoparticle based chemotherapeutics (CARL) will reduce dose limiting adverse events in anticancer chemotherapy. Med Hypothesis doi: 10.1016/j.mehy.2008.11.02710.1016/j.mehy.2008.11.027 ↗
45. Raghunand N, Mahoney BP, Gillies RJ (2003) Tumor acidity, ion trapping and chemotherapeutics. II. pH-dependent partition coefficients predict importance of ion trapping on pharmacokinetics of weakly basic chemotherapeutic agents. Biochem Pharmacol 66:1219–122910.1016/S0006-2952(03)00468-4 ↗
46. Razzano G, Rizzo V, Vigevani A (1990) Determination of phenolic ionization constants of anthracyclines with modified substitution pattern of anthraquinone chromophore. IL Farmaco 45:215–222
47. Rudge SR, Kurtz TL, Vessely CR, Catterall LG, Williamson DL (2000) Preparation, characterization, and performance of magnetic iron-carbon composite microparticles for chemotherapy. Biomaterials 21:1411–142010.1016/S0142-9612(00)00006-5 ↗
48. Schöpf B, Neuberger T, Schulze K, Petri A, Chastellain M, Hoffmann M, Hoffmann H, von Rechenberg B (2005) Methodology description of cellular uptake of PVA coated superparamagnetic iron oxide nanoparticles (SPION) in synovial cells of sheep. J Magn Magn Mater 293:411–41810.1016/j.jmmm.2005.02.076 ↗
49. Sharonov S, Chourpa I, Morjani H, Nabiev I, Manfait M, Feofanov A (1994) Confocal spectral imaging analysis in studies of the spatial distribution of antitumor drugs within living cancer cells. Anal Chim Acta 290:40–4710.1016/0003-2670(94)80038-3 ↗
50. Shen Y, Tang H, Zhan Y, Van Kirk EA, Murdoch WJ (2009) Degradable poly(β-amino ester) nanoparticles for cancer cytoplasmic drug delivery. Nanomedicine doi: 10.1016/j.nano.2008.09.00310.1016/j.nano.2008.09.003 ↗
51. Vibet S, Mahéo K, Goré J, Dubois P, Bougnoux P, Chourpa I (2007) Differential subcellular distribution of mitoxantrone in relation to chemosensitization in two human breast cancer cell lines. Drug Metab Disp 35:822–82810.1124/dmd.106.013474 ↗
52. Vieseh O, Gunn J, Zhang M (2009) Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging. Adv drug deliv rev. doi: 10.1016/j.addr.2009.11.00210.1016/j.addr.2009.11.002 ↗
53. Wilhelm C, Gazeau F (2008) Universal cell labelling with anionic magnetic nanoparticles. Biomaterials 29:3161–317410.1016/j.biomaterials.2008.04.016 ↗
54. Wilhelm C, Billotey C, Roger J, Pons JN, Bacri JC, Gazeau F (2003) Intracellular uptake of anionic superparamagnetic nanoparticles as a function of their surface coating. Biomaterials 24:1001–101110.1016/S0142-9612(02)00440-4 ↗
55. Xiong XB, Ma Z, Lai R, Lavasanifar A (2010) The therapeutic response to multifunctional polymeric nano-conjugates in the targeted cellular and subcellular delivery of doxorubicin. Biomaterials 31:757–76810.1016/j.biomaterials.2009.09.080 ↗
56. Zhang J, Misra RDK (2007) Magnetic drug-targeting carrier encapsulated with thermosensitive smart polymer: core-shell nanoparticles carrier and drug release response. Acta Biomater 3:838–85010.1016/j.actbio.2007.05.011 ↗
57. Zhang Y, Yang M, Portney NG, Cui D, Budak G, Ozbay E, Ozkan M, Ozkan CS (2008) Zeta potential: a surface electrical characteristic to probe the interaction of nanoparticles with normal and cancer human breast epithelial cells. Biomed Microdevices 10:321–32810.1007/s10544-007-9139-2 ↗
58. Zhang X, Meng L, Lu Q, Fei Z, Dyson P (2009) Targeted and controlled release of doxorubicin to cancer cells using modified single wall carbon nanotubes. Biomaterials 30:6041–604710.1016/j.biomaterials.2009.07.025 ↗