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Magnetite nanoparticles functionalized with α-tocopheryl succinate (α-TOS) promote selective cervical cancer cell death

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Abstract

The vitamin E analog α-tocopheryl succinate (α-TOS) selectively induces apoptosis in several cancer cells, but it is sensitive to esterases present in cervical cancer cells. Magnetite nanoparticles (Nps) were prepared by a reduction–coprecipitation method; their surface was silanized and conjugated to α-TOS to enhance its resistance. Morphology, size, and crystal structure were analyzed by scanning electron microscopy, transmission electron microscopy, and selected area electron diffraction. Chemical composition was analyzed by energy-dispersive X-ray spectroscopy; functional groups were determined by Fourier transform infrared spectroscopy; and α-TOS content was estimated by thermogravimetric analysis. The cytotoxic activity of α-TOS-Nps was evaluated in non-malignant fibroblasts and cervical cancer cells by means of the colorimetric MTT viability test. Intracellular localization was identified by confocal laser scanning microscopy. Characterization of α-TOS-Nps revealed sphere-like Nps with 15 nm average size, formed by mineral and organic constituents with high stability. α-TOS-Nps were internalized in the nucleus and selectively affected the viability of cervical cancer cells in a dose- and time-dependent manner but were biocompatible with non-malignant fibroblasts. In conclusion, functionalization of magnetite Nps protected the cytotoxic activity of α-TOS in non-sensitive cervical cancer cells.

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References

  • Amstad E, Zurcher S, Mashaghi A, Wong J, Textor M, Reimhult E (2009) Surface functionalization of single superparamagnetic iron oxide nanoparticles for targeted magnetic resonance imaging. Small 5(11):1334–1342. doi:10.1002/smll.200801328

    Article  Google Scholar 

  • Amstad E, Textor M, Reimhult E (2011) Stabilization and functionalization of iron oxide nanoparticles for biomedical applications. Nanoscale 3(7):2819–2843. doi:10.1039/c1nr10173k

    Article  Google Scholar 

  • Anderson K, Simmons-Menchaca M, Lawson KA, Atkinson J, Sanders BG, Kline K (2004) Differential response of human ovarian cancer cells to induction of apoptosis by vitamin E succinate and vitamin E analogue, alpha-TEA. Cancer Res 64(12):4263–4269. doi:10.1158/0008-5472.can-03-2327

    Article  Google Scholar 

  • Baba D, Seiko Y, Nakanishi T, Zhang H, Arakaki A, Matsunaga T, Osaka T (2012) Effect of magnetite nanoparticles on living rate of MCF-7 human breast cancer cells. Colloids Surf B 95:254–257. doi:10.1016/j.colsurfb.2012.03.008

    Article  Google Scholar 

  • Cai W, Wan J (2007) Facile synthesis of superparamagnetic magnetite nanoparticles in liquid polyols. J Colloid Interface Sci 305(2):366–370. doi:10.1016/j.jcis.2006.10.023

    Article  Google Scholar 

  • Chen D, Tang Q, Li X, Zhou X, Zang J, Xue WQ, Xiang JY, Guo CQ (2012) Biocompatibility of magnetic Fe(3)O(4) nanoparticles and their cytotoxic effect on MCF-7 cells. Int J Nanomed 7:4973–4982. doi:10.2147/ijn.s35140

    Article  Google Scholar 

  • Choy JH, Shin J, Lim SY, Oh JM, Oh MH, Oh S (2010) Characterization and stability analysis of zinc oxide nanoencapsulated conjugated linoleic acid. J Food Sci 75(6):N63–N68. doi:10.1111/j.1750-3841.2010.01676.x

    Article  Google Scholar 

  • Daou TJ, Pourroy G, Bégin-Colin S, Grenèche JM, Ulhaq-Bouillet C, Legaré P, Bernhardt P, Leuvrey C, Rogez G (2006) Hydrothermal synthesis of monodisperse magnetite nanoparticles. Chem Mater 18(18):4399–4404. doi:10.1021/cm060805r

    Article  Google Scholar 

  • Dong LF, Jameson VJ, Tilly D, Cerny J, Mahdavian E, Marin-Hernandez A, Hernandez-Esquivel L, Rodriguez-Enriquez S, Stursa J, Witting PK, Stantic B, Rohlena J, Truksa J, Kluckova K, Dyason JC, Ledvina M, Salvatore BA, Moreno-Sanchez R, Coster MJ, Ralph SJ, Smith RA, Neuzil J (2011) Mitochondrial targeting of vitamin E succinate enhances its pro-apoptotic and anti-cancer activity via mitochondrial complex II. J Biol Chem 286(5):3717–3728. doi:10.1074/jbc.M110.186643

    Article  Google Scholar 

  • Dong LF, Grant G, Massa H, Zobalova R, Akporiaye E, Neuzil J (2012) Alpha-Tocopheryloxyacetic acid is superior to alpha-tocopheryl succinate in suppressing HER2-high breast carcinomas due to its higher stability. Int J Cancer 131(5):1052–1058. doi:10.1002/ijc.26489

    Article  Google Scholar 

  • Ghotbi MY, bin Hussein MZ (2012) Controlled release study of an anti-carcinogenic agent, gallate from the surface of magnetite nanoparticles. J Phys Chem Solids 73(7):936–942. doi:10.1016/j.jpcs.2012.02.031

    Google Scholar 

  • Gogvadze V, Norberg E, Orrenius S, Zhivotovsky B (2010) Involvement of Ca2 + and ROS in alpha-tocopheryl succinate-induced mitochondrial permeabilization. Int J Cancer 127(8):1823–1832. doi:10.1002/ijc.25204

    Article  Google Scholar 

  • Gu X, Song X, Dong Y, Cai H, Walters E, Zhang R, Pang X, Xie T, Guo Y, Sridhar R, Califano JA (2008) Vitamin E succinate induces ceramide-mediated apoptosis in head and neck squamous cell carcinoma in vitro and in vivo. Clin Cancer Res 14(6):1840–1848. doi:10.1158/1078-0432.ccr-07-1811

    Article  Google Scholar 

  • Gupta AK, Wells S (2004) Surface-modified superparamagnetic nanoparticles for drug delivery: preparation, characterization, and cytotoxicity studies. IEEE Trans Nanobiosci 3(1):66–73. doi:10.1109/tnb.2003.820277

    Article  Google Scholar 

  • Hultman KL, Raffo AJ, Grzenda AL, Harris PE, Brown TR, O’Brien S (2008) Magnetic resonance imaging of major histocompatibility class II expression in the renal medulla using immunotargeted superparamagnetic iron oxide nanoparticles. ACS Nano 2(3):477–484. doi:10.1021/nn700400h

    Article  Google Scholar 

  • Kanai K, Kikuchi E, Mikami S, Suzuki E, Uchida Y, Kodaira K, Miyajima A, Ohigashi T, Nakashima J, Oya M (2010) Vitamin E succinate induced apoptosis and enhanced chemosensitivity to paclitaxel in human bladder cancer cells in vitro and in vivo. Cancer Sci 101(1):216–223. doi:10.1111/j.1349-7006.2009.01362.x

    Article  Google Scholar 

  • Kim DH, Lee SH, Im KH, Kim KN, Kim KM, Shim IB, Lee MH, Lee YK (2006) Surface-modified magnetite nanoparticles for hyperthermia: preparation, characterization, and cytotoxicity studies. Curr Appl Phys 6:e242–e246. doi:10.1016/j.cap.2006.01.048

    Article  Google Scholar 

  • Kline K, Yu W, Sanders BG (2001) Vitamin E: mechanisms of action as tumor cell growth inhibitors. J Nutr 131(1):161S–163S

    Google Scholar 

  • Ma Y, Huang L, Song C, Zeng X, Liu G, Mei L (2010a) Nanoparticle formulation of poly(ε-caprolactone-co-lactide)-d-α-tocopheryl polyethylene glycol 1000 succinate random copolymer for cervical cancer treatment. Polymer 51(25):5952–5959. doi:10.1016/j.polymer.2010.10.029

    Article  Google Scholar 

  • Ma Y, Zheng Y, Liu K, Tian G, Tian Y, Xu L, Yan F, Huang L, Mei L (2010b) Nanoparticles of poly(lactide-co-glycolide)-d-a-tocopheryl polyethylene glycol 1000 succinate random copolymer for cancer treatment. Nanoscale Res Lett 5(7):1161–1169. doi:10.1007/s11671-010-9620-3

    Article  Google Scholar 

  • Mahmoudi M, Simchi A, Milani AS, Stroeve P (2009) Cell toxicity of superparamagnetic iron oxide nanoparticles. J Colloid Interface Sci 336(2):510–518. doi:10.1016/j.jcis.2009.04.046

    Article  Google Scholar 

  • Malafa MP, Fokum FD, Mowlavi A, Abusief M, King M (2002) Vitamin E inhibits melanoma growth in mice. Surgery 131(1):85–91

    Article  Google Scholar 

  • Min JH, Kim ST, Lee JS, Kim K, Wu JH, Jeong J, Song AY, Lee K-M, Kim YK (2011) Labeling of macrophage cell using biocompatible magnetic nanoparticles. J Appl Phys 109(7):07B309/1–07B309/3

    Article  Google Scholar 

  • Mohapatra S, Mallick SK, Maiti TK, Ghosh SK, Pramanik P (2007) Synthesis of highly stable folic acid conjugated magnetite nanoparticles for targeting cancer cells. Nanotechnology 18(38):385102

    Article  Google Scholar 

  • Neuzil J, Weber T, Gellert N, Weber C (2001) Selective cancer cell killing by alpha-tocopheryl succinate. Br J Cancer 84(1):87–89. doi:10.1054/bjoc.2000.1559

    Article  Google Scholar 

  • Nguyen TKT, Luke AWG (2010) Functionalisation of nanoparticles for biomedical applications. Nano Today 5:213–230. doi:10.1016/j.nantod.2010.05.003

    Article  Google Scholar 

  • Perez-Gonzalez T, Rodriguez-Navarro A, Jimenez-Lopez C (2011) Inorganic magnetite precipitation at 25 °C: a low-cost inorganic coprecipitation method. J Supercond Nov Magn 24(1–2):549–557. doi:10.1007/s10948-010-0999-y

    Article  Google Scholar 

  • Qu S, Yang H, Ren D, Kan S, Zou G, Li D, Li M (1999) Magnetite nanoparticles prepared by precipitation from partially reduced ferric chloride aqueous solutions. J Colloid Interface Sci 215(1):190–192. doi:10.1006/jcis.1999.6185

    Article  Google Scholar 

  • Ramesh V, Ravichandran P, Copeland CL, Gopikrishnan R, Biradar S, Goornavar V, Ramesh GT, Hall JC (2012) Magnetite induces oxidative stress and apoptosis in lung epithelial cells. Mol Cell Biochem 363(1–2):225–234. doi:10.1007/s11010-011-1174-x

    Article  Google Scholar 

  • Rivas J, Bañobre-López M, Piñeiro-Redondo Y, Rivas B, López-Quintela MA (2012) Magnetic nanoparticles for application in cancer therapy. J Magn Magn Mater 324(21):3499–3502. doi:10.1016/j.jmmm.2012.02.075

    Article  Google Scholar 

  • Rutnakornpituk M, Meerod S, Boontha B, Wichai U (2009) Magnetic core-bilayer shell nanoparticle: a novel vehicle for entrapment of poorly water-soluble drugs. Polymer 50(15):3508–3515. doi:10.1016/j.polymer.2009.06.015

    Article  Google Scholar 

  • Shen X-C, Fang X-Z, Zhou Y-H, Liang H (2004) Synthesis and characterization of 3-aminopropyltriethoxysilane-modified superparamagnetic magnetite nanoparticles. Chem Lett 33(11):1468–1469

    Article  Google Scholar 

  • Tomasetti M, Strafella E, Staffolani S, Santarelli L, Neuzil J, Guerrieri R (2010) Alpha-Tocopheryl succinate promotes selective cell death induced by vitamin K3 in combination with ascorbate. Br J Cancer 102(8):1224–1234. doi:10.1038/sj.bjc.6605617

    Article  Google Scholar 

  • Turanek J, Wang XF, Knotigova P, Koudelka S, Dong LF, Vrublova E, Mahdavian E, Prochazka L, Sangsura S, Vacek A, Salvatore BA, Neuzil J (2009) Liposomal formulation of alpha-tocopheryl maleamide: in vitro and in vivo toxicological profile and anticancer effect against spontaneous breast carcinomas in mice. Toxicol Appl Pharmacol 237(3):249–257. doi:10.1016/j.taap.2009.01.027

    Article  Google Scholar 

  • Vippola M, Falck GC, Lindberg HK, Suhonen S, Vanhala E, Norppa H, Savolainen K, Tossavainen A, Tuomi T (2009) Preparation of nanoparticle dispersions for in vitro toxicity testing. Hum Exp Toxicol 28(6–7):377–385. doi:10.1177/0960327109105158

    Article  Google Scholar 

  • Wu W, He Q, Jiang C (2008) Magnetic iron oxide nanoparticles: synthesis and surface functionalization strategies. Nanoscale Res Lett 3(11):397–415. doi:10.1007/s11671-008-9174-9

    Article  Google Scholar 

  • Zhang Y, Zhang J (2005) Surface modification of monodisperse magnetite nanoparticles for improved intracellular uptake to breast cancer cells. J Colloid Interface Sci 283(2):352–357. doi:10.1016/j.jcis.2004.09.042

    Article  Google Scholar 

  • Zhang Y, Kohler N, Zhang M (2002) Surface modification of superparamagnetic magnetite nanoparticles and their intracellular uptake. Biomaterials 23(7):1553–1561

    Article  Google Scholar 

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Acknowledgments

Authors are grateful to Francisco Ruiz for TEM support, Ma. Iracema Valeriano Arreola and Fidel Pacheco for TGA analysis, personal from CIBIOR for technical assistance. This study was supported by the SEP-CONACYT (Fondo de Investigación Científica Básica) Grant No. 154602. CIBIOR was supported by funds from the Mexican Institute for Social Security (CTFIS/10RD/12/2011). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflict of interest

The authors declare that there is no conflict of interest.

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Authors and Affiliations

  1. Departamento de Ciencias de la Salud, Universidad de las Américas Puebla (UDLAP), Oficina SL-305-A Ex-Hda. de Sta. Catarina Mártir, San Andrés Cholula, 72820, Puebla, Mexico

    Aracely Angulo-Molina, Miguel Ángel Méndez-Rojas & Teresa Palacios-Hernández

  2. Laboratorio de Inmunología, Centro de Investigación en Alimentación y Desarrollo, A.C., Hermosillo, Sonora, Mexico

    Aracely Angulo-Molina & Jesús Hernández

  3. Universidad Popular Autónoma del Estado de Puebla (UPAEP), Puebla, Mexico

    Teresa Palacios-Hernández

  4. Centro de Nanociencias y Nanotecnología (CNYN), Universidad Nacional Autónoma de México, Ensenada, BCN, Mexico

    Oscar Edel Contreras-López & Gustavo Alonso Hirata-Flores

  5. Centro de Investigación Biomédica de Oriente (CIBIOR), Instituto Mexicano del Seguro Social, Metepec, Puebla, Mexico

    Juan Carlos Flores-Alonso & Julio Reyes-Leyva

  6. Benemérita Universidad Autónoma de Puebla (BUAP), Puebla, Mexico

    Saul Merino-Contreras

  7. Departamento de Ciencias Químico-Biológicas, Universidad de Sonora, Hermosillo, Sonora, Mexico

    Olivia Valenzuela

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  1. Aracely Angulo-Molina
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  2. Miguel Ángel Méndez-Rojas
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  3. Teresa Palacios-Hernández
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  4. Oscar Edel Contreras-López
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  5. Gustavo Alonso Hirata-Flores
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  6. Juan Carlos Flores-Alonso
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  7. Saul Merino-Contreras
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  8. Olivia Valenzuela
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  9. Jesús Hernández
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Correspondence to Aracely Angulo-Molina or Julio Reyes-Leyva.

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Angulo-Molina, A., Méndez-Rojas, M.Á., Palacios-Hernández, T. et al. Magnetite nanoparticles functionalized with α-tocopheryl succinate (α-TOS) promote selective cervical cancer cell death. J Nanopart Res 16, 2528 (2014). https://doi.org/10.1007/s11051-014-2528-6

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