Advertisement

Effect of surface charge on the colloidal stability and in vitro uptake of carboxymethyl dextran-coated iron oxide nanoparticles

  • Vanessa Ayala
  • Adriana P. Herrera
  • Magda Latorre-Esteves
  • Madeline Torres-Lugo
  • Carlos RinaldiEmail author
Research Paper

Abstract

Nanoparticle physicochemical properties such as surface charge are considered to play an important role in cellular uptake and particle–cell interactions. In order to systematically evaluate the role of surface charge on the uptake of iron oxide nanoparticles, we prepared carboxymethyl-substituted dextrans with different degrees of substitution, ranging from 38 to 5 groups per chain, and reacted them using carbodiimide chemistry with amine–silane-coated iron oxide nanoparticles with narrow size distributions in the range of 33–45 nm. Surface charge of carboxymethyl-substituted dextran-coated nanoparticles ranged from −50 to 5 mV as determined by zeta potential measurements, and was dependent on the number of carboxymethyl groups incorporated in the dextran chains. Nanoparticles were incubated with CaCo-2 human colon cancer cells. Nanoparticle–cell interactions were observed by confocal laser scanning microscopy and uptake was quantified by elemental analysis using inductively coupled plasma mass spectroscopy. Mechanisms of internalization were inferred using pharmacological inhibitors for fluid-phase, clathrin-mediated, and caveola-mediated endocytosis. Results showed increased uptake for nanoparticles with greater negative charge. Internalization patterns suggest that uptake of the most negatively charged particles occurs via non-specific interactions.

Keywords

Iron oxide Dextran Surface charge Uptake Endocytosis 

Notes

Acknowledgments

This work was supported by the US NSF (CBET-0609117, OIA-0701525) and tNIH (1 R15 EB010228-01). We acknowledge the use of the Integrated Advanced Microscopy facility at the Cornell Center for Materials Research (CCMR) supported by the NSF-MRSEC program (DMR 0520404) and are grateful to Prof. Juan Hinestroza and Alejandra Andere for performing TEM measurements. We acknowledge the use of the UPRM microscopy facility and the help of Mr. Jose Almodóvar in the CLSM measurements.

Supplementary material

11051_2013_1874_MOESM1_ESM.doc (194 kb)
Supplementary material 1 (DOC 193 kb)

References

  1. Alhareth K, Vauthier C, Bourasset F, Gueutin C, Ponchel G, Moussa F (2012) Conformation of surface-decorating dextran chains affects the pharmacokinetics and biodistribution of doxorubicin-loaded nanoparticles. Eur J Pharm Biopharm 81(2):453–457CrossRefGoogle Scholar
  2. Arias JL, Lopez-Viota M, Saez-Fernandez E, Ruiz MA, Delgado AV (2011) Engineering of an antitumor (core/shell) magnetic nanoformulation based on the chemotherapy agent ftorafur. Colloids Surf A 384(1–3):157–163CrossRefGoogle Scholar
  3. Arnida, Janát-Amsbury MM, Ray A, Peterson CM, Ghandehari H (2011) Geometry and surface characteristics of gold nanoparticles influence their biodistribution and uptake by macrophages. Eur J Pharm Biopharm 77(3):417–423. doi: 10.1016/j.ejpb.2010.11.010 CrossRefGoogle Scholar
  4. Bahmani B, Gupta S, Upadhyayula S, Vullev VI, Anvari B (2011) Effect of polyethylene glycol coatings on uptake of indocyanine green loaded nanocapsules by human spleen macrophages in vitro. J Biomed Opt 16 (5). doi: 10.1117/1.3574761
  5. Bao N, Shen L, Wang Y, Padhan P, Gupta A (2007) A facile thermolysis route to monodisperse ferrite nanocrystals. J Am Chem Soc 129:12374–12375CrossRefGoogle Scholar
  6. Bhattacharya D, Sahu SK, Banerjee I, Das M, Mishra D, Maiti TK, Pramanik P (2011) Synthesis, characterization, and in vitro biological evaluation of highly stable diversely functionalized superparamagnetic iron oxide nanoparticles. J Nanopart Res 13(9):4173–4188. doi: 10.1007/s11051-011-0362-7 CrossRefGoogle Scholar
  7. Chao Y, Karmali PP, Simberg D (2012) Role of carbohydrate receptors in the macrophage uptake of dextran-coated iron oxide nanoparticles. Adv Exp Med Biol 733:115–123CrossRefGoogle Scholar
  8. Chaubet J, Maiga O, Mauray S, Jozefonvicz J (1995) Synthesis and structure-anticoagulant property relationships of functionalized dextrans. Carbohydr Polym 28:145–152CrossRefGoogle Scholar
  9. Chen J-P, Yang P-C, Ma Y-H, Lu Y-J (2011) Superparamagnetic iron oxide nanoparticles for delivery of tissue plasminogen activator. J Nanosci Nanotechnol 11(12):11089–11094CrossRefGoogle Scholar
  10. Cole AJ, David AE, Wang J, Galbán CJ, Hill HL, Yang VC (2011) Polyethylene glycol modified, cross-linked starch-coated iron oxide nanoparticles for enhanced magnetic tumor targeting. Biomaterials 32(8):2183–2193. doi: 10.1016/j.biomaterials.2010.11.040 CrossRefGoogle Scholar
  11. Cooper GM, Hausman RE (2009) Lysosomes. The cell: a molecular approach, 5th edn. Sinauer Associates, SunderlandGoogle Scholar
  12. Coradin T, Lopez P (2003) Biogenic silica patterning: simple chemistry or subtle biology? ChemBioChem 3:1–9Google Scholar
  13. Creixell M, Herrera AP, Latorre-Esteves M, Ayala V, Torres-Lugo M, Rinaldi C (2010) The effect of grafting method on the colloidal stability and in vitro cytotoxicity of carboxymethyl dextran coated magnetic nanoparticles. J Mater Chem 20(39):8539–8547. doi: 10.1039/c0jm01504k CrossRefGoogle Scholar
  14. Creixell M, Bohorquez AC, Torres-Lugo M, Rinaldi C (2011) EGFR-targeted magnetic nanoparticle heaters kill cancer cells without a perceptible temperature rise. ACS Nano 5(9):7124–7129. doi: 10.1021/nn201822b CrossRefGoogle Scholar
  15. de Chickera SN, Snir J, Willert C, Rohani R, Foley R, Foster PJ, Dekaban GA (2011) Labelling dendritic cells with SPIO has implications for their subsequent in vivo migration as assessed with cellular MRI. Contrast Media Mol Imaging 6(4):314–327. doi: 10.1002/cmmi.433 Google Scholar
  16. De Palma R, Peeters S, Van Bael M, Van den Rul H, Bonroy K, Laureyn W, Mullens J, Borghs G, Maes G (2007) Silane ligand exchange to make hydrophobic superparamagnetic nanoparticles water-dispersible. Chem Mater 19:1821–1831CrossRefGoogle Scholar
  17. Dubiel EA, Kuehn C, Wang R (2012) Vermette P In vitro morphogenesis of PANC-1 cells into islet-like aggregates using RGD-covered dextran derivative surfaces. Colloids Surf B Biointerfaces 89(0):117–125. doi: 10.1016/j.colsurfb.2011.09.003 CrossRefGoogle Scholar
  18. Eyler RW, Klug ED, Diephuis F (1947) Determination of degree of substitution of sodium carboxymethylcellulose. Anal Chem 19(1):24–27CrossRefGoogle Scholar
  19. French RA, Jacobson AR, Kim B, Isley SL, Penn RL, Baveye PC (2009) Influence of ionic strength, pH, and cation valence on aggregation kinetics of titanium dioxide nanoparticles. Environ Sci Technol 43(5):1354–1359. doi: 10.1021/es802628n CrossRefGoogle Scholar
  20. Gautier J, Munnier E, Paillard A, Herve K, Douziech-Eyrolles L, Souce M, Dubois P, Chourpa I (2012) A pharmaceutical study of doxorubicin-loaded PEGylated nanoparticles for magnetic drug targeting. Int J Pharm 423(1):16–25CrossRefGoogle Scholar
  21. Ge Y, Zhang Y, Xia J, Ma M, He S, Nie F, Gu N (2009) Effect of surface charge and agglomerate degree of magnetic iron oxide nanoparticles on KB cellular uptake in vitro. Colloids Surf B 73(2):294–301. doi: 10.1016/j.colsurfb.2009.05.031 CrossRefGoogle Scholar
  22. Georgieva JV, Kalicharan D, Couraud P-O, Romero IA, Weksler B, Hoekstra D, Zuhorn IS (2011) Surface characteristics of nanoparticles determine their intracellular fate in and processing by human blood-brain barrier endothelial cells in vitro. Mol Ther 19(2):318–325. doi: 10.1038/mt.2010.236 Google Scholar
  23. Gratton SEA, Ropp PA, Pohlhaus PD, Luft JC, Madden VJ, Napier ME, DeSimone JM (2008) The effect of particle design on cellular internalization pathways. Proc Natl Acad Sci USA 105(33):11613–11618. doi: 10.1073/pnas.0801763105 CrossRefGoogle Scholar
  24. Grenha A (2012) Chitosan nanoparticles: a survey of preparation methods. J Drug Target 20(4):291–300. doi: 10.3109/1061186X.2011.654121 CrossRefGoogle Scholar
  25. Guarnieri D, Guaccio A, Fusco S, Netti P (2011) Effect of serum proteins on polystyrene nanoparticle uptake and intracellular trafficking in endothelial cells. J Nanopart Res 13(9):4295–4309. doi: 10.1007/s11051-011-0375-2 CrossRefGoogle Scholar
  26. Häfeli UO, Riffle JS, Harris-Shekhawat L, Carmichael-Baranauskas A, Mark F, Dailey JP, Bardenstein D (2009) Cell uptake and in vitro toxicity of magnetic nanoparticles suitable for drug delivery. Mol Pharm 6(5):1417–1428. doi: 10.1021/mp900083m CrossRefGoogle Scholar
  27. Han G-C, Ouyang Y, Long X-Y, Zhou Y, Li M, Liu Y-N, Kraatz H-B (2010) (Carboxymethyl-Dextran)-modified magnetic nanoparticles conjugated to octreotide for MRI applications. Eur J Inorg Chem 34:5455–5461. doi: 10.1002/ejic.201000715 CrossRefGoogle Scholar
  28. Herrera AP, Barrera C, Rinaldi C (2008) Synthesis and functionalization of magnetite nanoparticles with aminopropyl-silane and carboxymethyl-dextran. J Mater Chem 18:3650–3654. doi: 10.1039/B805256E CrossRefGoogle Scholar
  29. Huang J, Zhao R, Wang H, Zhao W, Ding L (2010) Immobilization of glucose oxidase on Fe3O4/SiO2; magnetic nanoparticles. Biotechnol Lett 32(6):817–821. doi: 10.1007/s10529-010-0217-9 CrossRefGoogle Scholar
  30. Huynh F, Jozefonvicz J (1998) Carboxymethylation of dextran in aqueous alcohol as the first step of the preparation of derivatized dextrans. Die Angew Makromol Chem 254:61–65CrossRefGoogle Scholar
  31. Ivanov AI, Nusrat A, Parkos CA (2004) Endocytosis of epithelial apical junctional proteins by a clathrin-mediated pathway into a unique storage compartment. Mol Biol Cell 15(1):176–188. doi: 10.1091/mbc.E03-05-0319 CrossRefGoogle Scholar
  32. Jedlovszky-Hajdú A, Bombelli FB, Monopoli MP, Tombácz E, Dawson KA (2012) Surface coatings shape the protein corona of SPIONs with relevance to their application in vivo. Langmuir 28(42):14983–14991. doi: 10.1021/la302446h CrossRefGoogle Scholar
  33. Jung C (1995) Surface properties of superparamagnetic iron oxide MR contrast agents: ferumoxides, ferumoxtran, ferumoxsil. Magn Reson Imaging 13:675–691CrossRefGoogle Scholar
  34. Jung BS, Lomeli E, Anvari B (2010) Effect of coating material on uptake of indocyanine green-loaded nanocapsules by HeLa cervical cancer cells. In: Jansen ED, Thomas RJ (eds) Optical interactions with tissues and cells XXI. Proc SPIE, vol 7562. doi: 10.1117/12.842754
  35. Jung MJ, Ha YE, Lee DY (2011) Heparin-coated superparamagnetic iron oxide nanoparticles as highly effective MRI contrast agent for cell labeling. J Control Release 152(Suppl 1):e214–e215CrossRefGoogle Scholar
  36. Klostergaard J, Seeney CE (2012) Magnetic nanovectors for drug delivery. Maturitas 73(1):33–44CrossRefGoogle Scholar
  37. Laurent S, Dutz S, Haefeli UO, Mahmoudi M (2011) Magnetic fluid hyperthermia: focus on superparamagnetic iron oxide nanoparticles. Adv Colloid Interface Sci 166(1–2):8–23. doi: 10.1016/j.cis.2011.04.003 Google Scholar
  38. Laurent S, Burtea C, Thirifays C, Häfeli UO, Mahmoudi M (2012) Crucial ignored parameters on nanotoxicology: the importance of toxicity assay modifications and “cell vision”. PLoS One 7(1):e29997. doi: 10.1371/journal.pone.0029997 CrossRefGoogle Scholar
  39. Laurent S, Burtea C, Thirifays C, Rezaee F, Mahmoudi M (2013) Significance of cell “observer” and protein source in nanobiosciences. J Colloid Interface Sci 392(0):431–445. doi: org/10.1016/j.jcis.2012.10.005 CrossRefGoogle Scholar
  40. Li D, Teoh WY, Gooding JJ, Selomulya C, Amal R (2010) Functionalization strategies for protease immobilization on magnetic nanoparticles. Adv Funct Mater 20(11):1767–1777. doi: 10.1002/adfm.201000188 CrossRefGoogle Scholar
  41. Lin-Vien D, Colthup N, Fateley W, Graselli J (1991) The handbook of infrared and Raman characteristic frequencies of organic molecules. Academic Press, San DiegoGoogle Scholar
  42. Mahmoudi M, Saeedi-Eslami SN, Shokrgozar MA, Azadmanesh K, Hassanlou M, Kalhor HR, Burtea C, Rothen-Rutishauser B, Laurent S, Sheibani S, Vali H (2012) Cell “vision”: complementary factor of protein corona in nanotoxicology. Nanoscale 4(17):5461–5468CrossRefGoogle Scholar
  43. Manju S, Sreenivasan K (2011) Enhanced drug loading on magnetic nanoparticles by layer-by-layer assembly using drug conjugates: blood compatibility evaluation and targeted drug delivery in cancer cells. Langmuir 27(23):14489–14496. doi: 10.1021/la202470k CrossRefGoogle Scholar
  44. McMahon HT, Boucrot E (2011) Molecular mechanism and physiological functions of clathrin-mediated endocytosis. Nat Rev Mol Cell Biol 12(8):517–533. doi: 10.1038/nrm3151 Google Scholar
  45. Mikhaylov G, Vasiljeva O (2011) Promising approaches in using magnetic nanoparticles in oncology. Biol Chem 392:955–960. doi: 10.1515/bc.2011.185 CrossRefGoogle Scholar
  46. Miles WC, Goff JD, Huffstetler PP, Reinholz CM, Pothayee N, Caba BL, Boyd JS, Davis RM, Riffle JS (2008) Synthesis and colloidal properties of polyether−magnetite complexes in water and phosphate-buffered saline. Langmuir 25(2):803–813. doi: 10.1021/la8030655 CrossRefGoogle Scholar
  47. Modi S, Swetha MG, Goswami D, Gupta GD, Mayor S, Krishnan Y (2009) A DNA nanomachine that maps spatial and temporal pH changes inside living cells. Nat Nano 4 (5):325–330. doi: 10.1038/nnano.2009.83 Google Scholar
  48. Mornet S, Vasseur S, Grasset F, Duguet E (2004) Magnetic nanoparticle design for medical diagnosis and therapy. J Mater Chem 14:2161–2175CrossRefGoogle Scholar
  49. Mornet S, Portier J, Duguet E (2005) A method for synthesis and functionalization of ultrasmall supeparamagentic covalent carriers based on maghemite and dextran. J Magn Magn Mater 293:127–134CrossRefGoogle Scholar
  50. Navarro-García F, Canizalez-Roman A, Vidal JE, Salazar MI (2007) Intoxication of epithelial cells by plasmid-encoded toxin requires clathrin-mediated endocytosis. Microbiology 153(9):2828–2838. doi: 10.1099/mic.0.2007/007088-0 CrossRefGoogle Scholar
  51. Ning S, Huang Q, Sun X, Li C, Zhang Y, Li J, Liu Y-N (2011) Carboxymethyl dextran-coated liposomes: toward a robust drug delivery platform. Soft Matter 7(19):9394–9401CrossRefGoogle Scholar
  52. Orlandi PA, Fishman PH (1998) Filipin-dependent inhibition of cholera toxin: evidence for toxin internalization and activation through caveolae-like domains. J Cell Biol 141(4):905–915. doi: 10.1083/jcb.141.4.905 CrossRefGoogle Scholar
  53. Osakaa T, Nakanishib T, Shanmugama S, Takahamaa S, Zhangb H (2009) Effect of surface charge of magnetite nanoparticles on their internalization into breast cancer and umbilical vein endothelial cells. Colloids Surf B 71:325–330CrossRefGoogle Scholar
  54. Park K, Hwang Y, Park J, Noh H, Kim J, Hwang N, Hyeon T (2004) Ultra large-scale synthesis of monodisperse nanocrystals. Nat Mater 3:891–895CrossRefGoogle Scholar
  55. Phadatare MR, Khot VM, Salunkhe AB, Thorat ND, Pawar SH (2012) Studies on polyethylene glycol coating on NiFe(2)O(4) nanoparticles for biomedical applications. J Magn Magn Mater 324(5):770–772. doi: 10.1016/j.jmmm.2011.09.020 CrossRefGoogle Scholar
  56. Plueddemann E (1982) Silane coupling agents. Plenum Press, New YorkCrossRefGoogle Scholar
  57. Posner BI, Khan MN, Bergeron JJ (1982) Endocytosis of peptide hormones and other ligands. Endocr Rev 3(3):280–298. doi: 10.1210/edrv-3-3-280 CrossRefGoogle Scholar
  58. 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 311:282–287CrossRefGoogle Scholar
  59. Rauch J, Kolch W, Mahmoudi M (2012) Cell type-specific activation of AKT and ERK signaling pathways by small negatively-charged magnetic nanoparticles. Sci Rep 2:868CrossRefGoogle Scholar
  60. Ravikumar C, Kumar S, Bandyopadhyaya R (2012) Aggregation of dextran coated magnetic nanoparticles in aqueous medium: experiments and Monte Carlo simulation. Colloids Surf A 403:1–6CrossRefGoogle Scholar
  61. Santosh S, Podaralla P, Miller B (2010) Anaphylaxis with elevated serum tryptase after administration of intravenous ferumoxytol. NDT Plus 3(4):341–342. doi: 10.1093/ndtplus/sfq084 CrossRefGoogle Scholar
  62. Schapiro FB, Lingwood C, Furuya W, Grinstein S (1998) pH-independent retrograde targeting of glycolipids to the Golgi complex. A J Physiol Cell Physiol 274(2):C319–C332Google Scholar
  63. Thorek DLJ, Tsourkas A (2008) Size, charge and concentration dependent uptake of iron oxide particles by non-phagocytic cells. Biomaterials 29(26):3583–3590CrossRefGoogle Scholar
  64. Veiseh O, Gunn JW, Zhang M (2010) Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging. Adv Drug Deliv Rev 62(3):284–304. doi: 10.1016/j.addr.2009.11.002 CrossRefGoogle Scholar
  65. Villanueva A, Magdalena C, Alejandro GR, Macarena C, Sabino V-V, Carlos JS, María del Puerto M, Rodolfo M (2009) The influence of surface functionalization on the enhanced internalization of magnetic nanoparticles in cancer cells. Nanotechnology 20(11):115103CrossRefGoogle Scholar
  66. Walczyk D, Bombelli FB, Monopoli MP, Lynch I, Dawson KA (2010) What the cell “sees” in bionanoscience. J Am Chem Soc 132(16):5761–5768. doi: 10.1021/ja910675v CrossRefGoogle Scholar
  67. 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(6):1001–1011. doi: 10.1016/s0142-9612(02)00440-4 CrossRefGoogle Scholar
  68. Wotschadlo J, Liebert T, Heinze T, Wagner K, Schnabelrauch M, Dutz S, Mueller R, Steiniger F, Schwalbe M, Kroll TC, Hoeffken K, Buske N, Clement JH (2009) Magnetic nanoparticles coated with carboxymethylated polysaccharide shells-Interaction with human cells. J Magn Magn Mater 321(10):1469–1473. doi: 10.1016/j.jmmm.2009.02.069 CrossRefGoogle Scholar
  69. Xu H, Aguilar ZP, Yang L, Kuang M, Duan H, Xiong Y, Wei H, Wang A (2011) Antibody conjugated magnetic iron oxide nanoparticles for cancer cell separation in fresh whole blood. Biomaterials 32(36):9758–9765CrossRefGoogle Scholar
  70. Yamaura M, Camilo RL, Sampaio LC, Macedo MA, Nakamura M, Toma HE (2004) Preparation and characterization of (3-aminopropyl) triethoxysilane-coated magnetite nanoparticles. J Magn Magn Mater 279:210–217CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Vanessa Ayala
    • 1
  • Adriana P. Herrera
    • 1
  • Magda Latorre-Esteves
    • 1
  • Madeline Torres-Lugo
    • 1
  • Carlos Rinaldi
    • 1
    • 2
    Email author
  1. 1.Department of Chemical EngineeringUniversity of Puerto RicoMayagüezUSA
  2. 2.J. Crayton Pruitt Family Department of Biomedical EngineeringUniversity of FloridaGainesvilleUSA

Personalised recommendations