Abstract
Superparamagnetic iron oxide (SPIO, Ferumoxides, Feridex), an important MRI intravenous contrast reagent, is efficiently recognized and eliminated by macrophages in the liver, spleen, lymph nodes and atherosclerotic lesions. The receptors that recognize nanoparticles are poorly defined and understood. Since SPIO is coated with bacterial polysaccharide dextran, it is important to know whether carbohydrate recognition plays a role in nanoparticle uptake by macrophages. Lectin-like receptors CD206 (macrophage mannose receptor) and SIGNR1 were previously shown to mediate uptake of bacterial polysaccharides. We transiently expressed receptors MGL-1, SIGNR-1 and msDectin-1 in non-macrophage 293T cells using lipofection. The expression was confirmed by reverse transcription PCR. Following incubation with the nanoparticles, the uptake in receptor-expressing cells was not statistically different compared to control cells (GFP-transfected). At the same time, expression of scavenger receptor SR-A1 increased the uptake of nanoparticles three-fold compared to GFP-transfected and control vector-transfected cells. Blocking CD206 with anti-CD206 antibody or with the ligand mannan did not affect SPIO uptake by J774.A1 macrophages. Similarly, there was no inhibition of the uptake by anti-CD11b (Mac-1 integrin) antibody. Polyanionic scavenger receptor ligands heparin, polyinosinic acid, fucoidan and dextran sulfate decreased the uptake of SPIO by J774A.1 macrophages and Kupffer cells by 60–75%. These data unambiguously show that SPIO is taken up via interaction by scavenger receptors, but not via dextran recognition by carbohydrate receptors. Understanding of nanoparticle-receptor interaction can provide guidance for the design of long circulating, non-toxic nanomedicines.
Ying Chao and Priya Prakash Karmali contributed equally to this chapter.
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References
Berry, C. C., Wells, S., Charles, S., Aitchison, G., & Curtis, A. S. (2004). Cell response to dextran-derivatised iron oxide nanoparticles post internalisation. Biomaterials, 25, 5405–5413.
Cedervall, T., Lynch, I., Lindman, S., Berggard, T., Thulin, E., Nilsson, H., Dawson, K. A., & Linse, S. (2007). Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles. Proceedings of the National Academy of Sciences of the United States of America, 104, 2050–2055.
Chonn, A., Semple, S. C., & Cullis, P. R. (1992). Association of blood proteins with large unilamellar liposomes in vivo. Relation to circulation lifetimes. The Journal of Biological Chemistry, 267, 18759–18765.
Colman, R. W., & Schmaier, A. H. (1997). Contact system: A vascular biology modulator with anticoagulant, profibrinolytic, antiadhesive, and proinflammatory attributes. Blood, 90, 3819–3843.
Demoy, M., Andreux, J. P., Weingarten, C., Gouritin, B., Guilloux, V., & Couvreur, P. (1999). In vitro evaluation of nanoparticles spleen capture. Life Sciences, 64, 1329–1337.
Dobrovolskaia, M. A., & McNeil, S. E. (2007). Immunological properties of engineered nanomaterials. Nature Nanotechnology, 2, 469–478.
Doi, T., Higashino, K., Kurihara, Y., Wada, Y., Miyazaki, T., Nakamura, H., Uesugi, S., Imanishi, T., Kawabe, Y., Itakura, H., et al. (1993). Charged collagen structure mediates the recognition of negatively charged macromolecules by macrophage scavenger receptors. The Journal of Biological Chemistry, 268, 2126–2133.
Jozefowski, S., Arredouani, M., Sulahian, T., & Kobzik, L. (2005). Disparate regulation and function of the class a scavenger receptors SR-AI/II and MARCO. Journal of Immunology, 175, 8032–8041.
Jung, C. W. (1995). Surface properties of superparamagnetic iron oxide MR contrast agents: Ferumoxides, ferumoxtran, ferumoxsil. Magnetic Resonance Imaging, 13, 675–691.
Jung, C. W., & Jacobs, P. (1995). Physical and chemical properties of superparamagnetic iron oxide MR contrast agents: Ferumoxides, ferumoxtran, ferumoxsil. Magnetic Resonance Imaging, 13, 661–674.
Kang, Y. S., Kim, J. Y., Bruening, S. A., Pack, M., Charalambous, A., Pritsker, A., Moran, T. M., Loeffler, J. M., Steinman, R. M., & Park, C. G. (2004). The C-type lectin SIGN-R1 mediates uptake of the capsular polysaccharide of streptococcus pneumoniae in the marginal zone of mouse spleen. Proceedings of the National Academy of Sciences of the United States of America, 101, 215–220.
Kanno, S., Furuyama, A., & Hirano, S. (2007). A murine scavenger receptor MARCO recognizes polystyrene nanoparticles. Toxicological Sciences, 97, 398–406.
Kuroki, Y., Honma, T., Chiba, H., Sano, H., Saitoh, M., Ogasawara, Y., Sohma, H., & Akino, T. (1997). A novel type of binding specificity to phospholipids for rat mannose-binding proteins isolated from serum and liver. FEBS Letters, 414, 387–392.
le Cabec, V., Emorine, L. J., Toesca, I., Cougoule, C., & Maridonneau-Parini, I. (2005). The human macrophage mannose receptor is not a professional phagocytic receptor. Journal of Leukocyte Biology, 77, 934–943.
Lynch, I., Salvati, A., & Dawson, K. A. (2009). Protein-nanoparticle interactions: What does the cell see? Nature Nanotechnology, 4, 546–547.
Moghimi, S. M. (2002). Liposome recognition by resident and newly recruited murine liver macrophages. Journal of Liposome Research, 12, 67–70.
Moghimi, S. M., Hunter, A. C., & Murray, J. C. (2001). Long-circulating and target-specific nanoparticles: Theory to practice. Pharmacological Reviews, 53, 283–318.
Moghimi, S. M., Hamad, I., Andresen, T. L., Jorgensen, K., & Szebeni, J. (2006). Methylation of the phosphate oxygen moiety of phospholipid-methoxy(polyethylene glycol) conjugate prevents PEGylated liposome-mediated complement activation and anaphylatoxin production. The FASEB Journal, 20, 2591–2593.
Nagayama, S., Ogawara, K., Minato, K., Fukuoka, Y., Takakura, Y., Hashida, M., Higaki, K., & Kimura, T. (2007). Fetuin mediates hepatic uptake of negatively charged nanoparticles via scavenger receptor. International Journal of Pharmaceutics, 329, 192–198.
Oberdorster, G., Oberdorster, E., & Oberdorster, J. (2005). Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles. Environmental Health Perspectives, 113, 823–839.
Raynal, I., Prigent, P., Peyramaure, S., Najid, A., Rebuzzi, C., & Corot, C. (2004). Macrophage endocytosis of superparamagnetic iron oxide nanoparticles: Mechanisms and comparison of ferumoxides and ferumoxtran-10. Investigative Radiology, 39, 56–63.
Ross, G. D. (2002). Role of the lectin domain of Mac-1/CR3 (CD11b/CD18) in regulating intercellular adhesion. Immunologic Research, 25, 219–227.
Schousboe, I. (1985). Beta 2-Glycoprotein I: A plasma inhibitor of the contact activation of the intrinsic blood coagulation pathway. Blood, 66, 1086–1091.
Simberg, D., Park, J. H., Karmali, P. P., Zhang, W. M., Merkulov, S., McCrae, K., Bhatia, S. N., Sailor, M., & Ruoslahti, E. (2009). Differential proteomics analysis of the surface heterogeneity of dextran iron oxide nanoparticles and the implications for their in vivo clearance. Biomaterials, 30, 3926–3933.
Tan, S. M., Chung, M. C., Kon, O. L., Thiel, S., Lee, S. H., & Lu, J. (1996). Improvements on the purification of mannan-binding lectin and demonstration of its Ca(2+)-independent association with a C1s-like serine protease. Biochemical Journal, 319(Pt 2), 329–332.
Taylor, P. R., Martinez-Pomares, L., Stacey, M., Lin, H. H., Brown, G. D., & Gordon, S. (2005). Macrophage receptors and immune recognition. Annual Review of Immunology, 23, 901–944.
Von Zur Muhlen, C., Von Elverfeldt, D., Bassler, N., Neudorfer, I., Steitz, B., Petri-Fink, A., Hofmann, H., Bode, C., & Peter, K. (2007). Superparamagnetic iron oxide binding and uptake as imaged by magnetic resonance is mediated by the integrin receptor Mac-1 (CD11b/CD18): implications on imaging of atherosclerotic plaques. Atherosclerosis, 193, 102–11.
Acknowledgements
Authors wish to thank Dr. Erkki Ruoslahti from Sanford-Burnham Medical Research Institute at UCSB for his relentless support and guidance throughout the project. Dr. Yuko Kono from UCSD Department of Radiology is acknowledged for providing Feridex I.V. The work was supported by NIH NCI grants CA119335 and CA124427.
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Chao, Y., Karmali, P.P., Simberg, D. (2012). Role of Carbohydrate Receptors in the Macrophage Uptake of Dextran-Coated Iron Oxide Nanoparticles. In: Zahavy, E., Ordentlich, A., Yitzhaki, S., Shafferman, A. (eds) Nano-Biotechnology for Biomedical and Diagnostic Research. Advances in Experimental Medicine and Biology, vol 733. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2555-3_11
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