Skip to main content
SpringerLink
Log in

Cellular Uptake Mechanisms and Detection of Nanoparticle Uptake by Advanced Imaging Methods

  • Chapter
  • First Online:
Biological Responses to Nanoscale Particles

Part of the book series: NanoScience and Technology ((NANO))

Abstract

The specific mechanism, of uptake of a nanoparticle by a cell and the subcellular localisation are of great importance regarding the potential effect of the nanomaterial inside the cell. In order to study health risks and the potential of a nanoparticle to be used in biomedical applications, cellular internalization has to be investigated in great detail. This chapter highlights most relevant routes of nanoparticle uptake and includes current approaches for the visualization of particle uptake at the nano-level.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Beddoes, C.M., Case, C.P., Briscoe, W.H.: Understanding nanoparticle cellular entry: a physicochemical perspective. Adv. Colloid Interface Sci. 48–68 (2015). https://doi.org/10.1016/j.cis.2015.01.007

  2. Abbas, K., Cydzik, I., Del Torchio, R., Farina, M., Forti, E., Gibson, N., et al.: Radiolabelling of TiO2 nanoparticles for radiotracer studies. J Nanopart. Res. 12, 2435–2443 (2010). https://doi.org/10.1007/s11051-009-9806-8

    Article  Google Scholar 

  3. Maynard, A.D., Aitken, R.J., Butz, T., Colvin, V., Donaldson, K., Oberdörster, G., et al.: Safe handling of nanotechnology. Nature 444, 267–269 (2006). https://doi.org/10.1038/444267a

    Article  ADS  Google Scholar 

  4. Nel, A., Xia, T., Mädler, L., Li, N.: Toxic potential of materials at the nanolevel. Science 622–627 (2006). https://doi.org/10.1126/science.1114397

  5. Service, R.F.: Priorities needed for nano-risk research and development. Science. 45 (2006). https://doi.org/10.1126/science.314.5796.45

  6. Barnard, A.S.: Nanohazards: Knowledge is our first defence. Nat. Mater. 5, 245–248 (2006). https://doi.org/10.1038/nmat1615

    Article  ADS  Google Scholar 

  7. Handy, R.D., Von Der Kammer, F., Lead, J.R., Hassellöv, M., Owen, R., Crane, M.: The ecotoxicology and chemistry of manufactured nanoparticles. Ecotoxicology 287–314 (2008). https://doi.org/10.1007/s10646-008-0199-8

  8. Linse, S., Cabaleiro-Lago, C., Xue, W.-F., Lynch, I., Lindman, S., Thulin, E., et al.: Nucleation of protein fibrillation by nanoparticles. Proc. Natl. Acad. Sci. 104, 8691–8696 (2007). https://doi.org/10.1073/pnas.0701250104

    Article  ADS  Google Scholar 

  9. Lunov, O., Zablotskii, V., Syrovets, T., Röcker, C., Tron, K., Nienhaus, G.U., et al.: Modeling receptor-mediated endocytosis of polymer-functionalized iron oxide nanoparticles by human macrophages. Biomaterials 32, 547–555 (2011). https://doi.org/10.1016/j.biomaterials.2010.08.111

    Article  Google Scholar 

  10. Lunov, O., Syrovets, T., Röcker, C., Tron, K., Ulrich Nienhaus, G., Rasche, V., et al.: Lysosomal degradation of the carboxydextran shell of coated superparamagnetic iron oxide nanoparticles and the fate of professional phagocytes. Biomaterials 31, 9015–9022 (2010). https://doi.org/10.1016/j.biomaterials.2010.08.003

    Article  Google Scholar 

  11. Yameen, B., Choi, W.I., Vilos, C., Swami, A., Shi, J., Farokhzad, O.C.: Insight into nanoparticle cellular uptake and intracellular targeting. J Control Release. 190, 485–499 (2014). https://doi.org/10.1016/j.jconrel.2014.06.038

    Article  Google Scholar 

  12. Treuel, L., Jiang, X., Nienhaus, G.U.: New views on cellular uptake and trafficking of manufactured nanoparticles. J. R. Soc. Interface 10, 20120939–20120939 (2013). https://doi.org/10.1098/rsif.2012.0939

    Article  Google Scholar 

  13. AshaRani, P.V., Mun, G.L.K., Hande, M.P., Valiyaveettil, S.: Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano 3, 279–290 (2009). https://doi.org/10.1021/nn800596w

    Article  Google Scholar 

  14. Chithrani, B.D., Ghazani, A.A., Chan, W.C.W.: Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett. 6, 662–668 (2006). https://doi.org/10.1021/nl052396o

    Article  ADS  Google Scholar 

  15. Rejman, J., Oberle, V., Zuhorn, I.S., Hoekstra, D.: Size-dependent internalization of particles via the pathways of clathrin- and caveolae-mediated endocytosis. Biochem J. 377, 159–169 (2004). https://doi.org/10.1042/bj20031253

  16. Labhasetwar, V., Song, C., Humphrey, W., Shebuski, R., Levy, R.J.: Arterial uptake of biodegradable nanoparticles: effect of surface modifications. J. Pharm. Sci. 87, 1229–1234 (1998). https://doi.org/10.1021/js980021f

    Article  Google Scholar 

  17. Arbab, A.S., Bashaw, L.A., Miller, B.R., Jordan, E.K., Lewis, B.K., Kalish, H., et al.: Characterization of biophysical and metabolic properties of cells labeled with superparamagnetic iron oxide nanoparticles and transfection agent for cellular MR imaging. Radiology 229, 838–846 (2003). https://doi.org/10.1148/radiol.2293021215

    Article  Google Scholar 

  18. Sun, X., Rossin, R., Turner, J.L., Becker, M.L., Joralemon, M.J., Welch, M.J., et al.: An assessment of the effects of shell cross-linked nanoparticle size, core composition, and surface PEGylation on in vivo biodistribution. Biomacromolecules 6, 2541–2554 (2005). https://doi.org/10.1021/bm050260e

    Article  Google Scholar 

  19. Nativo, P., Prior, I.A., Brust, M.: Uptake and intracellular fate of surface-modified gold nanoparticles. ACS Nano 2, 1639–1644 (2008). https://doi.org/10.1021/nn800330a

    Article  Google Scholar 

  20. Holzapfel, V., Lorenz, M., Weiss, C.K., Schrezenmeier, H., Landfester, K., Mailänder, V.: Synthesis and biomedical applications of functionalized fluorescent and magnetic dual reporter nanoparticles as obtained in the miniemulsion process. J. Phys. Condens. Matter. 18 (2006). https://doi.org/10.1088/0953-8984/18/38/s04

  21. Rajendran, L., Knölker, H.-J., Simons, K.: Subcellular targeting strategies for drug design and delivery. Nat. Rev. Drug Discov. 9, 29–42 (2010). https://doi.org/10.1038/nrd2897

    Article  Google Scholar 

  22. Huang, J.G., Leshuk, T., Gu, F.X.: Emerging nanomaterials for targeting subcellular organelles. Nano Today 478–492 (2011). https://doi.org/10.1016/j.nantod.2011.08.002

  23. Kettiger, H., Schipanski, A., Wick, P., Huwyler, J.: Engineered nanomaterial uptake and tissue distribution: from cell to organism. Int. J. Nanomed. 3255–3269 (2013). https://doi.org/10.2147/ijn.s49770

  24. Aderem, A., Underhill, D.M.: Mechanisms of phagocytosis in macrophages. Annu. Rev. Immunol. 17, 593–623 (1999). https://doi.org/10.1146/annurev.immunol.17.1.593

    Article  Google Scholar 

  25. Hillaireau, H., Couvreur, P.: Nanocarriers’ entry into the cell: relevance to drug delivery. Cell. Mol. Life Sci. 66, 2873–2896 (2009). https://doi.org/10.1007/s00018-009-0053-z

    Article  Google Scholar 

  26. Silverstein, S.C.: Phagocytosis of microbes: insights and prospects. Trends Cell Biol. 5, 141–142 (1995). https://doi.org/10.1016/S0962-8924(00)88967-9

    Article  Google Scholar 

  27. Owens, D.E., Peppas, N.A.: Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int. J. Pharm. 93–102 (2006). https://doi.org/10.1016/j.ijpharm.2005.10.010

  28. Underhill, D.M., Goodridge, H.S.: Information processing during phagocytosis. Nat. Rev. Immunol. 492–502 (2012). https://doi.org/10.1038/nri3244

  29. Rabinovitch, M.: Professional and non-professional phagocytes: an introduction. Trends Cell Biol. 5, 85–87 (1995). https://doi.org/10.1016/S0962-8924(00)88955-2

    Article  Google Scholar 

  30. Dobrovolskaia, M.A., Mcneil, S.E.: Immunological properties of engineered nanomaterials. Nat. Nanotechnol. 2, 469–478 (2007)

    ADS  Google Scholar 

  31. Conner, S.D., Schmid, S.L.: Regulated portals of entry into the cell. Nature. 422, 37–44 (2003). https://doi.org/10.1038/nature01451

  32. Falcone, S., Cocucci, E., Podini, P., Kirchhausen, T., Clementi, E., Meldolesi, J.: Macropinocytosis: regulated coordination of endocytic and exocytic membrane traffic events. J. Cell Sci. 119, 4758–4769 (2006). https://doi.org/10.1242/jcs.03238

    Article  Google Scholar 

  33. Mercer, J., Helenius, A.: Virus entry by macropinocytosis. Nat. Cell Biol. 510–520 (2009). https://doi.org/10.1038/ncb0509-510

  34. Kolb-Mäurer, A., Wilhelm, M., Weissinger, F., Bröcker, E.-B., Goebel, W.: Interaction of human hematopoietic stem cells with bacterial pathogens. Blood 100, 3703–3709 (2002). https://doi.org/10.1182/blood-2002-03-0898

    Article  Google Scholar 

  35. Fiorentini, C., Falzano, L., Fabbri, A., Stringaro, A., Logozzi, M., Travaglione, S., et al.: Activation of rho GTPases by cytotoxic necrotizing factor 1 induces macropinocytosis and scavenging activity in epithelial cells. Mol. Biol. Cell 12, 2061–2073 (2001). https://doi.org/10.1091/mbc.12.7.2061

    Article  Google Scholar 

  36. Steinman, R.M., Swanson, J.: The endocytic activity of dendritic cells. J Exp Med. United States 182, 283–288 (1995)

    Google Scholar 

  37. Sallusto, F., Cella, M., Danieli, C., Lanzavecchia, A.: Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products. J. Exp. Med. 182, 389–400 (1995). https://doi.org/10.1084/jem.182.2.389

  38. Kerr, M.C., Teasdale, R.D.: Defining macropinocytosis. Traffic 364–371 (2009). https://doi.org/10.1111/j.1600-0854.2009.00878.x

  39. Rima, W., Sancey, L., Aloy, M.T., Armandy, E., Alcantara, G.B., Epicier, T., et al.: Internalization pathways into cancer cells of gadolinium-based radiosensitizing nanoparticles. Biomaterials 34, 181–195 (2013). https://doi.org/10.1016/j.biomaterials.2012.09.029

    Article  Google Scholar 

  40. Kumari, S., Mg, S., Mayor, S.: Endocytosis unplugged: multiple ways to enter the cell. Cell Res. 256–275 (2010). https://doi.org/10.1038/cr.2010.19

  41. Kirchhausen, T.: Clathrin. Annu. Rev. Biochem. 69, 699–727 (2000). https://doi.org/10.1146/annurev.biochem.69.1.699

    Article  Google Scholar 

  42. Sandvig, K., Pust, S., Skotland, T., van Deurs, B.: Clathrin-independent endocytosis: mechanisms and function. Curr. Opin. Cell Biol. 413–420 (2011). https://doi.org/10.1016/j.ceb.2011.03.007

  43. Ford, M.G.J., Mills, I.G., Peter, B.J., Vallis, Y., Praefcke, G.J.K., Evans, P.R., et al.: Curvature of clathrin-coated pits driven by epsin. Nature 419, 361–366 (2002). https://doi.org/10.1038/nature01020

    Article  ADS  Google Scholar 

  44. Capraro, B.R., Shi, Z., Wu, T., Chen, Z., Dunn, J.M., Rhoades, E., et al.: Kinetics of endophilin N-BAR domain dimerization and membrane interactions. J. Biol. Chem. 288, 12533–12543 (2013). https://doi.org/10.1074/jbc.M112.435511

    Article  Google Scholar 

  45. Tebar, F., Bohlander, S.K., Sorkin, A.: Clathrin assembly lymphoid myeloid leukemia (CALM) protein: localization in endocytic-coated pits, interactions with clathrin, and the impact of overexpression on clathrin-mediated traffic. Mol. Biol. Cell 10, 2687–2702 (1999). https://doi.org/10.1091/mbc.10.8.2687

    Article  Google Scholar 

  46. Marsh, M., McMahon, H.T.: The structural era of endocytosis. Science 215–220 (1999). https://doi.org/10.1126/science.285.5425.215

  47. Stowell, M.H., Marks, B., Wigge, P., McMahon, H.T.: Nucleotide-dependent conformational changes in dynamin: evidence for a mechanochemical molecular spring. Nat. Cell Biol. 1, 27–32 (1999). https://doi.org/10.1038/8997

    Article  Google Scholar 

  48. Harush-Frenkel, O., Rozentur, E., Benita, S., Altschuler, Y.: Surface charge of nanoparticles determines their endocytic and transcytotic pathway in polarized MDCK cells. Biomacromol 9, 435–443 (2008). https://doi.org/10.1021/bm700535p

    Article  Google Scholar 

  49. Oh, P., Borgström, P., Witkiewicz, H., Li, Y., Borgström, B.J., Chrastina, A., et al.: Live dynamic imaging of caveolae pumping targeted antibody rapidly and specifically across endothelium in the lung. Nat. Biotechnol. 25, 327–337 (2007). https://doi.org/10.1038/nbt1292

    Article  Google Scholar 

  50. Wang, Z., Tiruppathi, C., Minshall, R.D., Malik, A.B.: Size and dynamics of caveolae studied using nanoparticles in living endothelial cells. ACS Nano 3, 4110–4116 (2009). https://doi.org/10.1021/nn9012274

    Article  Google Scholar 

  51. Hommelgaard, A.M., Roepstorff, K., Vilhardt, F., Torgersen, M.L., Sandvig, K., van Deurs, B.: Caveolae: stable membrane domains with a potential for internalization. Traffic 720–724 (2005). https://doi.org/10.1111/j.1600-0854.2005.00314.x

  52. Howes, M.T., Kirkham, M., Riches, J., Cortese, K., Walser, P.J., Simpson, F., et al.: Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells. J. Cell Biol. 190, 675–691 (2010). https://doi.org/10.1083/jcb.201002119

    Article  Google Scholar 

  53. Parton, R.G., Simons, K.: The multiple faces of caveolae. Nat. Rev. Mol. Cell Biol. 185–194 (2007). https://doi.org/10.1038/nrm2122

  54. Pelkmans, L., Püntener, D., Helenius, A.: Local actin polymerization and dynamin recruitment in SV40-induced internalization of caveolae. Science (80-) 296, 535–539 (2002). https://doi.org/10.1126/science.1069784

  55. Hayer, A., Stoeber, M., Ritz, D., Engel, S., Meyer, H.H., Helenius, A.: Caveolin-1 is ubiquitinated and targeted to intralumenal vesicles in endolysosomes for degradation. J. Cell Biol. 191, 615–629 (2010). https://doi.org/10.1083/jcb.201003086

    Article  Google Scholar 

  56. Parton, R.G., Howes, M.T.: Revisiting caveolin trafficking: the end of the caveosome. J. Cell Biol. 439–441 (2010). https://doi.org/10.1083/jcb.201009093

  57. Gratton, S.E.A., Ropp, P.A., Pohlhaus, P.D., Luft, J.C., Madden, V.J., Napier, M.E., et al.: The effect of particle design on cellular internalization pathways. Proc. Natl. Acad. Sci. 105, 11613–11618 (2008). https://doi.org/10.1073/pnas.0801763105

    Article  ADS  Google Scholar 

  58. Sandvig, K., Torgersen, M.L., Raa, H.A., Van Deurs, B.: Clathrin-independent endocytosis: from nonexisting to an extreme degree of complexity. Histochem. Cell Biol. 267–276 (2008). https://doi.org/10.1007/s00418-007-0376-5

  59. Robertson, A.S., Smythe, E., Ayscough, K.R.: Functions of actin in endocytosis. Cellu. Mol. Life Sci. 2049–2065 (2009). https://doi.org/10.1007/s00018-009-0001-y

  60. Rothen-Rutishauser, B., Mühlfeld, C., Blank, F., Musso, C., Gehr, P.: Translocation of particles and inflammatory responses after exposure to fine particles and nanoparticles in an epithelial airway model. Part Fibre Toxicol. 4 (2007). https://doi.org/10.1186/1743-8977-4-9

  61. Rothen-Rutishauser, B., Schurch, S., Gehr, P.: Interaction of particles with membranes. In: Donaldson, K., Borm, P. (eds.) Particle Toxicology, pp. 139–160. CRC Press, Tyler & Francis Group, Boca Raton, FL (2007)

    Google Scholar 

  62. Xu, S., Olenyuk, B.Z., Okamoto, C.T., Hamm-Alvarez, S.F.: Targeting receptor-mediated endocytotic pathways with nanoparticles: rationale and advances. Adv. Drug Deliv. Rev. 65, 121–138 (2013). https://doi.org/10.1016/j.addr.2012.09.041

    Article  Google Scholar 

  63. Low, P.S., Kularatne, S.A.: Folate-targeted therapeutic and imaging agents for cancer. Curr. Opin. Chem. Biol. 13, 256–262 (2009). https://doi.org/10.1016/j.cbpa.2009.03.022

    Article  Google Scholar 

  64. Muller, C., Schibli, R.: Prospects in folate receptor-targeted radionuclide therapy. Front Oncol. 3, 249 (2013). https://doi.org/10.3389/fonc.2013.00249

    Article  Google Scholar 

  65. Xia, W., Hilgenbrink, A.R., Matteson, E.L., Lockwood, M.B., Cheng, J.X., Low, P.S.: A functional folate receptor is induced during macrophage activation and can be used to target drugs to activated macrophages. Blood 113, 438–446 (2009). https://doi.org/10.1182/blood-2008-04-150789

    Article  Google Scholar 

  66. Ross, J.F., Wang, H., Behm, F.G., Mathew, P., Wu, M., Booth, R., et al.: Folate receptor type beta is a neutrophilic lineage marker and is differentially expressed in myeloid leukemia. Cancer 85, 348–357 (1999). http://www.ncbi.nlm.nih.gov/pubmed/10023702

  67. Low, P.S., Henne, W.A., Doorneweerd, D.D.: Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases. Acc. Chem. Res. 41, 120–129 (2008). https://doi.org/10.1021/ar7000815

    Article  Google Scholar 

  68. Zhao, X., Li, H., Lee, R.J.: Targeted drug delivery via folate receptors. Expert Opin. Drug Deliv. 5, 309–319 (2008). https://doi.org/10.1517/17425247.5.3.309

    Article  Google Scholar 

  69. Werner, M.E., Karve, S., Sukumar, R., Cummings, N.D., Copp, J.A., Chen, R.C., et al.: Folate-targeted nanoparticle delivery of chemo- and radiotherapeutics for the treatment of ovarian cancer peritoneal metastasis. Biomaterials 32, 8548–8554 (2011). https://doi.org/10.1016/j.biomaterials.2011.07.067

    Article  Google Scholar 

  70. Ponka, P., Lok, C.N.: The transferrin receptor: role in health and disease. Int. J. Biochem. Cell. Biol. 31, 1111–1137 (1999). http://www.ncbi.nlm.nih.gov/pubmed/10582342

  71. Sadat Tabatabaei Mirakabad, F., Nejati-Koshki, K., Akbarzadeh, A., Yamchi, M.R., Milani, M., Zarghami, N., et al.: PLGA-based nanoparticles as cancer drug delivery systems. Asian Pac. J. Cancer Prev. 15, 517–535 (2014)

    Google Scholar 

  72. Danhier, F., Feron, O., Preat, V.: To exploit the tumor microenvironment: passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J. Control Release 148, 135–146 (2010). https://doi.org/10.1016/j.jconrel.2010.08.027

    Article  Google Scholar 

  73. van der Meel, R., Vehmeijer, L.J., Kok, R.J., Storm, G., van Gaal, E.V.: Ligand-targeted particulate nanomedicines undergoing clinical evaluation: current status. Adv. Drug Deliv. Rev. 65, 1284–1298 (2013). https://doi.org/10.1016/j.addr.2013.08.012

    Article  Google Scholar 

  74. Mirghani, H., Amen, F., Moreau, F., Guigay, J., Hartl, D.M., Lacau St Guily, J.: Oropharyngeal cancers: relationship between epidermal growth factor receptor alterations and human papillomavirus status. Eur. J. Cancer 50, 1100–1111 (2014). https://doi.org/10.1016/j.ejca.2013.12.018

  75. Holbro, T., Civenni, G., Hynes, N.E.: The ErbB receptors and their role in cancer progression. Exp. Cell Res. 284, 99–110 (2003). http://www.ncbi.nlm.nih.gov/pubmed/12648469

  76. Lurje, G., Lenz, H.J.: EGFR signaling and drug discovery. Oncology 77, 400–410 (2009). https://doi.org/10.1159/000279388

    Article  Google Scholar 

  77. Harris, R.C., Chung, E., Coffey, R.J.: EGF receptor ligands. Exp. Cell Res. 284, 2–13 (2003). http://www.ncbi.nlm.nih.gov/pubmed/12648462

  78. Tseng, C.L., Su, W.Y., Yen, K.C., Yang, K.C., Lin, F.H.: The use of biotinylated-EGF-modified gelatin nanoparticle carrier to enhance cisplatin accumulation in cancerous lungs via inhalation. Biomaterials 30, 3476–3485 (2009). https://doi.org/10.1016/j.biomaterials.2009.03.010

    Article  Google Scholar 

  79. Rajasekaran, A.K., Anilkumar, G., Christiansen, J.J.: Is prostate-specific membrane antigen a multifunctional protein? Am. J. Physiol. Cell Physiol. 288, C975–C981 (2005). https://doi.org/10.1152/ajpcell.00506.2004

    Article  Google Scholar 

  80. Schulke, N., Varlamova, O.A., Donovan, G.P., Ma, D., Gardner, J.P., Morrissey, D.M., et al.: The homodimer of prostate-specific membrane antigen is a functional target for cancer therapy. Proc. Natl. Acad. Sci. U.S.A. 100, 12590–12595 (2003). https://doi.org/10.1073/pnas.1735443100

    Article  ADS  Google Scholar 

  81. Hrkach, J., Von Hoff, D., Mukkaram Ali, M., Andrianova, E., Auer, J., Campbell, T., et al.: Preclinical development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile. Sci. Trans. Med. 4, 128ra39 (2012). https://doi.org/10.1126/scitranslmed.3003651

  82. Tucker, G.C.: Integrins: molecular targets in cancer therapy. Curr. Oncol. Rep. 8, 96–103 (2006). http://www.ncbi.nlm.nih.gov/pubmed/16507218

  83. Gottschalk, K.E., Kessler, H.: The structures of integrins and integrin-ligand complexes: implications for drug design and signal transduction. Angew. Chem. Int. Ed. Engl. 41, 3767–3774 (2002). https://doi.org/10.1002/1521-3773(20021018)41:20%3c3767:AID-ANIE3767%3e3.0.CO;2-T

    Article  Google Scholar 

  84. Eliceiri, B.P., Cheresh, D.A.: Role of alpha v integrins during angiogenesis. Cancer J. 6(Suppl 3), S245–9 (2000). http://www.ncbi.nlm.nih.gov/pubmed/10874494

  85. Brooks, P.C., Stromblad, S., Sanders, L.C., von Schalscha, T.L., Aimes, R.T., Stetler-Stevenson, W.G., et al.: Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alphavbeta3. Cell 85, 683–693 (1996). http://www.ncbi.nlm.nih.gov/pubmed/8646777

  86. Liu, S.: Radiolabeled cyclic RGD peptides as integrin alpha(v)beta(3)-targeted radiotracers: maximizing binding affinity via bivalency. Bioconjug. Chem. 20, 2199–2213 (2009). https://doi.org/10.1021/bc900167c

    Article  Google Scholar 

  87. Auzzas, L., Zanardi, F., Battistini, L., Burreddu, P., Carta, P., Rassu, G., et al.: Targeting alphavbeta3 integrin: design and applications of mono- and multifunctional RGD-based peptides and semipeptides. Curr. Med. Chem. 17, 1255–1299 (2010). http://www.ncbi.nlm.nih.gov/pubmed/20166941

  88. Graf, N., Bielenberg, D.R., Kolishetti, N., Muus, C., Banyard, J., Farokhzad, O.C., et al.: alpha(V)beta(3) integrin-targeted PLGA-PEG nanoparticles for enhanced anti-tumor efficacy of a Pt(IV) prodrug. ACS Nano 6, 4530–4539 (2012). https://doi.org/10.1021/nn301148e

    Article  Google Scholar 

  89. Brambell, F.W.: The transmission of immune globulins from the mother to the foetal and newborn young. Proc. Nutr. Soc. 28, 35–41 (1969). http://www.ncbi.nlm.nih.gov/pubmed/4182340

  90. Pridgen, E.M., Alexis, F., Kuo, T.T., Levy-Nissenbaum, E., Karnik, R., Blumberg, R.S., et al.: Transepithelial transport of Fc-targeted nanoparticles by the neonatal fc receptor for oral delivery. Sci. Transl. Med. 5, 213ra167 (2013). https://doi.org/10.1126/scitranslmed.3007049

  91. Goldberg, M., Gomez-Orellana, I.: Challenges for the oral delivery of macromolecules. Nat. Rev. Drug Discov. 2, 289–295 (2003). https://doi.org/10.1038/nrd1067

    Article  Google Scholar 

  92. Borner, M.M., Schoffski, P., de Wit, R., Caponigro, F., Comella, G., Sulkes, A., et al.: Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial in advanced colorectal cancer. Eur. J. Cancer 38, 349–358 (2002). http://www.ncbi.nlm.nih.gov/pubmed/11818199

  93. Priem, B., Tian, C., Tang, J., Zhao, Y., Mulder, W.J.: Fluorescent nanoparticles for the accurate detection of drug delivery. Expert Opin. Drug Deliv. 12, 1881–1894 (2015). https://doi.org/10.1517/17425247.2015.1074567

    Article  Google Scholar 

  94. Wei, Q., Qi, H., Luo, W., Tseng, D., Ki, S.J., Wan, Z., et al.: Fluorescent imaging of single nanoparticles and viruses on a smart phone. ACS Nano 7, 9147–9155 (2013). https://doi.org/10.1021/nn4037706

    Article  Google Scholar 

  95. Jin, S., Hu, Y., Gu, Z., Liu, L., Wu, H.-C.: Application of quantum dots in biological imaging. J. Nanomater. 2011, 1–13 (2011). https://doi.org/10.1155/2011/834139

    Article  Google Scholar 

  96. He, X., Ma, N.: An overview of recent advances in quantum dots for biomedical applications. Coll. Surf. B Biointerfaces 124, 118–131 (2014). https://doi.org/10.1016/j.colsurfb.2014.06.002

    Article  Google Scholar 

  97. Michalet, X., Pinaud, F.F., Bentolila, L.A., Tsay, J.M., Doose, S., Li, J.J., et al.: Quantum dots for live cells, in vivo imaging, and diagnostics. Science 307, 538–544 (2005). https://doi.org/10.1126/science.1104274

    Article  ADS  Google Scholar 

  98. Bagalkot, V., Zhang, L., Levy-Nissenbaum, E., Jon, S., Kantoff, P.W., Langery, R., et al.: Quantum dot-aptamer conjugates for synchronous cancer imaging, therapy, and sensing of drug delivery based on Bi-fluorescence resonance energy transfer. Nano Lett. 7, 3065–3070 (2007). https://doi.org/10.1021/nl071546n

    Article  ADS  Google Scholar 

  99. Fontes, A., de Lira, R.B., Seabra, M.A.B.L., da Silva, T.G., Castro Neto, A.G., Santos, B.S.: Quantum dots in biomedical research, biomedical engineering—technical applications in medicine [Internet]. In: Hudak, R. (ed.) InTech. https://www.intechopen.com/books/biomedical-engineering-technical-applications-in-medicine/quantum-dots-in-biomedical-research (2012)

  100. England, C.G., Huang, J.S., James, K.T., Zhang, G., Gobin, A., Frieboes, H.B.: Detection of phosphatidylcholine-coated gold nanoparticles in orthotopic pancreatic adenocarcinoma using hyperspectral imaging. PLoS One 10 (2015). https://doi.org/10.1371/journal.pone.0129172

  101. Guggenheim, E.J., Khan, A., Pike, J., Chang, L., Lynch, I., Rappoport JZ. Comparison of confocal and super-resolution reflectance imaging of metal oxide nanoparticles. PLoS One 11 (2016). https://doi.org/10.1371/journal.pone.0159980

  102. Repenko, T., Rix, A., Ludwanowski, S., Go, D., Kiessling, F., Lederle, W., et al.: Bio-degradable highly fluorescent conjugated polymer nanoparticles for bio-medical imaging applications. Nat. Commun. 8 (2017). https://doi.org/10.1038/s41467-017-00545-0

  103. Wolfbeis, O.S.: An overview of nanoparticles commonly used in fluorescent bioimaging. Chem. Soc. Rev. 44, 4743–4768 (2015). https://doi.org/10.1039/C4CS00392F

    Article  Google Scholar 

  104. Chen, X., Cui, J., Sun, H., Mullner, M., Yan, Y., Noi, K.F., et al.: Analysing intracellular deformation of polymer capsules using structured illumination microscopy. Nanoscale 8, 11924–11931 (2016). https://doi.org/10.1039/c6nr02151d

    Article  ADS  Google Scholar 

  105. Fytianos, K., Rodriguez-Lorenzo, L., Clift, M.J.D., Blank, F., Vanhecke, D., von Garnier, C., et al.: Uptake efficiency of surface modified gold nanoparticles does not correlate with functional changes and cytokine secretion in human dendritic cells in vitro. Nanomed. Nanotechnol. Biol. Med. 11 (2015). https://doi.org/10.1016/j.nano.2014.11.004

  106. Lehmann, A.D., Parak, W.J., Zhang, F., Ali, Z., Röcker, C., Nienhaus, G.U., et al.: Fluorescent-magnetic hybrid nanoparticles induce a dose-dependent increase in proinflammatory response in lung cells in vitro correlated with intracellular localization. Small 6, 753–762 (2010)

    Google Scholar 

  107. Blom, R.A.M., Amacker, M., Moser, C., van Dijk, R.M., Bonetti, R., Seydoux, E., et al.: Virosome-bound antigen enhances DC-dependent specific CD4+T cell stimulation, inducing a Th1 and Treg profile in vitro. Nanomed. Nanotechnol. Biol. Med. 13 (2017). https://doi.org/10.1016/j.nano.2017.02.004

  108. Seydoux, E., Rothen-Rutishauser, B., Nita, I.M., Balog, S., Gazdhar, A., Stumbles, P.A., et al.: Size-dependent accumulation of particles in lysosomes modulates dendritic cell function through impaired antigen degradation. Int. J. Nanomed. 9 (2014). https://doi.org/10.2147/ijn.s64353

  109. Hemmerich, P.H., von Mikecz, A.H.: Defining the subcellular interface of nanoparticles by live-cell imaging. PLoS One 8 (2013). https://doi.org/10.1371/journal.pone.0062018

  110. De Los, S.C., Chang, C.-W., Mycek, M.-A., Cardullo, R.A.: FRAP, FLIM, and FRET: detection and analysis of cellular dynamics on a molecular scale using fluorescence microscopy. Mol. Reprod. Dev. 82, 587–604 (2015). https://doi.org/10.1002/mrd.22501

    Article  Google Scholar 

  111. Basuki, J.S., Duong, H.T.T., Macmillan, A., Erlich, R.B., Esser, L., Akerfeldt, M.C., et al.: Using fluorescence lifetime imaging microscopy to monitor theranostic nanoparticle uptake and intracellular doxorubicin release. ACS Nano 7, 10175–10189 (2013). https://doi.org/10.1021/nn404407g

    Article  Google Scholar 

  112. Welsher, K., Yang, H.: Multi-resolution 3D visualization of the early stages of cellular uptake of peptide-coated nanoparticles. Nat. Nanotechnol. 9, 198–203 (2014). https://doi.org/10.1038/nnano.2014.12

    Article  ADS  Google Scholar 

  113. Van Der Zwaag, D., Vanparijs, N., Wijnands, S., De Rycke, R., De Geest, B.G., Albertazzi, L.: Super resolution imaging of nanoparticles cellular uptake and trafficking. ACS Appl. Mater. Interfaces 8, 6391–6399 (2016). https://doi.org/10.1021/acsami.6b00811

    Article  Google Scholar 

  114. Bon, P., Bourg, N., Lécart, S., Monneret, S., Fort, E., Wenger, J., et al.: Three-dimensional nanometre localization of nanoparticles to enhance super-resolution microscopy. Nat. Commun. 6 (2015). https://doi.org/10.1038/ncomms8764

  115. Peuschel, H., Ruckelshausen, T., Cavelius, C., Kraegeloh, A.: Quantification of internalized silica nanoparticles via STED microscopy. Biomed. Res. Int. 2015 (2015). https://doi.org/10.1155/2015/961208

  116. Rodriguez-Lorenzo, L., Fytianos, K., Blank, F., Von Garnier, C., Rothen-Rutishauser, B., Petri-Fink, A.: Fluorescence-encoded gold nanoparticles: library design and modulation of cellular uptake into dendritic cells. Small 10, 1341–1350 (2014). https://doi.org/10.1002/smll.201302889

    Article  Google Scholar 

  117. Clift, M.J.D., Fytianos, K., Vanhecke, D., Hočevar, S., Petri-Fink, A., Rothen-Rutishauser, B.: A novel technique to determine the cell type specific response within an in vitro co-culture model via multi-colour flow cytometry. Sci. Rep. 7, 434 (2017). https://doi.org/10.1038/s41598-017-00369-4

    Article  ADS  Google Scholar 

  118. Mills, N., Rnqvist, H.T., Gonzalez, M., Vink, E., Robinson, S., Soderberg, S., et al.: Ischaemic and thrombotic effects of dilute diesel exhaust inhalation in patients with coronary heart disease: mechanisms for the adverse cardiovascular effects of air pollution. Heart 93, A9–A9 (2007)

    Google Scholar 

  119. Clark, R.T.: Imaging flow cytometry enhances particle detection sensitivity for extracellular vesicle analysis. Nat. Methods. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved; 12 (2015). http://dx.doi.org/10.1038/nmeth.f.380

  120. Vanhecke, D., Rodriguez-Lorenzo, L., Clift, M.J.D., Blank, F., Petri-Fink, A., Rothen-Rutishauser, B.: Quantification of nanoparticles at the single-cell level: an overview about state-of-the-art techniques and their limitations. Nanomedicine 9 (2014). https://doi.org/10.2217/nnm.14.108

Download references

Author information

Authors and Affiliations

  1. Respiratory Medicine, Department of BioMedical Research (DBMR), University of Bern, Murtenstrasse 50, 3008, Bern, Switzerland

    Kleanthis Fytianos & Fabian Blank

  2. University Children’s Hospital Basel, Spitalstrasse 33, 4056, Basel, Switzerland

    Loretta Müller

  3. Department of Pediatrics, Inselspital, Bern University Hospital, Freiburgstrasse 18, 3010, Bern, Switzerland

    Loretta Müller

Authors
  1. Kleanthis Fytianos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fabian Blank
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Loretta Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fabian Blank .

Editor information

Editors and Affiliations

  1. Institute of Anatomy, University of Bern, Bern, Switzerland

    Peter Gehr

  2. Institute of Physical Chemistry, University of Duisburg-Essen, Essen, Germany

    Reinhard Zellner

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Fytianos, K., Blank, F., Müller, L. (2019). Cellular Uptake Mechanisms and Detection of Nanoparticle Uptake by Advanced Imaging Methods. In: Gehr, P., Zellner, R. (eds) Biological Responses to Nanoscale Particles. NanoScience and Technology. Springer, Cham. https://doi.org/10.1007/978-3-030-12461-8_8

Download citation

Publish with us

Policies and ethics

Search

Navigation