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Uptake and Intracellular Trafficking of Nanocarriers

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Intracellular Delivery II

Part of the book series: Fundamental Biomedical Technologies ((FBMT,volume 7))

Abstract

Nanocarriers are widely used for delivery of therapeutic and modulatory agents to eukaryotic cells and specific intracellular compartments. Nanocarrier internalization proceeds via different routes and predominantly via clathrin-coated pits, lipid rafts/caveolae endocytosis and macropinocytosis/phagocytosis, depending on the cell type as well as the physicochemical properties of the nanocarrier. The intracellular fate of the nanocarrier is not only dependent on the mode of entry, but may also be modulated by prior surface modification of nanocarriers with organelle-specific localization ligands. This chapter discusses important methodological aspects for studying cellular uptake and intracellular trafficking of nanocarriers.

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Abbreviations

CME:

Clathrin-mediated endocytosis

ER:

Endoplasmic reticulum

GFP:

Green fluorescence protein

MOC:

Manders overlap coefficient

PALM:

Photoactivated localization microscopy

PCC:

Pearson co-localization coefficient

PEI:

Polyethylenimine

STORM:

Stochastic optical reconstruction microscopy

TEM:

Transmission electron microscopy

References

  • Abraham T, Allan SE, Levings MK (2010) Deconvolution and chromatic aberration corrections in quantifying colocalization of a transcription factor in three-dimensional cellular space. Micron 41(6):633–640

    Article  CAS  PubMed  Google Scholar 

  • Acharya S, Hill RA (2013) High efficacy gold-KDEL peptide-siRNA nanoconstruct-mediated transfection in C2C12 myoblasts and myotubes. Nanomedicine doi: 10.1016/j.nano.2013.07.015.doi epub ahead of print

  • Ando J, Fujita K, Smith NI, Kawata S (2011) Dynamic SERS imaging of cellular transport pathways with endocytosed gold nanoparticles. Nano Lett 11:5344–5348

    Article  CAS  PubMed  Google Scholar 

  • Akita H, Kogure K, Moriguchi R et al (2010) Nanoparticles for ex vivo siRNA delivery to dendritic cells for cancer vaccines: programmed endosomal escape and dissociation. J Control Rel 143(3):311–317

    Article  CAS  Google Scholar 

  • Akiyama T, Ishida J, Nakagawa S et al (1987) Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem 262(12):5592–5595

    CAS  PubMed  Google Scholar 

  • Badizadegan K, Wolf AA, Rodighiero C et al (2000) Floating cholera toxin into epithelial cells: functional association with caveolae-like detergent-insoluble membrane microdomains. Int J Med Microbiol 290(4–5):403–408

    Article  CAS  PubMed  Google Scholar 

  • Bae YM, Park YI, Nam SH et al (2012) Endocytosis, intracellular transport, and exocytosis of lanthanide-doped upconverting nanoparticles in single living cells. Biomaterials 33(35):9080–9086

    Article  CAS  PubMed  Google Scholar 

  • Behr JP (1997) The proton sponge: a trick to enter cells the viruses did not exploit. Chimia 51(1–2):34–36

    CAS  Google Scholar 

  • Benjaminsen RV, Mattebjerg MA, Henriksen JR et al (2013) The possible “proton sponge” effect of polyethylenimine (PEI) does not include change in lysosomal pH. Mol Ther 21(1):149–157

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bieber T, Meissner W, Kostin S et al (2002) Intracellular route and transcriptional competence of polyethylenimine-DNA complexes. J Control Release 82(2–3):441–454

    Article  CAS  PubMed  Google Scholar 

  • Bolte S, Cordelieres FP (2006) A guided tour into subcellular colocalization analysis in light microscopy. J Microsc 224(Pt 3):213–232

    Article  CAS  PubMed  Google Scholar 

  • Bradley JR, Johnson DR, Pober JS (1993) Four different classes of inhibitors of receptor-mediated endocytosis decrease tumor necrosis factor-induced gene expression in human endothelial cells. J Immunol 150(12):5544–5555

    CAS  PubMed  Google Scholar 

  • Braeckmans K, Buyens K, Naeye B et al (2010) Advanced fluorescence microscopy methods illuminate the transfection pathway of nucleic acid nanoparticles. J Control Rel 148(1):69–74

    Article  CAS  Google Scholar 

  • Bregar VB, Lojk J, Sustar V et al (2013) Visualization of internalization of functionalized cobalt ferrite nanoparticles and their intracellular fate. Int J Nanomed 8:919–931

    Google Scholar 

  • Brett JG, Godman GC (1984) Macrovacuolation induced by cytochalasin: its relation to the cytoskeleton; morphological and cytochemical observations. Tissue Cell 16(3):311–324

    Article  CAS  PubMed  Google Scholar 

  • Breuzard G, Tertil M, Goncalves C et al (2008) Nuclear delivery of NFkappaB-assisted DNA/polymer complexes: plasmid DNA quantitation by confocal laser scanning microscopy and evidence of nuclear polyplexes by FRET imaging. Nucleic Acids Res 36(12):e71

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Brodsky FM, Chen CY, Knuehl C et al (2001) Biological basket weaving: formation and function of clathrin-coated vesicles. Annu Rev Cell Dev Biol 17:517–568

    Article  CAS  PubMed  Google Scholar 

  • Brunner S, Sauer T, Carotta S et al (2000) Cell cycle dependence of gene transfer by lipoplex, polyplex and recombinant adenovirus. Gene Ther 7(5):401–407

    Article  CAS  PubMed  Google Scholar 

  • Canton I, Battaglia G (2012) Endocytosis at the nanoscale. Chem Soc Rev 41(7):2718–2739

    Article  CAS  PubMed  Google Scholar 

  • Chen L, Mccrate JM, Lee JC et al (2011) The role of surface charge on the uptake and biocompatibility of hydroxyapatite nanoparticles with osteoblast cells. Nanotechnology 22(10):105708

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Chernenko T, Matthaus C, Milane L et al (2009) Label-free Raman spectral imaging of intracellular delivery and degradation of polymeric nanoparticle systems. ACS Nano 3(11):3552–3559

    Article  CAS  PubMed  Google Scholar 

  • Chithrani BD, Chan WC (2007) Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes. Nano Lett 7(6):1542–1550

    Article  CAS  PubMed  Google Scholar 

  • Conner SD, Schmid SL (2003) Regulated portals of entry into the cell. Nature 422(6927):37–44

    Article  CAS  PubMed  Google Scholar 

  • Damke H, Baba T, van der Bliek AM et al (1995) Clathrin-independent pinocytosis is induced in cells overexpressing a temperature-sensitive mutant of dynamin. J Cell Biol 131(1):69–80

    Article  CAS  PubMed  Google Scholar 

  • Daukas G, Zigmond SH (1985) Inhibition of receptor-mediated but not fluid-phase endocytosis in polymorphonuclear leukocytes. J Cell Biol 101(5 Pt 1):1673–1679

    Article  CAS  PubMed  Google Scholar 

  • Dean DA, Strong DD, Zimmer WE (2005) Nuclear entry of nonviral vectors. Gene Ther 12(11):881–890

    Article  CAS  PubMed  Google Scholar 

  • Doherty GJ, McMahon HT (2009) Mechanisms of endocytosis. Annu Rev Biochem 78:857–902

    Article  CAS  PubMed  Google Scholar 

  • Dos ST, Varela J, Lynch I et al (2011) Effects of transport inhibitors on the cellular uptake of carboxylated polystyrene nanoparticles in different cell lines. PLoS ONE 6(9):e24438

    Article  CAS  Google Scholar 

  • Dowty ME, Williams P, Zhang G et al (1995) Plasmid DNA entry into postmitotic nuclei of primary rat myotubes. Proc Natl Acad Sci USA 92(10):4572–4576

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dunn KW, Kamocka MM, McDonald JH (2011) A practical guide to evaluating colocalization in biological microscopy. Am J Physiol Cell Physiol 300(4):C723–C742

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ehrlich M, Boll W, van Oijen A et al (2004) Endocytosis by random initiation and stabilization of clathrin-coated pits. Cell 118(5):591–605

    Article  CAS  PubMed  Google Scholar 

  • Fichter KM, Ingle NP, McLendon PM et al (2013) Polymeric nucleic acid vehicles exploit active interorganelle trafficking mechanisms. ACS Nano 7(1):347–364

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fletcher PA, Scriven DR, Schulson MN et al (2010) Multi-image colocalization and its statistical significance. Biophys J 99(6):1996–2005

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gabrielson NP, Pack DW (2009) Efficient polyethylenimine-mediated gene delivery proceeds via a caveolar pathway in HeLa cells. J Control Rel 136(1):54–61

    Article  CAS  Google Scholar 

  • Garcia GM, Alonso F, Chiva VA et al (1982) Phospholipid turnover during phagocytosis in human polymorphonuclear leucocytes. Biochem J 206(1):67–72

    Google Scholar 

  • Geisow MJ (1984) Fluorescein conjugates as indicators of subcellular Ph—a critical-evaluation. Exp Cell Res 150(1):29–35

    Article  CAS  PubMed  Google Scholar 

  • Georgieva JV, Kalicharan D, Couraud PO et al (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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Godbey WT, Wu KK, Mikos AG (1999) Tracking the intracellular path of poly(ethylenimine)/DNA complexes for gene delivery. Proc Natl Acad Sci USA 96(9):5177–5181

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gosselin MA, Guo W, Lee RJ (2001) Efficient gene transfer using reversibly cross-linked low molecular weight polyethylenimine. Bioconjug Chem 12(6):989–994

    Article  CAS  PubMed  Google Scholar 

  • Gratton SE, Ropp PA, Pohlhaus PD et al (2008) The effect of particle design on cellular internalization pathways. Proc Natl Acad Sci USA 105(33):11613–11618

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Grosse S, Aron Y, Thevenot G et al (2007) Cytoskeletal involvement in the cellular trafficking of plasmid/PEI derivative complexes. J Control Rel 122(1):111–117

    Article  CAS  Google Scholar 

  • Grossman E, Medalia O, Zwerger M (2012) Functional architecture of the nuclear pore complex. Annu Rev Biophys 41:557–584

    Article  CAS  PubMed  Google Scholar 

  • Gruenberg J, Stenmark H (2004) The biogenesis of multivesicular endosomes. Nat Rev Mol Cell Biol 5(4):317–323

    Article  CAS  PubMed  Google Scholar 

  • Hansen SH, Sandvig K, van Deurs B (1993) Clathrin and HA2 adaptors: effects of potassium depletion, hypertonic medium, and cytosol acidification. J Cell Biol 121(1):61–72

    Article  CAS  PubMed  Google Scholar 

  • Harris J, Werling D, Hope JC et al (2002) Caveolae and caveolin in immune cells: distribution and functions. Trends Immunol 23(3):158–164

    Article  CAS  PubMed  Google Scholar 

  • Harush-Frenkel O, Rozentur E, Benita S et al (2008) Surface charge of nanoparticles determines their endocytic and transcytotic pathway in polarized MDCK cells. Biomacromolecules 9(2):435–443

    Article  CAS  PubMed  Google Scholar 

  • Hasegawa S, Hirashima N, Nakanishi M (2001) Microtubule involvement in the intracellular dynamics for gene transfection mediated by cationic liposomes. Gene Ther 8(21):1669–1673

    Article  CAS  PubMed  Google Scholar 

  • He B, Lin P, Jia Z et al (2013) The transport mechanisms of polymer nanoparticles in Caco-2 epithelial cells. Biomaterials 34(25):6082–6098

    Article  CAS  PubMed  Google Scholar 

  • Heller A, Brockhoff G, Goepferich A (2012) Targeting drugs to mitochondria. Eur J Pharm Biopharm 82(1):1–18

    Article  CAS  PubMed  Google Scholar 

  • Hemmerich PH, von Mikecz AH (2013) Defining the subcellular interface of nanoparticles by live-cell imaging. PLoS ONE 8(4):e62018

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Henriques R, Griffiths C, Hesper RE et al (2011) PALM and STORM: unlocking live-cell super-resolution. Biopolymers 95(5):322–331

    Article  CAS  PubMed  Google Scholar 

  • Hinshaw JE (2000) Dynamin and its role in membrane fission. Annu Rev Cell Dev Biol 16:483–519

    Article  CAS  PubMed  Google Scholar 

  • Huang F, Khvorova A, Marshall W et al (2004) Analysis of clathrin-mediated endocytosis of epidermal growth factor receptor by RNA interference. J Biol Chem 279(16):16657–16661

    Article  CAS  PubMed  Google Scholar 

  • Hufnagel H, Hakim P, Lima A et al (2009) Fluid phase endocytosis contributes to transfection of DNA by PEI-25. Mol Ther 17(8):1411–1417

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ilina P, Hyvonen Z, Saura M et al (2012) Genetic blockage of endocytic pathways reveals differences in the intracellular processing of non-viral gene delivery systems. J Control Release 163(3):385–395

    Article  CAS  PubMed  Google Scholar 

  • Ivanov AI (2008) Pharmacological inhibition of endocytic pathways: is it specific enough to be useful? Method Mol Biol 440:15–33

    Article  CAS  Google Scholar 

  • Jones AT (2007) Macropinocytosis: searching for an endocytic identity and role in the uptake of cell penetrating peptides. J Cell Mol Med 11(4):670–684

    Article  CAS  PubMed  Google Scholar 

  • Kanzaki M, Pessin JE (2002) Caveolin-associated filamentous actin (Cav-actin) defines a novel F-actin structure in adipocytes. J Biol Chem 277(29):25867–25869

    Article  CAS  PubMed  Google Scholar 

  • Kerr MC, Teasdale RD (2009) Defining macropinocytosis. Traffic 10(4):364–371

    Article  CAS  PubMed  Google Scholar 

  • Khalil IA, Kogure K, Akita H et al (2006a) Uptake pathways and subsequent intracellular trafficking in nonviral gene delivery. Pharmacol Rev 58(1):32–45

    Article  CAS  PubMed  Google Scholar 

  • Khalil IA, Kogure K, Futaki S et al (2006b) High density of octaarginine stimulates macropinocytosis leading to efficient intracellular trafficking for gene expression. J Biol Chem 281(6):3544–3551

    Article  CAS  PubMed  Google Scholar 

  • Khalil IA, Kogure K, Futaki S et al (2008) Octaarginine-modified liposomes: enhanced cellular uptake and controlled intracellular trafficking. Int J Pharm 354(1–2):39–48

    Article  CAS  PubMed  Google Scholar 

  • Kilsdonk EP, Yancey PG, Stoudt GW et al (1995) Cellular cholesterol efflux mediated by cyclodextrins. J Biol Chem 270(29):17250–17256

    Article  CAS  PubMed  Google Scholar 

  • Kim AJ, Boylan NJ, Suk JS et al (2012) Non-degradative intracellular trafficking of highly compacted polymeric DNA nanoparticles. J Control Rel 158(1):102–107

    Article  CAS  Google Scholar 

  • Kirchhausen T (1999) Adaptors for clathrin-mediated traffic. Annu Rev Cell Dev Biol 15:705–732

    Article  CAS  PubMed  Google Scholar 

  • Larsen JD, Ross NL, Sullivan MO (2012) Requirements for the nuclear entry of polyplexes and nanoparticles during mitosis. J Gene Med 14(9–10):580–589

    Article  CAS  PubMed  Google Scholar 

  • Lechardeur D, Verkman AS, Lukacs GL (2005) Intracellular routing of plasmid DNA during non-viral gene transfer. Adv Drug Deliv Rev 57(5):755–767

    Article  CAS  PubMed  Google Scholar 

  • Lemmon SK (2001) Clathrin uncoating: Auxilin comes to life. Curr Biol 11(2):R49–R52

    Article  CAS  PubMed  Google Scholar 

  • Lencer WI, Hirst TR, Holmes RK (1999) Membrane traffic and the cellular uptake of cholera toxin. Biochim Biophys Acta 1450(3):177–190

    Article  CAS  PubMed  Google Scholar 

  • Leroueil PR, Hong S, Mecke A et al (2007) Nanoparticle interaction with biological membranes: does nanotechnology present a Janus face? Acc Chem Res 40(5):335–342

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Li W, Chen L, Huang Z et al (2011) The influence of cyclodextrin modification on cellular uptake and transfection efficiency of polyplexes. Org Biomol Chem 9(22):7799–7806

    Article  CAS  PubMed  Google Scholar 

  • Liao JK, Laufs U (2005) Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 45:89–118

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Luetterforst R, Stang E, Zorzi N et al (1999) Molecular characterization of caveolin association with the golgi complex: identification of a cis-golgi targeting domain in the caveolin molecule. J Cell Biol 145(7):1443–1459

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lundberg M, Johansson M (2001) Is VP22 nuclear homing an artifact? Nat Biotechnol 19(8):713–714

    Article  CAS  PubMed  Google Scholar 

  • Luzio JP, Pryor PR, Bright NA (2007) Lysosomes: fusion and function. Nat Rev Mol Cell Biol 8(8):622–632

    Article  CAS  PubMed  Google Scholar 

  • Ma Y, Greener T, Pacold ME et al (2002) Identification of domain required for catalytic activity of Auxilin in supporting clathrin uncoating by Hsc70. J Biol Chem 277(51):49267–49274

    Article  CAS  PubMed  Google Scholar 

  • Manders EM, Stap J, Brakenhoff GJ et al (1992) Dynamics of three-dimensional replication patterns during the S-phase, analysed by double labelling of DNA and confocal microscopy. J Cell Sci 103(3):857–862

    CAS  PubMed  Google Scholar 

  • Massignani M, LoPresti C, Blanazs A et al (2009) Controlling cellular uptake by surface chemistry, size, and surface topology at the nanoscale. Small 5(21):2424–2432

    Article  CAS  PubMed  Google Scholar 

  • Maxfield FR, McGraw TE (2004) Endocytic recycling. Nat Rev Mol Cell Biol 5(2):121–132

    Article  CAS  PubMed  Google Scholar 

  • McNally JG, Karpova T, Cooper J et al (1999) Three-dimensional imaging by deconvolution microscopy. Methods 19(3):373–385

    Article  CAS  PubMed  Google Scholar 

  • Mercer J, Helenius A (2009) Virus entry by macropinocytosis. Nat Cell Biol 11(5):510–520

    Article  CAS  PubMed  Google Scholar 

  • Mettlen M, Platek A, Van Der Smissen P et al (2006) Src triggers circular ruffling and macropinocytosis at the apical surface of polarized MDCK cells. Traffic 7(5):589–603

    Article  CAS  PubMed  Google Scholar 

  • Moreno-Ruiz E, Galan-Diez M, Zhu W et al (2009) Candida albicans internalization by host cells is mediated by a clathrin-dependent mechanism. Cell Microbiol 11(8):1179–1189

    Article  CAS  PubMed  Google Scholar 

  • Nakai T, Kanamori T, Sando S et al (2003) Remarkably size-regulated cell invasion by artificial viruses. Saccharide-dependent self-aggregation of glycoviruses and its consequences in glycoviral gene delivery. J Am Chem Soc 125(28):8465–8475

    Article  CAS  PubMed  Google Scholar 

  • Nakase I, Niwa M, Takeuchi T et al (2004) Cellular uptake of arginine-rich peptides: roles for macropinocytosis and actin rearrangement. Mol Ther 10(6):1011–1022

    Article  CAS  PubMed  Google Scholar 

  • Ogris M, Wagner E, Steinlein P (2000) A versatile assay to study cellular uptake of gene transfer complexes by flow cytometry. Biochim Biophys Acta 1474(2):237–243

    Article  CAS  PubMed  Google Scholar 

  • Paine PL, Moore LC, Horowitz SB (1975) Nuclear envelope permeability. Nature 254(5496):109–114

    Article  CAS  PubMed  Google Scholar 

  • Pante N, Kann M (2002) Nuclear pore complex is able to transport macromolecules with diameters of about 39 nm. Mol Biol Cell 13(2):425–434

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Parton RG, Joggerst B, Simons K (1994) Regulated internalization of caveolae. J Cell Biol 127(5):1199–1215

    Article  CAS  PubMed  Google Scholar 

  • Parton RG, Richards AA (2003) Lipid rafts and caveolae as portals for endocytosis: new insights and common mechanisms. Traffic 4(11):724–738

    Article  CAS  PubMed  Google Scholar 

  • Parton RG, Simons K (2007) The multiple faces of caveolae. Nat Rev Mol Cell Biol 8(3):185–194

    Article  CAS  PubMed  Google Scholar 

  • Pearson H (2007) The good, the bad and the ugly. Nature 447(7141):138–140

    Article  CAS  PubMed  Google Scholar 

  • Pelkmans L, Kartenbeck J, Helenius A (2001) Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER. Nat Cell Biol 3(5):473–483

    Article  CAS  PubMed  Google Scholar 

  • Perumal OP, Inapagolla R, Kannan S et al (2008) The effect of surface functionality on cellular trafficking of dendrimers. Biomaterials 29(24–25):3469–3476

    Article  CAS  PubMed  Google Scholar 

  • Phizicky E, Bastiaens PI, Zhu H et al (2003) Protein analysis on a proteomic scale. Nature 422(6928):208–215

    Article  CAS  PubMed  Google Scholar 

  • Pollard H, Remy JS, Loussouarn G et al (1998) Polyethylenimine but not cationic lipids promotes transgene delivery to the nucleus in mammalian cells. J Biol Chem 273(13):7507–7511

    Article  CAS  PubMed  Google Scholar 

  • Rejman J, Oberle V, Zuhorn IS et al (2004) Size-dependent internalization of particles via the pathways of clathrin- and caveolae-mediated endocytosis. Biochem J 377(Pt 1):159–169

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Roberts RL, Nath J, Friedman MM et al (1982) Effects of taxol on human neutrophils. J Immunol 129(5):2134–2141

    CAS  PubMed  Google Scholar 

  • Rodal SK, Skretting G, Garred O et al (1999) Extraction of cholesterol with methyl-beta-cyclodextrin perturbs formation of clathrin-coated endocytic vesicles. Mol Biol Cell 10(4):961–974

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ros-Baro A, Lopez-Iglesias C, Peiro S et al (2001) Lipid rafts are required for GLUT4 internalization in adipose cells. Proc Natl Acad Sci USA 98(21):12050–12055

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rothberg KG, Ying YS, Kolhouse JF et al (1990) The glycophospholipid-linked folate receptor internalizes folate without entering the clathrin-coated pit endocytic pathway. J Cell Biol 110(3):637–649

    Article  CAS  PubMed  Google Scholar 

  • Ruthardt N, Brauchle C (2010) Visualizing uptake and intracellular trafficking of gene carriers by single-particle tracking. Top Curr Chem 296:283–304

    Article  CAS  PubMed  Google Scholar 

  • Saftig P, Klumperman J (2009) Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function. Nat Rev Mol Cell Biol 10(9):623–635

    Article  CAS  PubMed  Google Scholar 

  • Sakhrani NM, Padh H (2013) Organelle targeting: third level of drug targeting. Drug Des Dev Ther 7:585–599

    CAS  Google Scholar 

  • Salh B, Wagey R, Marotta A et al (1998) Activation of phosphatidylinositol 3-kinase, protein kinase B, and p70 S6 kinases in lipopolysaccharide-stimulated Raw 264.7 cells: differential effects of rapamycin, Ly294002, and wortmannin on nitric oxide production. J Immunol 161(12):6947–6954

    CAS  PubMed  Google Scholar 

  • Salvati A, Aberg C, dos Santos T et al (2011) Experimental and theoretical comparison of intracellular import of polymeric nanoparticles and small molecules: toward models of uptake kinetics. Nanomedicine 7(6):818–826

    Article  CAS  PubMed  Google Scholar 

  • Sandvig K, Olsnes S, Petersen OW et al (1987) Acidification of the cytosol inhibits endocytosis from coated pits. J Cell Biol 105(2):679–689

    Article  CAS  PubMed  Google Scholar 

  • Schmid SL (1997) Clathrin-coated vesicle formation and protein sorting: an integrated process. Annu Rev Biochem 66:511–548

    Article  CAS  PubMed  Google Scholar 

  • Schnitzer JE, Allard J, Oh P (1995) NEM inhibits transcytosis, endocytosis, and capillary permeability: implication of caveolae fusion in endothelia. Am J Physiol 268(2):H48–H55

    CAS  PubMed  Google Scholar 

  • Scriven DR, Lynch RM, Moore ED (2008) Image acquisition for colocalization using optical microscopy. Am J Physiol Cell Physiol 294(5):C1119–C1122

    Article  CAS  PubMed  Google Scholar 

  • Shi J, Chou B, Choi JL et al (2013) Investigation of polyethylenimine/DNA polyplex transfection to cultured cells using radiolabeling and subcellular fractionation methods. Mol Pharm 10(6):2145–2156

    Article  CAS  PubMed  Google Scholar 

  • Smart EJ, Ying YS, Conrad PA et al (1994) Caveolin moves from caveolae to the golgi apparatus in response to cholesterol oxidation. J Cell Biol 127(5):1185–1197

    Article  CAS  PubMed  Google Scholar 

  • Spoden G, Freitag K, Husmann M et al (2008) Clathrin- and caveolin-independent entry of human papillomavirus type 16–involvement of tetraspanin-enriched microdomains (TEMs). PLoS ONE 3(10):e3313

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Stoorvogel W, Strous GJ, Geuze HJ et al (1991) Late endosomes derive from early endosomes by maturation. Cell 65(3):417–427

    Article  CAS  PubMed  Google Scholar 

  • Suh J, An Y, Tang BC et al (2012) Real-time gene delivery vector tracking in the endo-lysosomal pathway of live cells. Microsc Res Tech 75(5):691–697

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Suh J, Wirtz D, Hanes J (2003) Efficient active transport of gene nanocarriers to the cell nucleus. Proc Natl Acad Sci USA 100(7):3878–3882

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Thorek DL, Tsourkas A (2008) Size, charge and concentration dependent uptake of iron oxide particles by non-phagocytic cells. Biomaterials 29(26):3583–3590

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Treuel L, Jiang X, Nienhaus GU (2013) New views on cellular uptake and trafficking of manufactured nanoparticles. J Royal Soc Interface 10(82):20120939

    Article  CAS  Google Scholar 

  • van der Aa MA, Huth US, Hafele SY et al (2007) Cellular uptake of cationic polymer-DNA complexes via caveolae plays a pivotal role in gene transfection in COS-7 cells. Pharm Res 24(8):1590–1598

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Vaughan EE, Dean DA (2006) Intracellular trafficking of plasmids during transfection is mediated by microtubules. Mol Ther 13(2):422–428

    Article  CAS  PubMed  Google Scholar 

  • Veiga E, Cossart P (2005) Listeria hijacks the clathrin-dependent endocytic machinery to invade mammalian cells. Nat Cell Biol 7(9):894–900

    Article  CAS  PubMed  Google Scholar 

  • Vercauteren D, Rejman J, Martens TF et al (2012) On the cellular processing of non-viral nanomedicines for nucleic acid delivery: mechanisms and methods. J Control Rel 161(2):566–581

    Article  CAS  Google Scholar 

  • Vercauteren D, Vandenbroucke RE, Jones AT et al (2010) The use of inhibitors to study endocytic pathways of gene carriers: optimization and pitfalls. Mol Ther 18(3):561–569

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Vida T, Gerhardt B (1999) A cell-free assay allows reconstitution of Vps33p-dependent transport to the yeast vacuole/lysosome. J Cell Biol 146(1):85–98

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Villanueva A, Canete M, Roca AG et al (2009) The influence of surface functionalization on the enhanced internalization of magnetic nanoparticles in cancer cells. Nanotechnology 20(11):115103

    Article  PubMed  CAS  Google Scholar 

  • Visser CC, Stevanovic S, Heleen VL et al (2004) Validation of the transferrin receptor for drug targeting to brain capillary endothelial cells in vitro. J Drug Target 12(3):145–150

    Article  CAS  PubMed  Google Scholar 

  • von Gersdorff K, Sanders NN, Vandenbroucke R et al (2006) The internalization route resulting in successful gene expression depends on both cell line and polyethylenimine polyplex type. Mol Ther 14(5):745–753

    Article  CAS  Google Scholar 

  • Wang AZ (2012) Nanoparticle drug delivery: focusing on the therapeutic cargo. Nanomedicine (Lond.) 7(10):1463–1465

    Article  CAS  Google Scholar 

  • Wang G, Norton AS, Pokharel D et al (2013) KDEL peptide gold nanoconstructs: promising nanoplatforms for drug delivery. Nanomedicine 9(3):366–374

    Article  CAS  PubMed  Google Scholar 

  • Wang LH, Rothberg KG, Anderson RG (1993) Mis-assembly of clathrin lattices on endosomes reveals a regulatory switch for coated pit formation. J Cell Biol 123(5):1107–1117

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Tiruppathi C, Minshall RD et al (2009) Size and dynamics of caveolae studied using nanoparticles in living endothelial cells. ACS Nano 3(12):4110–4116

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wasungu L, Hoekstra D (2006) Cationic lipids, lipoplexes and intracellular delivery of genes. J Control Rel 116(2):255–264

    Article  CAS  Google Scholar 

  • West MA, Bretscher MS, Watts C (1989) Distinct endocytotic pathways in epidermal growth factor-stimulated human carcinoma A431 cells. J Cell Biol 109(1):2731–2739

    Article  CAS  PubMed  Google Scholar 

  • Westermann M, Steiniger F, Richter W (2005) Belt-like localisation of caveolin in deep caveolae and its re-distribution after cholesterol depletion. Histochem Cell Biol 123(6):613–620

    Article  CAS  PubMed  Google Scholar 

  • Yumoto R, Nishikawa H, Okamoto M et al (2006) Clathrin-mediated endocytosis of FITC-albumin in alveolar type II epithelial cell line RLE-6TN. Am J Physiol Lung Cell Mol Physiol 290(5):L946–L955

    Article  CAS  PubMed  Google Scholar 

  • Zaki NM, Tirelli N (2010) Gateways for the intracellular access of nanocarriers: a review of receptor-mediated endocytosis mechanisms and of strategies in receptor targeting. Expert Opin Drug Deliv 7(8):895–913

    Article  CAS  PubMed  Google Scholar 

  • Zauner W, Farrow NA, Haines AM (2001) In vitro uptake of polystyrene microspheres: effect of particle size, cell line and cell density. J Control Rel 71(1):39–51

    Article  CAS  Google Scholar 

  • Zhao F, Zhao Y, Liu Y et al (2011) Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials. Small 7(10):1322–1337

    Article  CAS  PubMed  Google Scholar 

  • Zuidam NJ, Posthuma G, de Vries ET et al (2000) Effects of physicochemical characteristics of poly(2-(dimethylamino)ethyl methacrylate)-based polyplexes on cellular association and internalization. J Drug Target 8(1):51–66

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

Financial support by the Danish Agency for Science, Technology and Innovation (Det Frie Forskningsrå for Teknologi og Produktion) reference 274-08-0534 is gratefully acknowledged.

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Authors and Affiliations

  1. Nanomedicine Research Group, Centre for Pharmaceutical Nanotechnology and Nanotoxicology, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen, Denmark

    Helene Andersen, Ladan Parhamifar & S. Moein Moghimi

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  1. Helene Andersen
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  2. Ladan Parhamifar
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  3. S. Moein Moghimi
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Correspondence to S. Moein Moghimi .

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Editors and Affiliations

  1. Chemical and Biological Engineering, Vanderbilt University, Nashville, Tennessee, USA

    Aleš Prokop

  2. Chemistry and Materials Engineering, Kansai University, Osaka, Japan

    Yasuhiko Iwasaki

  3. Department of Applied Chemistry, Osaka Prefecture University, Osaka, Japan

    Atsushi Harada

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Andersen, H., Parhamifar, L., Moein Moghimi, S. (2014). Uptake and Intracellular Trafficking of Nanocarriers. In: Prokop, A., Iwasaki, Y., Harada, A. (eds) Intracellular Delivery II. Fundamental Biomedical Technologies, vol 7. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8896-0_6

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