Cancer-Specific Ligand–Receptor Interactions

  • Ewelina Kluza
  • Gustav J. Strijkers
  • Regina G. H. Beets-Tan
  • Klaas Nicolay
Chapter

Abstract

The concept of cancer targeting, which exploits the abundance of specific molecular epitopes on cancer cells, has been proposed as a strategy to enhance the efficacy and specificity of cancer therapy and diagnostics. Although many promising results have been obtained with this approach, the research experience of the last decades demonstrates clearly the challenges that the clinical application of cancer-targeted approaches faces. This can be attributed to both the complexity of targeted probe–cell interactions as well as the multitude of additional factors, which influence the efficacy of the targeting process. The aim of this chapter is to address the key steps involved in the cellular pathway of ligand-functionalized probes for cancer targeting. Special attention is given to nanoparticulate delivery systems as the most commonly exploited formulations for cancer targeting. Their interaction with target cells is initiated by ligand binding to the cell surface receptor, which is frequently followed by endocytosis of ligand–receptor complex and, in the final phase, by lysosomal degradation. All the aforementioned processes are presented in view of the pathophysiological and molecular features of the biological system as well as the physicochemical and biological properties of targeted probes. Importantly, we discuss the implications of these intracellular events for the therapeutic activity and diagnostic capabilities of targeted agents.

Keywords

Lipase Chitosan Influenza Oligomer Doxorubicin 

References

  1. 1.
    de Wever O, Mareel M (2003) Role of tissue stroma in cancer cell invasion. J Pathol 200:429–447PubMedGoogle Scholar
  2. 2.
    Cai W, Niu G, Chen X (2008) Multimodality imaging of the HER-kinase axis in cancer. Eur J Nucl Med Mol Imaging 35:186–208PubMedGoogle Scholar
  3. 3.
    Arteaga C (2003) Targeting HER1/EGFR: a molecular approach to cancer therapy. Semin Oncol 30:3–14Google Scholar
  4. 4.
    Koeppen HK, Wright BD, Burt AD et al (2001) Overexpression of HER2/neu in solid tumours: an immunohistochemical survey. Histopathology 38:96–104PubMedGoogle Scholar
  5. 5.
    Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182PubMedGoogle Scholar
  6. 6.
    Low PS, Henne WA, Doorneweerd DD (2008) Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases. Acc Chem Res 41:120–129PubMedGoogle Scholar
  7. 7.
    Jones DT, Trowbridge IS, Harris AL (2006) Effects of transferrin receptor blockade on cancer cell proliferation and hypoxia-inducible factor function and their differential regulation by ascorbate. Cancer Res 66:2749–2756PubMedGoogle Scholar
  8. 8.
    Gunthert U, Hofmann M, Rudy W et al (1991) A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell 65:13–24PubMedGoogle Scholar
  9. 9.
    Heinlein CA, Chang C (2004) Androgen receptor in prostate cancer. Endocr Rev 25:276–308PubMedGoogle Scholar
  10. 10.
    Lee P, Rosen DG, Zhu C, Silva EG, Liu J (2005) Expression of progesterone receptor is a favorable prognostic marker in ovarian cancer. Gynecol Oncol 96:671–677PubMedGoogle Scholar
  11. 11.
    Fuqua SA, Cui Y, Lee AV, Osborne CK, Horwitz KB (2005) Insights into the role of progesterone receptors in breast cancer. J Clin Oncol 23:931–932, author reply 932–933PubMedGoogle Scholar
  12. 12.
    Sommer S, Fuqua SA (2001) Estrogen receptor and breast cancer. Semin Cancer Biol 11:339–352PubMedGoogle Scholar
  13. 13.
    Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186PubMedGoogle Scholar
  14. 14.
    Ferrara N, Kerbel RS (2005) Angiogenesis as a therapeutic target. Nature 438:967–974PubMedGoogle Scholar
  15. 15.
    Neeman M, Gilad AA, Dafni H, Cohen B (2007) Molecular imaging of angiogenesis. J Magn Reson Imaging 25:1–12PubMedGoogle Scholar
  16. 16.
    Adams RH, Alitalo K (2007) Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol 8:464–478PubMedGoogle Scholar
  17. 17.
    Avraamides CJ, Garmy-Susini B, Varner JA (2008) Integrins in angiogenesis and lymphangiogenesis. Nat Rev Cancer 8:604–617PubMedCentralPubMedGoogle Scholar
  18. 18.
    Ferrara N, Hillan KJ, Gerber HP, Novotny W (2004) Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 3:391–400PubMedGoogle Scholar
  19. 19.
    Hattori K, Heissig B, Wu Y et al (2002) Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat Med 8:841–849PubMedCentralPubMedGoogle Scholar
  20. 20.
    Gerber HP, Malik AK, Solar GP et al (2002) VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism. Nature 417:954–958PubMedGoogle Scholar
  21. 21.
    Barleon B, Sozzani S, Zhou D, Weich HA, Mantovani A, Marme D (1996) Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. Blood 87:3336–3343PubMedGoogle Scholar
  22. 22.
    Luttun A, Tjwa M, Moons L et al (2002) Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat Med 8:831–840PubMedGoogle Scholar
  23. 23.
    Hiratsuka S, Nakamura K, Iwai S et al (2002) MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis. Cancer Cell 2:289–300PubMedGoogle Scholar
  24. 24.
    LeCouter J, Moritz DR, Li B et al (2003) Angiogenesis-independent endothelial protection of liver: role of VEGFR-1. Science 299:890–893PubMedGoogle Scholar
  25. 25.
    Brooks PC, Clark RA, Cheresh DA (1994) Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science 264:569–571PubMedGoogle Scholar
  26. 26.
    Cheresh DA (1987) Human endothelial cells synthesize and express an Arg-Gly-Asp-directed adhesion receptor involved in attachment to fibrinogen and von Willebrand factor. Proc Natl Acad Sci USA 84:6471–6475PubMedGoogle Scholar
  27. 27.
    Ruoslahti E, Pierschbacher MD (1986) Arg-Gly-Asp: a versatile cell recognition signal. Cell 44:517–518PubMedGoogle Scholar
  28. 28.
    Sipkins DA, Cheresh DA, Kazemi MR, Nevin LM, Bednarski MD, Li KC (1998) Detection of tumor angiogenesis in vivo by alphaVbeta3-targeted magnetic resonance imaging. Nat Med 4:623–626PubMedGoogle Scholar
  29. 29.
    Haubner R, Wester H-J, Weber WA et al (2001) Noninvasive imaging of αvβ3 integrin expression using 18F-labeled RGD-containing glycopeptide and positron emission tomography. Cancer Res 61:1781–1785PubMedGoogle Scholar
  30. 30.
    Leong-Poi H, Christiansen J, Klibanov AL, Kaul S, Lindner JR (2003) Noninvasive assessment of angiogenesis by ultrasound and microbubbles targeted to αv-integrins. Circulation 107:455–460PubMedGoogle Scholar
  31. 31.
    Thijssen VL, Postel R, Brandwijk RJ et al (2006) Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy. Proc Natl Acad Sci USA 103:15975–15980PubMedGoogle Scholar
  32. 32.
    Alitalo K, Tammela T, Petrova TV (2005) Lymphangiogenesis in development and human disease. Nature 438:946–953PubMedGoogle Scholar
  33. 33.
    Achen MG, Stacker SA (2008) Molecular control of lymphatic metastasis. Ann N Y Acad Sci 1131:225–234PubMedGoogle Scholar
  34. 34.
    Tobler NE, Detmar M (2006) Tumor and lymph node lymphangiogenesis – impact on cancer metastasis. J Leukoc Biol 80:691–696PubMedGoogle Scholar
  35. 35.
    Dadras SS, Lange-Asschenfeldt B, Velasco P et al (2005) Tumor lymphangiogenesis predicts melanoma metastasis to sentinel lymph nodes. Mod Pathol 18:1232–1242PubMedGoogle Scholar
  36. 36.
    He Y, Kozaki K, Karpanen T et al (2002) Suppression of tumor lymphangiogenesis and lymph node metastasis by blocking vascular endothelial growth factor receptor 3 signaling. J Natl Cancer Inst 94:819–825PubMedGoogle Scholar
  37. 37.
    Jackson DG (2004) Biology of the lymphatic marker LYVE-1 and applications in research into lymphatic trafficking and lymphangiogenesis. APMIS 112:526–538PubMedGoogle Scholar
  38. 38.
    Breiteneder-Geleff S, Soleiman A, Kowalski H et al (1999) Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: podoplanin as a specific marker for lymphatic endothelium. Am J Pathol 154:385–394PubMedGoogle Scholar
  39. 39.
    Schacht V, Ramirez MI, Hong YK et al (2003) T1alpha/podoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema. EMBO J 22:3546–3556PubMedGoogle Scholar
  40. 40.
    Kalluri R, Zeisberg M (2006) Fibroblasts in cancer. Nat Rev Cancer 6:392–401PubMedGoogle Scholar
  41. 41.
    Rettig WJ, Garin-Chesa P, Healey JH et al (1993) Regulation and heteromeric structure of the fibroblast activation protein in normal and transformed cells of mesenchymal and neuroectodermal origin. Cancer Res 53:3327–3335PubMedGoogle Scholar
  42. 42.
    Wang XM, Yu DM, McCaughan GW, Gorrell MD (2005) Fibroblast activation protein increases apoptosis, cell adhesion, and migration by the LX-2 human stellate cell line. Hepatology 42:935–945PubMedGoogle Scholar
  43. 43.
    Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867PubMedCentralPubMedGoogle Scholar
  44. 44.
    Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454:436–444PubMedGoogle Scholar
  45. 45.
    Heusinkveld M, van der Burg SH (2011) Identification and manipulation of tumor associated macrophages in human cancers. J Transl Med 9:216PubMedCentralPubMedGoogle Scholar
  46. 46.
    Verreck FA, de Boer T, Langenberg DM, van der Zanden L, Ottenhoff TH (2006) Phenotypic and functional profiling of human proinflammatory type-1 and anti-inflammatory type-2 macrophages in response to microbial antigens and IFN-gamma- and CD40L-mediated costimulation. J Leukoc Biol 79:285–293PubMedGoogle Scholar
  47. 47.
    Biswas SK, Mantovani A (2010) Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol 11:889–896PubMedGoogle Scholar
  48. 48.
    Fogal V, Zhang L, Krajewski S, Ruoslahti E (2008) Mitochondrial/cell-surface protein p32/gC1qR as a molecular target in tumor cells and tumor stroma. Cancer Res 68:7210–7218PubMedCentralPubMedGoogle Scholar
  49. 49.
    Parsons SL, Watson SA, Collins HM, Griffin NR, Clarke PA, Steele RJ (1998) Gelatinase (MMP-2 and -9) expression in gastrointestinal malignancy. Br J Cancer 78:1495–1502PubMedCentralPubMedGoogle Scholar
  50. 50.
    Kovar JL, Johnson MA, Volcheck WM, Chen J, Simpson MA (2006) Hyaluronidase expression induces prostate tumor metastasis in an orthotopic mouse model. Am J Pathol 169:1415–1426PubMedGoogle Scholar
  51. 51.
    Warenius HM, Galfre G, Bleehen NM, Milstein C (1981) Attempted targeting of A monoclonalantibody in a human-tumor xenograft system. Eur J Cancer Clin Oncol 17:1009–1015PubMedGoogle Scholar
  52. 52.
    Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2:751–760PubMedGoogle Scholar
  53. 53.
    Albanell J, Baselga J (1999) Trastuzumab, a humanized anti-HER2 monoclonal antibody, for the treatment of breast cancer. Drugs Today (Barc) 35:931–946Google Scholar
  54. 54.
    Marks JD, Ouwehand WH, Bye JM et al (1993) Human antibody fragments specific for human blood group antigens from a phage display library. Biotechnology (NY) 11:1145–1149Google Scholar
  55. 55.
    Marks JD (2004) Selection of internalizing antibodies for drug delivery. Methods Mol Biol 248:201–208PubMedGoogle Scholar
  56. 56.
    Liu B, Conrad F, Cooperberg MR, Kirpotin DB, Marks JD (2004) Mapping tumor epitope space by direct selection of single-chain Fv antibody libraries on prostate cancer cells. Cancer Res 64:704–710PubMedGoogle Scholar
  57. 57.
    Kiessling LL, Gestwicki JE, Strong LE (2000) Synthetic multivalent ligands in the exploration of cell-surface interactions. Curr Opin Chem Biol 4:696–703PubMedGoogle Scholar
  58. 58.
    Todorovska A, Roovers RC, Dolezal O, Kortt AA, Hoogenboom HR, Hudson PJ (2001) Design and application of diabodies, triabodies and tetrabodies for cancer targeting. J Immunol Methods 248:47–66PubMedGoogle Scholar
  59. 59.
    Pasqualini R, Ruoslahti E (1996) Organ targeting in vivo using phage display peptide libraries. Nature 380:364–366PubMedGoogle Scholar
  60. 60.
    Eliaz RE, Szoka FC Jr (2001) Liposome-encapsulated doxorubicin targeted to CD44: a strategy to kill CD44-overexpressing tumor cells. Cancer Res 61:2592–2601PubMedGoogle Scholar
  61. 61.
    Shiftan L, Israely T, Cohen M et al (2005) Magnetic resonance imaging visualization of hyaluronidase in ovarian carcinoma. Cancer Res 65:10316–10323PubMedGoogle Scholar
  62. 62.
    Agrawal P, Strijkers GJ, Nicolay K (2010) Chitosan-based systems for molecular imaging. Adv Drug Deliv Rev 62:42–58PubMedGoogle Scholar
  63. 63.
    Ferrari M (2005) Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer 5:161–171PubMedGoogle Scholar
  64. 64.
    Torchilin VP (2005) Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 4:145–160PubMedGoogle Scholar
  65. 65.
    Kato K, Hamaguchi T, Yasui H et al (2006) Phase I study of NK105, a paclitaxel-incorporating micellar nanoparticle, in patients with advanced cancer. J Clin Oncol 24:83SGoogle Scholar
  66. 66.
    Damascelli B, Cantu G, Mattavelli F et al (2001) Intraarterial chemotherapy with polyoxyethylated castor oil free paclitaxel, incorporated in albumin nanoparticles (ABI-007): Phase II study of patients with squamous cell carcinoma of the head and neck and anal canal: preliminary evidence of clinical activity. Cancer 92:2592–2602PubMedGoogle Scholar
  67. 67.
    Morawski AM, Lanza GA, Wickline SA (2005) Targeted contrast agents for magnetic resonance imaging and ultrasound. Curr Opin Biotechnol 16:89–92PubMedGoogle Scholar
  68. 68.
    Loo C, Lowery A, Halas N, West J, Drezek R (2005) Immunotargeted nanoshells for integrated cancer imaging and therapy. Nano Lett 5:709–711PubMedGoogle Scholar
  69. 69.
    Chen J, Saeki F, Wiley BJ et al (2005) Gold nanocages: bioconjugation and their potential use as optical imaging contrast agents. Nano Lett 5:473–477PubMedGoogle Scholar
  70. 70.
    Hrkach J, Von Hoff D, Mukkaram Ali M et al (2012) Preclinical development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile. Sci Transl Med 4:128ra139Google Scholar
  71. 71.
    Gu F, Zhang L, Teply BA et al (2008) Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers. Proc Natl Acad Sci USA 105:2586–2591PubMedGoogle Scholar
  72. 72.
    Siegwart DJ, Whitehead KA, Nuhn L et al (2011) Combinatorial synthesis of chemically diverse core-shell nanoparticles for intracellular delivery. Proc Natl Acad Sci USA 108:12996–13001PubMedGoogle Scholar
  73. 73.
    Weissleder R, Kelly K, Sun EY, Shtatland T, Josephson L (2005) Cell-specific targeting of nanoparticles by multivalent attachment of small molecules. Nat Biotechnol 23:1418–1423PubMedGoogle Scholar
  74. 74.
    Wang H, Liu K, Chen KJ et al (2010) A rapid pathway toward a superb gene delivery system: programming structural and functional diversity into a supramolecular nanoparticle library. ACS Nano 4:6235–6243PubMedCentralPubMedGoogle Scholar
  75. 75.
    Adams GP, Schier R, McCall AM et al (2001) High affinity restricts the localization and tumor penetration of single-chain fv antibody molecules. Cancer Res 61:4750–4755PubMedGoogle Scholar
  76. 76.
    Cressman S, Sun Y, Maxwell E, Fang N, Chen D, Cullis P (2009) Binding and uptake of RGD-containing ligands to cellular α ν β 3 integrins. Int J Pept Res Ther 15:49–59Google Scholar
  77. 77.
    Rudnick SI, Adams GP (2009) Affinity and avidity in antibody-based tumor targeting. Cancer Biother Radiopharm 24:155–161PubMedGoogle Scholar
  78. 78.
    Baker JH, Lindquist KE, Huxham LA, Kyle AH, Sy JT, Minchinton AI (2008) Direct visualization of heterogeneous extravascular distribution of trastuzumab in human epidermal growth factor receptor type 2 overexpressing xenografts. Clin Cancer Res 14:2171–2179PubMedGoogle Scholar
  79. 79.
    Fujimori K, Covell DG, Fletcher JE, Weinstein JN (1989) Modeling analysis of the global and microscopic distribution of immunoglobulin G, F(ab')2, and Fab in tumors. Cancer Res 49:5656–5663PubMedGoogle Scholar
  80. 80.
    Juweid M, Neumann R, Paik C et al (1992) Micropharmacology of monoclonal antibodies in solid tumors: direct experimental evidence for a binding site barrier. Cancer Res 52:5144–5153PubMedGoogle Scholar
  81. 81.
    Saga T, Neumann RD, Heya T et al (1995) Targeting cancer micrometastases with monoclonal antibodies: a binding-site barrier. Proc Natl Acad Sci USA 92:8999–9003PubMedGoogle Scholar
  82. 82.
    Schier R, Bye J, Apell G et al (1996) Isolation of high-affinity monomeric human anti-c-erbB-2 single chain Fv using affinity-driven selection. J Mol Biol 255:28–43PubMedGoogle Scholar
  83. 83.
    Mulder WJ, Strijkers GJ, Habets JW et al (2005) MR molecular imaging and fluorescence microscopy for identification of activated tumor endothelium using a bimodal lipidic nanoparticle. FASEB J 19:2008–2010PubMedGoogle Scholar
  84. 84.
    Schmieder AH, Caruthers SD, Zhang H et al (2008) Three-dimensional MR mapping of angiogenesis with alpha5beta1(alpha nu beta3)-targeted theranostic nanoparticles in the MDA-MB-435 xenograft mouse model. FASEB J 22:4179–4189PubMedGoogle Scholar
  85. 85.
    Backer MV, Levashova Z, Patel V et al (2007) Molecular imaging of VEGF receptors in angiogenic vasculature with single-chain VEGF-based probes. Nat Med 13:504–509PubMedGoogle Scholar
  86. 86.
    Yang L, Peng XH, Wang YA et al (2009) Receptor-targeted nanoparticles for in vivo imaging of breast cancer. Clin Cancer Res 15:4722–4732PubMedCentralPubMedGoogle Scholar
  87. 87.
    Dublin E, Hanby A, Patel NK, Liebman R, Barnes D (2000) Immunohistochemical expression of uPA, uPAR, and PAI-1 in breast carcinoma. Fibroblastic expression has strong associations with tumor pathology. Am J Pathol 157:1219–1227PubMedGoogle Scholar
  88. 88.
    Heldin CH, Rubin K, Pietras K, Ostman A (2004) High interstitial fluid pressure – an obstacle in cancer therapy. Nat Rev Cancer 4:806–813PubMedGoogle Scholar
  89. 89.
    Moghimi SM, Hunter AC, Andresen TL (2012) Factors controlling nanoparticle pharmacokinetics: an integrated analysis and perspective. Annu Rev Pharmacol Toxicol 52:481–503PubMedGoogle Scholar
  90. 90.
    Kyriakos RJ, Shih LB, Ong GL, Patel K, Goldenberg DM, Mattes MJ (1992) The fate of antibodies bound to the surface of tumor cells in vitro. Cancer Res 52:835–842PubMedGoogle Scholar
  91. 91.
    Handl HL, Vagner J, Han H, Mash E, Hruby VJ, Gillies RJ (2004) Hitting multiple targets with multimeric ligands. Expert Opin Ther Targets 8:565–586PubMedGoogle Scholar
  92. 92.
    Hong S, Leroueil PR, Majoros IJ, Orr BG, Baker JR Jr, Banaszak Holl MM (2007) The binding avidity of a nanoparticle-based multivalent targeted drug delivery platform. Chem Biol 14:107–115PubMedGoogle Scholar
  93. 93.
    Kok MB, Hak S, Mulder WJ, van der Schaft DW, Strijkers GJ, Nicolay K (2009) Cellular compartmentalization of internalized paramagnetic liposomes strongly influences both T1 and T2 relaxivity. Magn Reson Med 61:1022–1032PubMedGoogle Scholar
  94. 94.
    Moradi E, Vllasaliu D, Garnett M, Falcone F, Stolnik S (2012) Ligand density and clustering effects on endocytosis of folate modified nanoparticles. RSC Adv 2:3025–3033Google Scholar
  95. 95.
    Bandyopadhyay A, Fine RL, Demento S, Bockenstedt LK, Fahmy TM (2011) The impact of nanoparticle ligand density on dendritic-cell targeted vaccines. Biomaterials 32:3094–3105PubMedGoogle Scholar
  96. 96.
    Elias DR, Poloukhtine A, Popik V, Tsourkas A (2013) Effect of ligand density, receptor density, and nanoparticle size on cell targeting. Nanomedicine 9:194–201Google Scholar
  97. 97.
    Kawano K, Maitani Y (2011) Effects of polyethylene glycol spacer length and ligand density on folate receptor targeting of liposomal Doxorubicin in vitro. J Drug Deliv 2011:160967PubMedCentralPubMedGoogle Scholar
  98. 98.
    Fakhari A, Baoum A, Siahaan TJ, Le KB, Berkland C (2011) Controlling ligand surface density optimizes nanoparticle binding to ICAM-1. J Pharm Sci 100:1045–1056PubMedGoogle Scholar
  99. 99.
    Yuan H, Li J, Bao G, Zhang S (2010) Variable nanoparticle-cell adhesion strength regulates cellular uptake. Phys Rev Lett 105:138101PubMedGoogle Scholar
  100. 100.
    Fonge H, Huang H, Scollard D, Reilly RM, Allen C (2012) Influence of formulation variables on the biodistribution of multifunctional block copolymer micelles. J Control Release 157:366–374PubMedGoogle Scholar
  101. 101.
    Lemmon MA, Schlessinger J (1994) Regulation of signal transduction and signal diversity by receptor oligomerization. Trends Biochem Sci 19:459–463PubMedGoogle Scholar
  102. 102.
    Laginha K, Mumbengegwi D, Allen T (2005) Liposomes targeted via two different antibodies: assay, B-cell binding and cytotoxicity. Biochim Biophys Acta 1711:25–32PubMedGoogle Scholar
  103. 103.
    Saul JM, Annapragada AV, Bellamkonda RV (2006) A dual-ligand approach for enhancing targeting selectivity of therapeutic nanocarriers. J Control Release 114:277–287PubMedGoogle Scholar
  104. 104.
    Meng S, Su B, Li W et al (2010) Enhanced antitumor effect of novel dual-targeted paclitaxel liposomes. Nanotechnology 21:415103PubMedGoogle Scholar
  105. 105.
    Willmann JK, Lutz AM, Paulmurugan R et al (2008) Dual-targeted contrast agent for US assessment of tumor angiogenesis in vivo. Radiology 248:936–944PubMedGoogle Scholar
  106. 106.
    Kluza E, van der Schaft DW, Hautvast PA et al (2010) Synergistic targeting of alphavbeta3 integrin and galectin-1 with heteromultivalent paramagnetic liposomes for combined MR imaging and treatment of angiogenesis. Nano Lett 10:52–58PubMedGoogle Scholar
  107. 107.
    Kluza E, Jacobs I, Hectors SJ et al (2012) Dual-targeting of alphavbeta3 and galectin-1 improves the specificity of paramagnetic/fluorescent liposomes to tumor endothelium in vivo. J Control Release 158:207–214PubMedGoogle Scholar
  108. 108.
    Zhou H, Jiao P, Yang L, Li X, Yan B (2011) Enhancing cell recognition by scrutinizing cell surfaces with a nanoparticle array. J Am Chem Soc 133:680–682PubMedGoogle Scholar
  109. 109.
    Schlessinger J (2002) Ligand-induced, receptor-mediated dimerization and activation of EGF receptor. Cell 110:669–672PubMedGoogle Scholar
  110. 110.
    Haber DA, Gray NS, Baselga J (2011) The evolving war on cancer. Cell 145:19–24PubMedGoogle Scholar
  111. 111.
    Vanneman M, Dranoff G (2012) Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer 12:237–251PubMedGoogle Scholar
  112. 112.
    Conte P, Guarneri V (2012) The next generation of biologic agents: therapeutic role in relation to existing therapies in metastatic breast cancer. Clin Breast Cancer 12:157–166PubMedGoogle Scholar
  113. 113.
    Jain RK, Duda DG, Clark JW, Loeffler JS (2006) Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Nat Clin Pract Oncol 3:24–40PubMedGoogle Scholar
  114. 114.
    Wolf I, Golan T, Shani A, Aderka D (2010) Cetuximab in metastatic colorectal cancer. Lancet Oncol 11:313–314, author reply 314PubMedGoogle Scholar
  115. 115.
    Vermorken JB, Mesia R, Rivera F et al (2008) Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 359:1116–1127PubMedGoogle Scholar
  116. 116.
    Miller K, Wang M, Gralow J et al (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357:2666–2676PubMedGoogle Scholar
  117. 117.
    Jokerst JV, Gambhir SS (2011) Molecular imaging with theranostic nanoparticles. Acc Chem Res 44:1050–1060PubMedCentralPubMedGoogle Scholar
  118. 118.
    Griffioen AW, van der Schaft DW, Barendsz-Janson AF et al (2001) Anginex, a designed peptide that inhibits angiogenesis. Biochem J 354:233–242PubMedGoogle Scholar
  119. 119.
    van der Schaft DW, Dings RP, de Lussanet QG et al (2002) The designer anti-angiogenic peptide anginex targets tumor endothelial cells and inhibits tumor growth in animal models. FASEB J 16:1991–1993PubMedGoogle Scholar
  120. 120.
    Strijkers GJ, Kluza E, Van Tilborg GA et al (2010) Paramagnetic and fluorescent liposomes for target-specific imaging and therapy of tumor angiogenesis. Angiogenesis 13:161–173PubMedCentralPubMedGoogle Scholar
  121. 121.
    Mulder WJ, Strijkers GJ, Griffioen AW et al (2004) A liposomal system for contrast-enhanced magnetic resonance imaging of molecular targets. Bioconjug Chem 15:799–806PubMedGoogle Scholar
  122. 122.
    Winter PM, Schmieder AH, Caruthers SD et al (2008) Minute dosages of alpha(nu)beta3-targeted fumagillin nanoparticles impair Vx-2 tumor angiogenesis and development in rabbits. FASEB J 22:2758–2767PubMedGoogle Scholar
  123. 123.
    Platta HW, Stenmark H (2011) Endocytosis and signaling. Curr Opin Cell Biol 23:393–403PubMedGoogle Scholar
  124. 124.
    Bareford LM, Swaan PW (2007) Endocytic mechanisms for targeted drug delivery. Adv Drug Deliv Rev 59:748–758PubMedCentralPubMedGoogle Scholar
  125. 125.
    Sapra P, Allen TM (2002) Internalizing antibodies are necessary for improved therapeutic efficacy of antibody-targeted liposomal drugs. Cancer Res 62:7190–7194PubMedGoogle Scholar
  126. 126.
    Miller CR, Bondurant B, McLean SD, McGovern KA, O'Brien DF (1998) Liposome-cell interactions in vitro: effect of liposome surface charge on the binding and endocytosis of conventional and sterically stabilized liposomes. Biochemistry 37:12875–12883PubMedGoogle Scholar
  127. 127.
    Al-Batran SE, Guntner M, Pauligk C et al (2010) Anthracycline rechallenge using pegylated liposomal doxorubicin in patients with metastatic breast cancer: a pooled analysis using individual data from four prospective trials. Br J Cancer 103:1518–1523PubMedCentralPubMedGoogle Scholar
  128. 128.
    Gabizon A, Shmeeda H, Grenader T (2012) Pharmacological basis of pegylated liposomal doxorubicin: impact on cancer therapy. Eur J Pharm Sci 45:388–398PubMedGoogle Scholar
  129. 129.
    Oliveira S, Storm G, Schiffelers RM (2006) Targeted delivery of siRNA. J Biomed Biotechnol 2006:63675PubMedCentralPubMedGoogle Scholar
  130. 130.
    Ma Z, Li J, He F, Wilson A, Pitt B, Li S (2005) Cationic lipids enhance siRNA-mediated interferon response in mice. Biochem Biophys Res Commun 330:755–759PubMedGoogle Scholar
  131. 131.
    Omidi Y, Barar J, Akhtar S (2005) Toxicogenomics of cationic lipid-based vectors for gene therapy: impact of microarray technology. Curr Drug Deliv 2:429–441PubMedGoogle Scholar
  132. 132.
    Schiffelers RM, Ansari A, Xu J et al (2004) Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle. Nucleic Acids Res 32:e149PubMedCentralPubMedGoogle Scholar
  133. 133.
    Kelly C, Jefferies C, Cryan SA (2011) Targeted liposomal drug delivery to monocytes and macrophages. J Drug Deliv 2011:727241PubMedCentralPubMedGoogle Scholar
  134. 134.
    Gao H, Shi W, Freund LB (2005) Mechanics of receptor-mediated endocytosis. Proc Natl Acad Sci USA 102:9469–9474PubMedGoogle Scholar
  135. 135.
    Zhang S, Li J, Lykotrafitis G, Bao G, Suresh S (2009) Size-dependent endocytosis of nanoparticles. Adv Mater 21:419–424PubMedCentralPubMedGoogle Scholar
  136. 136.
    Chithrani BD, Ghazani AA, Chan WC (2006) Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett 6:662–668PubMedGoogle Scholar
  137. 137.
    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 7:1542–1550PubMedGoogle Scholar
  138. 138.
    Epstein-Barash H, Gutman D, Markovsky E et al (2010) Physicochemical parameters affecting liposomal bisphosphonates bioactivity for restenosis therapy: internalization, cell inhibition, activation of cytokines and complement, and mechanism of cell death. J Control Release 146:182–195PubMedGoogle Scholar
  139. 139.
    Schiffelers RM, Koning GA, ten Hagen TLM et al (2003) Anti-tumor efficacy of tumor vasculature-targeted liposomal doxorubicin. J Control Release 91:115–122PubMedGoogle Scholar
  140. 140.
    Murphy EA, Majeti BK, Barnes LA et al (2008) Nanoparticle-mediated drug delivery to tumor vasculature suppresses metastasis. Proc Natl Acad Sci USA 105:9343–9348PubMedGoogle Scholar
  141. 141.
    Goren D, Horowitz AT, Tzemach D, Tarshish M, Zalipsky S, Gabizon A (2000) Nuclear delivery of doxorubicin via folate-targeted liposomes with bypass of multidrug-resistance efflux pump. Clin Cancer Res 6:1949–1957PubMedGoogle Scholar
  142. 142.
    Fens MH, Hill KJ, Issa J et al (2008) Liposomal encapsulation enhances the antitumour efficacy of the vascular disrupting agent ZD6126 in murine B16.F10 melanoma. Br J Cancer 99:1256–1264PubMedCentralPubMedGoogle Scholar
  143. 143.
    Huang HW, Chen FY, Lee MT (2004) Molecular mechanism of peptide-induced pores in membranes. Phys Rev Lett 92:198304PubMedGoogle Scholar
  144. 144.
    Pack DW, Putnam D, Langer R (2000) Design of imidazole-containing endosomolytic biopolymers for gene delivery. Biotechnol Bioeng 67:217–223PubMedGoogle Scholar
  145. 145.
    Horth M, Lambrecht B, Khim MC et al (1991) Theoretical and functional analysis of the SIV fusion peptide. EMBO J 10:2747–2755PubMedGoogle Scholar
  146. 146.
    Berg K, Selbo PK, Prasmickaite L et al (1999) Photochemical internalization: a novel technology for delivery of macromolecules into cytosol. Cancer Res 59:1180–1183PubMedGoogle Scholar
  147. 147.
    Mastrobattista E, Koning GA, van Bloois L, Filipe AC, Jiskoot W, Storm G (2002) Functional characterization of an endosome-disruptive peptide and its application in cytosolic delivery of immunoliposome-entrapped proteins. J Biol Chem 277:27135–27143PubMedGoogle Scholar
  148. 148.
    Oliveira S, Fretz MM, Høgset A, Storm G, Schiffelers RM (2007) Photochemical internalization enhances silencing of epidermal growth factor receptor through improved endosomal escape of siRNA. Biochimica et Biophysica Acta (BBA). Biomembranes 1768:1211–1217Google Scholar
  149. 149.
    Terreno E, Geninatti Crich S, Belfiore S et al (2006) Effect of the intracellular localization of a Gd-based imaging probe on the relaxation enhancement of water protons. Magn Reson Med 55:491–497PubMedGoogle Scholar
  150. 150.
    Strijkers GJ, Hak S, Kok MB, Springer CS Jr, Nicolay K (2009) Three-compartment T1 relaxation model for intracellular paramagnetic contrast agents. Magn Reson Med 61:1049–1058PubMedGoogle Scholar
  151. 151.
    Tanimoto A, Oshio K, Suematsu M, Pouliquen D, Stark DD (2001) Relaxation effects of clustered particles. J Magn Reson Imaging 14:72–77PubMedGoogle Scholar
  152. 152.
    Kok MB, de Vries A, Abdurrachim D et al (2011) Quantitative (1)H MRI, (19)F MRI, and (19)F MRS of cell-internalized perfluorocarbon paramagnetic nanoparticles. Contrast Media Mol Imaging 6:19–27PubMedGoogle Scholar
  153. 153.
    de Vries A, Kok MB, Sanders HM, Nicolay K, Strijkers GJ, Grull H (2012) Multimodal liposomes for SPECT/MR imaging as a tool for in situ relaxivity measurements. Contrast Media Mol Imaging 7:68–75PubMedGoogle Scholar
  154. 154.
    Lee H-Y, Li Z, Chen K et al (2008) PET/MRI dual-modality tumor imaging using arginine-glycine-aspartic (RGD)-conjugated radiolabeled iron oxide nanoparticles. J Nucl Med 49:1371–1379PubMedGoogle Scholar
  155. 155.
    Patel D, Kell A, Simard B, Xiang B, Lin HY, Tian G (2011) The cell labeling efficacy, cytotoxicity and relaxivity of copper-activated MRI/PET imaging contrast agents. Biomaterials 32:1167–1176PubMedGoogle Scholar
  156. 156.
    Criscione JM, Dobrucki LW, Zhuang ZW et al (2011) Development and application of a multimodal contrast agent for SPECT/CT hybrid imaging. Bioconjug Chem 22:1784–1792PubMedCentralPubMedGoogle Scholar
  157. 157.
    De Duve C, Gianetto R, Appelmans F, Wattiaux R (1953) Enzymic content of the mitochondria fraction. Nature 172:1143–1144Google Scholar
  158. 158.
    Gianetto R, De Duve C (1955) Tissue fractionation studies. 4. Comparative study of the binding of acid phosphatase, beta-glucuronidase and cathepsin by rat-liver particles. Biochem J 59:433–438PubMedGoogle Scholar
  159. 159.
    Ciechanover A (2005) Intracellular protein degradation: from a vague idea, through the lysosome and the ubiquitin-proteasome system, and onto human diseases and drug targeting (Nobel lecture). Angew Chem Int Ed Engl 44:5944–5967PubMedGoogle Scholar
  160. 160.
    Panyam J, Zhou WZ, Prabha S, Sahoo SK, Labhasetwar V (2002) Rapid endo-lysosomal escape of poly(DL-lactide-co-glycolide) nanoparticles: implications for drug and gene delivery. FASEB J 16:1217–1226PubMedGoogle Scholar
  161. 161.
    Makino K, Ohshima H, Kondo T (1986) Transfer of protons from bulk solution to the surface of poly(L-lactide) microcapsules. J Microencapsul 3:195–202PubMedGoogle Scholar
  162. 162.
    Stolnik S, Garnett MC, Davies MC et al (1995) The colloidal properties of surfactant-free biodegradable nanospheres from poly(−malic acid-co-benzyl malate)s and poly(lactic acid-co-glycolide). Colloids Surf A Physicochem Eng Asp 97:235–245Google Scholar
  163. 163.
    Muro S, Cui X, Gajewski C, Murciano JC, Muzykantov VR, Koval M (2003) Slow intracellular trafficking of catalase nanoparticles targeted to ICAM-1 protects endothelial cells from oxidative stress. Am J Physiol Cell Physiol 285:C1339–C1347PubMedGoogle Scholar
  164. 164.
    Morachis JM, Mahmoud EA, Sankaranarayanan J, Almutairi A (2012) Triggered rapid degradation of nanoparticles for gene delivery. J Drug Deliv 2012:291219PubMedCentralPubMedGoogle Scholar
  165. 165.
    Turk V, Turk B, Turk D (2001) Lysosomal cysteine proteases: facts and opportunities. EMBO J 20:4629–4633PubMedGoogle Scholar
  166. 166.
    Premzl A, Zavasnik-Bergant V, Turk V, Kos J (2003) Intracellular and extracellular cathepsin B facilitate invasion of MCF-10A neoT cells through reconstituted extracellular matrix in vitro. Exp Cell Res 283:206–214PubMedGoogle Scholar
  167. 167.
    Obermajer N, Kocbek P, Repnik U et al (2007) Immunonanoparticles – an effective tool to impair harmful proteolysis in invasive breast tumor cells. FEBS J 274:4416–4427PubMedGoogle Scholar
  168. 168.
    Brady JM, Cutright DE, Miller RA, Barristone GC (1973) Resorption rate, route, route of elimination, and ultrastructure of the implant site of polylactic acid in the abdominal wall of the rat. J Biomed Mater Res 7:155–166PubMedGoogle Scholar
  169. 169.
    Zhai W, He C, Wu L et al (2012) Degradation of hollow mesoporous silica nanoparticles in human umbilical vein endothelial cells. J Biomed Mater Res B Appl Biomater 100:1397–1403PubMedGoogle Scholar
  170. 170.
    Akagi T, Shima F, Akashi M (2011) Intracellular degradation and distribution of protein-encapsulated amphiphilic poly(amino acid) nanoparticles. Biomaterials 32:4959–4967PubMedGoogle Scholar
  171. 171.
    Kok MB, Strijkers GJ, Nicolay K (2011) Dynamic changes in 1H-MR relaxometric properties of cell-internalized paramagnetic liposomes, as studied over a five-day period. Contrast Media Mol Imaging 6:69–76PubMedGoogle Scholar
  172. 172.
    Lunov O, Syrovets T, Rocker C et al (2010) Lysosomal degradation of the carboxydextran shell of coated superparamagnetic iron oxide nanoparticles and the fate of professional phagocytes. Biomaterials 31:9015–9022PubMedGoogle Scholar
  173. 173.
    Wedeking P, Sotak CH, Telser J, Kumar K, Chang CA, Tweedle MF (1992) Quantitative dependence of MR signal intensity on tissue concentration of Gd(HP-DO3A) in the nephrectomized rat. Magn Reson Imaging 10:97–108PubMedGoogle Scholar
  174. 174.
    Franano FN, Edwards WB, Welch MJ, Brechbiel MW, Gansow OA, Duncan JR (1995) Biodistribution and metabolism of targeted and nontargeted protein-chelate-gadolinium complexes: evidence for gadolinium dissociation in vitro and in vivo. Magn Reson Imaging 13:201–214PubMedGoogle Scholar
  175. 175.
    Thakral C, Abraham JL (2009) Gadolinium-induced nephrogenic systemic fibrosis is associated with insoluble Gd deposits in tissues: in vivo transmetallation confirmed by microanalysis. J Cutan Pathol 36:1244–1254PubMedGoogle Scholar
  176. 176.
    Idee JM, Port M, Dencausse A, Lancelot E, Corot C (2009) Involvement of gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: an update. Radiol Clin North Am 47:855–869, viiPubMedGoogle Scholar
  177. 177.
    Wedeking P, Kumar K, Tweedle MF (1992) Dissociation of gadolinium chelates in mice: relationship to chemical characteristics. Magn Reson Imaging 10:641–648PubMedGoogle Scholar
  178. 178.
    Durbin PW, Williams MH, Gee M, Newman RH, Hamilton JG (1956) Metabolism of the lanthanons in the rat. Proc Soc Exp Biol Med 91:78–85PubMedGoogle Scholar
  179. 179.
    Wedeking P, Tweedle M (1988) Comparison of the biodistribution of 153Gd-labeled Gd(DTPA)2-, Gd(DOTA)-, and Gd(acetate)n in mice. Int J Rad Appl Instrum B 15:395–402PubMedGoogle Scholar
  180. 180.
    Idee JM, Port M, Robic C, Medina C, Sabatou M, Corot C (2009) Role of thermodynamic and kinetic parameters in gadolinium chelate stability. J Magn Reson Imaging 30:1249–1258PubMedGoogle Scholar
  181. 181.
    Maeda H, Wu J, Sawa T, Matsumura Y, Hori K (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65:271–284PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ewelina Kluza
    • 1
  • Gustav J. Strijkers
    • 2
  • Regina G. H. Beets-Tan
    • 1
  • Klaas Nicolay
    • 2
  1. 1.Department of RadiologyGROW School for Oncology and Developmental Biology, Maastricht University Medical CenterMaastrichtThe Netherlands
  2. 2.Biomedical NMR, Department of Biomedical EngineeringEindhoven University of TechnologyEindhovenThe Netherlands

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