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Potential of transferrin and transferrin conjugates of liposomes in drug delivery and targeting

  • Review Article
  • Published:
American Journal of Drug Delivery

Abstract

Targeted drug delivery has gained recognition in modern therapeutics and attempts are being made to explore the potential of cell biology-related bioevents in the development of specific and target-oriented systems. In connection to modern therapeutic systems, most of the emphasis has been laid upon the bioconjugated drug delivery systems. Bioconjugates involve the linking of two or more molecules to form a novel complex having the combined properties of its individual components. The nature of the linking agent between the pharmacologic agent and the delivery-augmenting moiety dictates the degree of successful delivery and its outcome. The component for the bioconjugated drug delivery includes receptors and ligands, where the receptors act as molecular targets or portals whereas ligands with receptors provide selective and specific trafficking towards the targeting site. Recently, a number of bioconjugated systems have been discovered for the site-specific presentation and delivery of various bioactive substances using biorelevant ligands, including antibodies, glycoprotein, viral proteins, and molecules of endogenous origin. In this review, the potential of transferrin (Tf) and Tf conjugates of liposomes in site-specific drug delivery systems are discussed. Tf is an abundant component of serum with the capacity to bind and transport iron, while Tf receptor (TfR), a dimeric transmembrane glycoprotein, is present on the surface of the most proliferating, higher eukaryotic cells. Tf expression is also found in nonproliferating tissues, such as hepatocytes, tissue macrophages, pituitary cells, pancreatic islet cells, and the endothelium of brain capillaries. Tumor cells frequently carry elevated numbers of TfRs compared with corresponding normal cells, and reduced serum levels of Tf are often observed in patients with tumors. In the past, various strategies have been developed, which include coupling of the liposomal surface with Tf by using various linking agents. Low-molecular weight drugs and proteins as well as liposomes can be linked with Tf. The Tf-coupled vesicular system is physicochemically stable in the bioenvironment and is site-specific. The aim of coupling liposomes with Tf is to improve the physical and biochemical stability of liposomes and make them appropriate for targeting specific organs and cells. Tf may be widely applied either as a carrier or targeting ligand in the active targeting of anticancer agents, proteins, and genes to primarily proliferating malignant cells that overexpress TfRs. Tf has been used as a molecular conjugate to deliver DNA to erythroleukemic, lung, and liver cell lines. Tf can also be modified with the positive charge N-acylurea groups to make them suitable for electrostatic binding of DNA, in order to achieve a well defined DNA-binding ligand for receptor-mediated gene transfer. Association of Tf with lipoplexes, in particular the negatively charged ternary complexes, significantly overcomes the inhibitory effect of serum and facilitates efficient transfection in many cell lines, including HeLa, K-562 cells, and lung carcinoma cells Calu-3 and H-292 cells. Tf-lipoplex has demonstrated high efficiency in tumor-targeted gene delivery and long-term therapeutic accuracy in systemic p53 gene therapy for both human head and neck cancer and prostate cancer. Tf and Tf-coupled liposomal drug delivery systems may prove particularly valuable to enable the use of a drug that seems to be ineffective or toxic if delivered systematically. The delivery of drugs to the brain has been particularly challenging because of the presence of the blood-brain barrier, which restricts the passage of most therapeutic agents into the brain. Therefore, active targeting of the brain is crucial for effective treatment of brain diseases. The anti-TfR antibody, such as OX26, when coupled with therapeutic agents, has shown potential in drug and gene delivery to the brain.

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References

  1. Tomlinson E. Pathophysiology and the temporal and spatial aspects of drag delivery. In: Tomlinson E, Davis SS, editors. Site specific drag delivery. Chichester: Wiley Int, 1986

    Google Scholar 

  2. Vyas SP, Sihorkar V. Endogenous ligands and carrier in non-immugenic site specific drug delivery. Adv Drag Deliv Rev 2000; 43: 101–64

    Article  CAS  Google Scholar 

  3. Vyas SP, Sihorkar V. Potential of polysaccharide anchored liposomes in drag delivery, targeting, and immunization. J Pharm Pharm Sci 2001; 2: 138–58

    Google Scholar 

  4. Wright S, Huang L. Antibody directed liposomes as drug delivery vehicles. Adv Drag Deliv Rev 1989; 3: 343–89

    Article  Google Scholar 

  5. Yamauchi H, Yano T, Kato T, et al. Effect of sialic acid derivative on long circulating time and tumor concentration of liposomes. Int J Pharmacol 1995; 131: 141–8

    Article  Google Scholar 

  6. Pinnaduwage P, Hunge L. The role of protein-linked oligosaccharides in the bilayer stabilization activity of glycoprotein A for dioleylphosphatidyle ethanolamine liposomes. Biochim Biophys Acta 1989; 986: 106–14

    Article  PubMed  CAS  Google Scholar 

  7. Amselen S, Barnholz Y, Loytor A, et al. Fusion of sendai virus with negatively charge liposomes as studied by pyrene- labeled phospholipids liposomes. Biochim Biophys Acta 1986; 860: 301–13

    Article  Google Scholar 

  8. Kratz F, Beyer U, Roth T, et al. Transferrin conjugates of doxorabicin: synthesis, characterization, cellular uptake, and in vitro efficacy. Cancer Chemother Pharmacol 1998; 41: 155–60

    Google Scholar 

  9. Sun H, Li H, Sadler PJ. Transferrin as a metal ion mediator. Chem Rev 1999; 99: 2817–42

    Article  PubMed  CAS  Google Scholar 

  10. Ehrlich PA. A general review of the recent work in immunity (collected papers of Paul Ehrlich). In Immunity and cancer research, Pergamon press. London, 1956: 456–61

    Google Scholar 

  11. Forssen E, Willis M. Ligand-targeted liposomes. Adv Drag Deliv Rev 1998; 29: 249–71

    Article  CAS  Google Scholar 

  12. Anderson PM, Hanson DC, Hasz DE, et al. Cytokines in liposomes: preliminary studies with IL-1, IL-2, IL-6, GM-CSF and Interferon Gamma. Cytokine 1994; 6: 92–101

    Article  PubMed  CAS  Google Scholar 

  13. Meyer J, Whitcomb L, Collins D. Efficient encapsulation of proteins within liposomes for slow release in vivo. Biochem Biophys Res Commun 1994; 199(2): 433–8

    Article  PubMed  CAS  Google Scholar 

  14. Semple SC, Chonn A, Cullis PR. Interaction of liposomes and lipid based carrier systems with blood proteins: relation to clearance behavior in vivo. Adv Drag Deliv Rev 1998; 32: 3–17

    Article  CAS  Google Scholar 

  15. Qualis MM, Thompson DH. Chloroaluminum phthalocyanine tetrasulfimate delivered via acid labile diplasmenylcholine-folate liposomes: intracellular localization and synergistic phototoxicity. Int J Cancer 2001; 93: 384–92

    Article  Google Scholar 

  16. Reddy JA, Dean D, Kennedy MD, et al. Optimization of folate-conjugated liposomal vectors for folate receptor-mediated gene therapy. J Pharm Sci 1999; 88: 1112–8

    Article  PubMed  CAS  Google Scholar 

  17. Gijsens A, Missiaen L, Merlevede W, et al. Epidermal growth factor-mediated targeting of chlorine C6 selectively potentiates its photodynamic activity. Cancer Res 2000; 60: 2197–202

    PubMed  CAS  Google Scholar 

  18. Renno RZ, Miller JW. Photosensitizer delivery for photodynamic therapy of choroidal neovascularization. Adv Drug Deliv Rev 2001; 52: 63–71

    Article  PubMed  CAS  Google Scholar 

  19. Gijsens A, Derycke A, Missiaen L, et al. Targeting of the photocytotoxic compound AIPcS4 to HeLa cells by transferrin conjugated PEG liposomes. Int J Cancer 2002; 101: 78–85

    Article  PubMed  CAS  Google Scholar 

  20. Opanasopit P, Sakai M, Nishikawa M, et al. Inhibition of liver metastasis by targeting of immunomodulators using mannosulated liposome carrier. J Control Release 2002; 80: 283–94

    Article  PubMed  CAS  Google Scholar 

  21. Mukherjee S, Ghosh RN. Endocytosis. Physiol Rev 1997; 77: 759–803

    PubMed  CAS  Google Scholar 

  22. Fattal E, Patrick C, Dubernet C. ’smart’ delivery of antisense oligonucleotides by anionic pH-sensitive liposomes. Adv Drug Deliv Rev 2004; 56: 931–46

    Article  PubMed  CAS  Google Scholar 

  23. Borhani DW, Harrison SC. Crystallize and X-Ray diffraction study of a soluble form of human transferrin receptor. J Mol Biol 1991; 218: 685–9

    Article  PubMed  CAS  Google Scholar 

  24. Pardridge WM. Blood brain barrier peptide transport and peptide drag delivery to brain. In: Taylor MD, Amidon GL, editors. Peptide based drug design. Washington, DC: American Chemical Society, 1995: 265–96

    Google Scholar 

  25. Langer R. Drag delivery and targeting. Nature 1998; 392: 5–10

    PubMed  CAS  Google Scholar 

  26. Trowbrige IS, Omary MB. Crystallize surface glycoprotein related to cell proliferation of receptor of transferrin. Proc Natl Acad Sci U S A 1991; 72: 3039–42

    Google Scholar 

  27. Huebers HAS, Finch C. The physiology of transferrin and transferrin receptors. Physiol Rev 1989; 67: 520–82

    Google Scholar 

  28. Fishman JB, Handrahan JV, Conner J, et al. Receptor mediated transcytosis of transferrin across the blood brain barrier. J Cell Biol 1987; 101: 423–7

    Google Scholar 

  29. Pardridge WM, Erseberg J, Yang J. Human BBB transferrin receptor. Metabolism 1987; 36: 982–5

    Article  Google Scholar 

  30. Schneider C, Sutherland R, Newman R. Structural feature of the cell surface receptor for transferrin that is recognized by the monoclonal antibodyOKT9. J Biol Chem 1982; 25: 78516–22

    Google Scholar 

  31. Skarlatos S, Yoshikawa J, Pardridge WM. Transport of [125 I] transferrin through the rat blood brain barrier. Brain Res 1995; 683: 164–71

    Article  PubMed  CAS  Google Scholar 

  32. Lawrence CM, Ray S, Babyonshev M, et al. Crystal structure of the ectodomain of human transferrin receptor. Science 1999; 286: 779–82

    Article  PubMed  CAS  Google Scholar 

  33. Fuchs H, Lucken U, Tauber R, et al. Structural model of phospholipid-reconstituted human transferrin receptor derived by electron microscopy. Structure 1988; 6: 1235–43

    Article  Google Scholar 

  34. Cheng Y, Olga Z, Philip A, et al. Structure of human transferrin receptor-transferrin complex. Cell 2004; 116: 565–76

    Article  PubMed  CAS  Google Scholar 

  35. Mason AB, Tam BM, Woodworth RC, et al. Receptor recognition sites reside in both lobes of human serum transferrin. J Biochem 1997; 326: 77–85

    CAS  Google Scholar 

  36. Zak O, Ikuta K, Aisen P. The synergistic anion-binding sites of human transferrin: chemical and physiological effects of site-directed mutagenesis. Biochemistry 2002; 41: 7416–23

    Article  PubMed  CAS  Google Scholar 

  37. Wagner E, Crriel D, Cotton M. Delivery of drug protein and genes into cells using transferrin as a ligand for receptor mediated endocytosis. Adv Drag Deliv Rev 1994; 14: 113–35

    Article  CAS  Google Scholar 

  38. Bradbury MWB. Transport of iron in the blood-brain-cerebrospinal fluid system. J Neurochem 1997; 69: 443–51

    Article  PubMed  CAS  Google Scholar 

  39. Moos T, Morgan EH. Transferrin and transferrin receptor function in brain barrier systems. Cell Mol Neurobiol 2000; 20: 77–95

    Article  PubMed  CAS  Google Scholar 

  40. Griffin T, Raso V. Moninsin in lipid emulsion for the potentiation of ricin A chain immunotoxins. Cancer Res 1991; 53: 4316–22

    Google Scholar 

  41. Johnson VJG, Wilson D, Greenfield L, et al. The role of the diphtheria toxin receptor in cytosol translocation. J Biol Chem 1988; 263: 1295–300

    PubMed  CAS  Google Scholar 

  42. Matthay KK, Abai AM, Cobb S, et al. Role of ligand in antibody-directed endocytosis liposomes by human T-leukaemia cells. Cancer Res 1989; 49: 4879–86

    PubMed  CAS  Google Scholar 

  43. Malecki EA, Devenyi AG, Beard JL, et al. Existing and emerging mechanisms for transport of iron and manganese to the brain. J Neurosci Res 1999; 56: 113–22

    PubMed  CAS  Google Scholar 

  44. Vulpe CD, Kuo YM, Murphy TL, et al. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat Genet 1999; 21: 195–9

    Article  PubMed  CAS  Google Scholar 

  45. Donovan A, Brownlie A, Zhou Y, et al. Positional cloning of zebrafish ferroprotinl identifies a conserved vertebrate iron exporter. Nature 2000; 403: 776–81

    Article  PubMed  CAS  Google Scholar 

  46. Kaplan J, Kushner JP. Mining the genome for iron. Nature 2000; 403: 711–3

    Article  PubMed  CAS  Google Scholar 

  47. Oshiro S, Kawahara M, Kuroda Y, et al. Glial cells contribute more to iron and aluminum accumulation but are more resistant to oxidative stress than neuronal cells. Biochim Biophy Acta 2000; 1502: 405–14

    Article  CAS  Google Scholar 

  48. Kawabata H, Yang R, Hirama T, et al. Molecular cloning of transferrin receptor 2: a new member of the transferrin receptor-like family. J Biol Chem 1999; 274: 20826–32

    Article  PubMed  CAS  Google Scholar 

  49. Kawabata H, Germain RS, Ikezoe T, et al. Regulation of expression of murine transferrin receptor 2. Blood 2001 Sep 15; 98: 1949–54

    Article  PubMed  CAS  Google Scholar 

  50. West AP, Bennett MJ, Sellers VM, et al. Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE. J Biol Chem 2000; 275: 38135–8

    Article  PubMed  CAS  Google Scholar 

  51. Nicolas G, Bennoun M, Devaux I, et al. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci U S A 2001; 98: 8780–875

    Article  PubMed  CAS  Google Scholar 

  52. Fleming RE, Sly WS. Hepcidin: a putative iron-regulatory hormone relevant to hereditary hemochromatosis and the anemia of chronic disease. Proc Natl Acad Sci US A 2001; 98: 8160–2

    Article  CAS  Google Scholar 

  53. Fleming RE, Sly WS. Mechanisms of iron accumulation in hereditary hemochromatosis. Annu Rev Physiol 2002; 64: 663–80

    Article  PubMed  CAS  Google Scholar 

  54. Girelli D, Bozzini C, Roetto A, et al. Clinical and pathologic findings in hemochromatosis type 3 due to a novel mutation in transferrin receptor 2 gene. Gastroenterology 2002; 122: 1295–302

    Article  PubMed  CAS  Google Scholar 

  55. Annelies SLD, Peter AM. Transferrin mediated targeting of hypericin embedded in sterically stabilized PEG-liposomes. Int J Oncol 2002; 20: 181–7

    Google Scholar 

  56. Gabizon A, Martin F. Polyethylene glycone coated (peglated) liposomal Doxorubicin: rationale for use in solid tumors. Drugs 1997; 54: 15–21

    Article  PubMed  CAS  Google Scholar 

  57. Lenei F, Angelini N, Gheui F, et al. Spectroscopic and photocaustic studies of hypercini embedded in liposomes as a photoreceptor model. Photochem Photobiol 1995; 62: 199–204

    Article  Google Scholar 

  58. Bouirig II, Eloy D, Jordon P. Formation of reactive deoxygenage singulet photosensible par hypericine dans des liposomes de dipalmitoulphospha-tidylcholine. Misc en evidence d’une photooxydation rotardee. J Chem Phys 1992; 89: 1391–411

    CAS  Google Scholar 

  59. Losi A. Fluroscence and time resolved photoacoustics of hypericin inserted in liposome: dependence on pigment concentration and bilayer phase. Photochem Photobiol 1997; 65: 791–801

    Article  CAS  Google Scholar 

  60. Moon T, Morgan EH. Evidence for low molecular weight, non-transferrin bound iron in rat brain and cerebrospinal fluid. J Neurosci Res; 54: 486–94

  61. Mesley SW, Johan EVL, Cynthia MA. Targeted photodynamic therapy via receptor mediated delivery systems. Adv Drug Deliv Rev 2004; 56: 53–76

    Article  CAS  Google Scholar 

  62. Sorokin L, Organ EG, Yeoh GCT. Transformation induced changed in transferrin and iron metabolism in myogenic cells. Cancer Res 1989; 49: 1941–7

    PubMed  CAS  Google Scholar 

  63. Bernstein LR, inventor. Methods and compositions to inhibit keratinocyte proliferation. US patent 5: 747,482. 1998 May 5

  64. Clarke MJ, Zhu F, Frasca DR. Non-platinum chemotherapeutic metallopharmaceuticals. Chem Rev 1999; 99: 2511–33

    Article  PubMed  CAS  Google Scholar 

  65. Harding MM, Mokdsi G. Antitumour metallocenes: structure-activity studies and interactions with biomolecules. Curr Med Chem 2000; 7: 1289–303

    Article  PubMed  CAS  Google Scholar 

  66. Chitamber CR, Matthaeus WG, Antholine WE, et al. Inhibition of leukemic HL60 cell growth by transferrin-galium: effect on ribonucleotide reductase and demonstration of drug synergy with hydroxyurea. Blood 1988; 72: 1930–6

    Google Scholar 

  67. Eavarone DA, Yu X, Bellamkonda RV. Targeted drug delivery to C6 glioma by transferrin-coupled liposomes. J Biomed Mater Res 2000; 51: 10–4

    Article  PubMed  CAS  Google Scholar 

  68. Laske DW, Ilercil O, Akbasak A, et al. Efficacy of direct intratumoral therapy with targeted protein toxins for solid human gliomas in nude mice. J Neurosurg 1994; 80: 520–6

    Article  PubMed  CAS  Google Scholar 

  69. Laske DW, Youle RJ, Oldfield EH. Tumor regression with regional distribution of the targeted toxin Tf-CRM107 in patients with malignant brain tumor. Nat Med 1997; 3: 1362–8

    Article  PubMed  CAS  Google Scholar 

  70. Braslawsky GR, Edson M, Pearce W, et al. Antitumor activity of adriamycin (hydrozone linked) immunoconjugates compared with free adriamycin and specificity of tumour cell killing. Cancer Res 1990; 50: 6608–14

    PubMed  CAS  Google Scholar 

  71. Weaver M. Tansferrin receptor ligand-targeted toxin conjugate (Tf-CRM107) for therapy of malignant glioma. J Neurooncol 2003; 65: 3–13

    Article  PubMed  Google Scholar 

  72. Braslawsky GR, Edson M, Kadow K, et al. Adriamycin (hydrozone): antibody conjugates require internalization and intrecellular acid hydrolysis for antitumor activity. Cancer Immunother 1991; 33: 367–74

    Article  CAS  Google Scholar 

  73. Friden PM, Walus L, Taylor M, et al. Drug delivery to the brain using as anti-transferrin receptor antibody. NIDA Res Monogr 1992; 120: 202–17

    PubMed  CAS  Google Scholar 

  74. Crystal RG. Transfer of gene to humans. Science 1995; 270: 404–10

    Article  PubMed  CAS  Google Scholar 

  75. Maruyama K, Takizawa T, Yuda T, et al. Targetability of novel immunoliposomes modified with amphipathic poly(ethylene glycol)s conjugated at their distal terminals to monoclonal antibodies. Biochim Biophys Acta 1995; 1234: 74–80

    Article  PubMed  Google Scholar 

  76. Perkus ME, Limback K, Paolitti E. Cloning and expression of foreign genes in vaccinia virus, using a host range selection system. J Virol 1989; 63: 3829–6

    PubMed  CAS  Google Scholar 

  77. Falkner FG, Moss B. Escherichia coli gpt gene provides dominate of vaccinia virus open reading frame expression vectors. J Virol 1989; 62: 1849–54

    Google Scholar 

  78. Wagner E, Zenke M, Cotton M, et al. Transferrin polycation conjugates as carriers for DNA uptake into cells. Proc Natl Acad Sci U S A 1990; 87: 3410–4

    Article  PubMed  CAS  Google Scholar 

  79. Cotton M, Lnflw O, Uulr F, et al. Transferrin polycation mediated introduction of DNA into human leukemic cells: stimulation by agents that affect the survival of transfected DNA of modulate transferrin receptor levels. Proc Natl Acad Sci USA 1990; 87: 4033–7

    Article  Google Scholar 

  80. Cotten M, Wagner E, Birnstiel ML. Receptor-mediated transport of DNA into eukaryotic cells. Methods Enzymol 1993; 217: 618–44

    Article  PubMed  CAS  Google Scholar 

  81. Citro G, Perrotti D, Cucco C, et al. Inhibition of leukemia-cell proliferation by receptor-mediated uptake of C-myb antisense oligodeoxynucleotides. Proc Natl Acad Sci U S A 1992; 89: 7031–5

    Article  PubMed  CAS  Google Scholar 

  82. Orrantia E, Chang PL. Intracellular distribution of DNA internalised through calcium phosphate precipitation. Cell Res 1990; 190: 170–4

    Article  CAS  Google Scholar 

  83. Zenker M, Steinlei P, Wagner E, et al. Receptor-mediated endocytosis of transferrin polycation conjugates: an efficient way to introduce DNA into hematopoietic-cells. Proc Natl Acad Sci U S A 1990; 87: 3655–9

    Article  Google Scholar 

  84. Molas M, Gómez-Valadés AG, Vidal-Alabró A, et al. Receptor-mediated gene transfer vectors: progress towards genetic Pharmaceuticals. Curr Gene Ther 2003; 3: 468–85

    Article  PubMed  CAS  Google Scholar 

  85. Wiethoff CM, Middaugh CR. Barriers to non viral gene delivery. J Pharm Sci 2003; 92: 203–17

    Article  PubMed  CAS  Google Scholar 

  86. Cotton M, Wagner E, Birnstiel ML, et al. Transferrin polycation DNA complexes: the effect of polycation on the structure of the complex and DNA delivery to cells. Proc Natl Acad Sci U S A 1991; 88: 4255–9

    Article  Google Scholar 

  87. Cain CC, Sipe DM, Murphy RF. Regulation of endocytosic pH by the Na, KATPase of living cells. Proc Natl Acad Sci U S A 1989; 86: 544–8

    Article  PubMed  CAS  Google Scholar 

  88. Cristiano RJ, Smith L, Woo SLC. Hepatic gene delivery and expression in primary hepatocytes. Proc Natl Acad Sci U S A 1993; 90: 2122–6

    Article  PubMed  CAS  Google Scholar 

  89. Gottschalk SC, Cristiano RJ, Smith L, et al. Folate mediated gene delivery and expression in vitro. Cancer Gene Ther 1994; 1: 185–91

    CAS  Google Scholar 

  90. Cristiano RJ, Roth JA. Epidermal growth factor mediated DNA delivery into lung cancer cells via the epidermal growth factor receptor. Cancer Gene Ther 1996; 3: 4–10

    PubMed  CAS  Google Scholar 

  91. Ding ZM, Cristiano RJ, Roth JA, et al. Malaria circumsporozoite protein is a novel gene delivery vehicle to primary hepatocyte cultures and cultured cell. J Biol Chem 1995; 270: 3667–76

    Article  PubMed  CAS  Google Scholar 

  92. Sosnowski BA, Gonzalez AM, Chandler LA, et al. Targeting DNA to cells with basic fibroblast growth factor. J Biol Chem 1996; 271: 33647–53

    Article  PubMed  CAS  Google Scholar 

  93. Kircheis R, Schuller S, Brunner S, et al. Polycation-based DNA complexes for tumor-targeted gene delivery in vivo. J Gene Med 1999; 1: 111–20

    Article  PubMed  CAS  Google Scholar 

  94. Liang KW, Hoffman EP, Huang L. Targeted delivery of plasmid DNA to myogenic cells via transferrin-conjugated peptide nucleic acid. Mol Ther 2000; 1: 236–43

    Article  PubMed  CAS  Google Scholar 

  95. Mullur M, Gissman L, Cristiano RJ, et al. Papillomanirus capsid binding and uptake by cells from different tissues and species. J Virol 1995; 69: 948–54

    Google Scholar 

  96. Wagner E, Plank C, Zatloukal K, et al. Influenza virus gemafflutinin HA-2 N-terminal fusogenic peptides segment gene transfer by transferrin polymydine DNA complexes: toward a synthetic virus like gene transfer vehicle. Proc Natl Acad Sci U S A 1992; 89: 7934–8

    Article  PubMed  CAS  Google Scholar 

  97. Cotton M, Wagner E, Zatloukal K, et al. High-efficiency receptor-mediated delivery of small and large (48 kilobase) gene constructs using the endosome-disruption activity of defective or chemically inactivated adenovirus particles. Proc Natl Acad Sci U S A 1992; 89: 6094–8

    Article  Google Scholar 

  98. Baker A, Cotton M. Delivery of bacterial artificial chromosomes into mammalian cells with psoralen: inactivated adenovirus carrier. Nucleic Acids Res 1991; 25: 226

    Google Scholar 

  99. Aisen P, Listowsky I. Iron transport and storage proteins. Annu Rev Biochem 1980; 49: 357–93

    Article  PubMed  CAS  Google Scholar 

  100. Kircheis R, Wightman L, Schreiber A, et al. Polyethylenimine/DNA complexes shielded by transferrin target gene expression to tumors after systemic application. Gene Ther 2001; 8: 28–40

    Article  PubMed  CAS  Google Scholar 

  101. Wightman L, Patzelt E, Wagner E, et al. Development of transferrin polycation/DNA based vectors for gene delivery to melanoma cells. J Drug Target 1999; 7: 293–303

    Article  PubMed  CAS  Google Scholar 

  102. Dash PD, Read ML, Fisher KD, et al. Decreased binding to proteins and cells of polymeric gene delivery vectors surface modified with a multivalent hydrophilic polymer and retargeting through attachment of transferrin. J Biol Chem 2000; 275: 3793–802

    Article  PubMed  CAS  Google Scholar 

  103. Ogris M, Bruuner S, Schuller S, et al. PEGylated DNA/transferrin-PEI complexes: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery. Gene Ther 1999; 6: 595–605

    Article  PubMed  CAS  Google Scholar 

  104. Wagner E, Cotton M, Foisener R, et al. Transferrin-polycation-DNA complexes: the effect of polycations on the structure of the complex and DNA delivery to cells. Proc Natl Acad Sci U S A 1991; 88: 4255–9

    Article  PubMed  CAS  Google Scholar 

  105. Schoeman R, Joubert D, Artatti M, et al. Further studies on targeted DNA transferrin to cells using a highly efficient delivery system of biotinylated transferrin and biotinylated polylysine complexed to streptavidin. J Drug Target 1995; 2: 509–16

    Article  PubMed  CAS  Google Scholar 

  106. Lasic DD, Templeton NS. Liposomes in gene therapy. Adv Drug Deliv Rev 1996; 20: 221–66

    Article  CAS  Google Scholar 

  107. Wenhao L, Tatsuhiro I, Rieko T, et al. Cell type gene expression, mediated by TFL-3, a cationic liposomal vector, is controlled by a post-transcription process of delivered plasmid DNA. Int J Pharmacol 2004; 276: 67–74

    Article  CAS  Google Scholar 

  108. Pirollo KF, Xu L, Chang EH. Nor-viral gene delivery for p53. Curr Opin Mol Ther 2000; 2: 168–75

    PubMed  CAS  Google Scholar 

  109. Cheng PW. Receptor ligand-facilitated gene transfer: enhancement of liposome mediated gene transfer and expression by transferrin. Hum Gene Ther 1996; 7: 275–82

    Article  PubMed  CAS  Google Scholar 

  110. Simoes S, Slepushkin V, Gaspar R, et al. Gene delivery by negatively charged ternary complexes of DNA, cationic liposomes and transferrin or fusigenic peptides. Gene Ther 1998; 5: 955–64

    Article  PubMed  CAS  Google Scholar 

  111. Tros de Ilarduya C, Duzgunes N. Efficient gene transfer by transferrin lipoplexes in the presence of serum. Biochim Biophys Acta 2000; 1463: 333–42

    Article  PubMed  CAS  Google Scholar 

  112. Yanagihara K, Cheng H, Cheng PW. Effects of epidermal growth factor, transferrin and insulin on lipofection efficiency in human lung carcinoma cells. Cancer Gene Ther 2000; 7: 59–65

    Article  PubMed  CAS  Google Scholar 

  113. Kono K, Torikoshi Y, Mitsutomi M, et al. Novel gene delivery systems: complexes of fusigenic polymer-modified liposomes and lipoplexes. Gene Ther 2001; 8: 5–12

    Article  PubMed  CAS  Google Scholar 

  114. de Lima MC, Simoes S, Pires P, et al. Gene delivery mediated by cationic liposomes: from biophysical aspects to enhancement of transfection. Mol Membr Biol 1999; 16: 103–9

    Article  PubMed  Google Scholar 

  115. Xu L, Pirollo KF, Chang EH. Transferrin-liposome-mediated p53 sensitization of squamous cell carcinoma of the head and neck to radiation in vitro. Hum Gene Ther 1997; 8: 467–75

    Article  PubMed  CAS  Google Scholar 

  116. Xu L, Pirollo KF, Tang WH, et al. Transferrin-liposome mediated systemic p53 gene therapy in combination with radiation in regression of human head and neck cancer xenografts. Hum Gene Ther 1999; 10: 2941–52

    Article  PubMed  CAS  Google Scholar 

  117. Xu L, Pirollo KF, Chang EH. Tumor-targeted p53-gene therapy enhances the efficacy of conventional chemo/radiotherapy. J Control Release 2001; 74: 115–28

    Article  PubMed  CAS  Google Scholar 

  118. Xu L, Frederik P, Pirollo KF, et al. Self-assembly of a virus-mimicking nanostructure system for efficient tumor-targeted gene delivery. Hum Gene Ther 2002; 13: 469–81

    Article  PubMed  CAS  Google Scholar 

  119. Seki M, Iwakawa J, Cheng H, et al. p53 and PTEN/MMAC1/TEP1 gene therapy of human prostate PC-3 carcinoma xenograft, using transferrin facilitated lipofection gene delivery strategy. Hum Gene Ther 2002; 13: 761–73

    Article  PubMed  CAS  Google Scholar 

  120. Yoshikawa T, Pardridge WM. Biotin delivery to the brain with a covalent conjugate momoclonal antibody to the transferrin receptor. J Pharmacol Exp Ther 1992; 263: 896–903

    Google Scholar 

  121. Huwyler H, Wu D, Pardridge WM. Brain drug delivery of small molecules using immunoliposomes. Proc Natl Acad Sci U S A 1996; 93: 14164–9

    Article  PubMed  CAS  Google Scholar 

  122. Li JY, Sugimura K, Boado R. Genetically engineered brain drug delivery vectors: cloning, expression and in vivo application of an anti-transferrin receptor single chain antibody-streptavidin fusion gene and protein. Protein Eng 1999; 12: 787–96

    Article  PubMed  CAS  Google Scholar 

  123. Shi N, Pardridge WM. Noninvasive gene targeting to the brain. Proc Natl Acad Sci USA 2000; 20: 7567–72

    Article  Google Scholar 

  124. Shin SU, Friden P, Moran M, et al. Transferrin-antibody fusion proteins are effective in brain targeting. Proc Natl Acad Sci U S A 1995; 92: 2820–4

    Article  PubMed  CAS  Google Scholar 

  125. Zhang Y, Boado RJ, Pardridge WM. In vivo knockdown of gene expression in brain cancer with intravenous RNAi in adult rats. J Gene Med 2003; 12: 1039–45

    Article  CAS  Google Scholar 

  126. Pardridge WM, Boado RJ, Kang YS. Vector-mediated delivery of a polyamide (“peptide”) nucleic acid analogue through the blood-brain barrier in vivo. Proc Natl Acad Sci U S A 1995; 92: 559–61

    Article  Google Scholar 

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Acknowledgments

The authors are thankful to the Council of Scientific and Industrial Research, New Delhi, India, for providing financial assistance to carry out this project on brain targeting of drugs.

The authors have no conflicts of interest directly relevant to the content of this manuscript.

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  1. Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr H. S. Gour University, Sagar (M.P.), India

    Vandana Soni,  S. K. Jain & D. V. Kohli

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  1. Vandana Soni
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  2. S. K. Jain
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  3. D. V. Kohli
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Correspondence to S. K. Jain.

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Soni, V., Jain, S.K. & Kohli, D.V. Potential of transferrin and transferrin conjugates of liposomes in drug delivery and targeting. Am J Drug Deliv 3, 155–170 (2005). https://doi.org/10.2165/00137696-200503030-00002

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  • DOI: https://doi.org/10.2165/00137696-200503030-00002

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