Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway

Pharmacological Reviews

Volumn 54, Issue 4, 2002, Pages 561-587

  Qian, Zhong Ming ^a   Li, Hongyan ^a   Sun, Hongzhe ^a   Ho, Kwokping ^a  

^a HONG KONG POLYTECHNIC UNIVERSITY   (Hong Kong)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERFERON; ANTISENSE OLIGONUCLEOTIDE; BISMUTH; BRAIN DERIVED NEUROTROPHIC FACTOR; CD71 ANTIGEN; CHLORAMBUCIL; CISPLATIN; DAUNORUBICIN; DNA; DOXORUBICIN; GALLIUM; HFE PROTEIN; INDIUM; INSULIN; IRON; METAL ION; MITOMYCIN C; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY OX 26; NERVE GROWTH FACTOR; NUCLEIC ACID; POLYLYSINE; RICIN A; RUTHENIUM; TITANIUM; TRANSFERRIN; TRANSFERRIN RECEPTOR; TRANSFERRIN RECEPTOR 2; UNCLASSIFIED DRUG; DRUG;

ANIMAL CELL; BLOOD BRAIN BARRIER; BRAIN; CELL TRANSPORT; COMPLEX FORMATION; DRUG CONJUGATION; DRUG DELIVERY SYSTEM; DRUG TRANSPORT; ENDOCYTOSIS; GENE DELIVERY SYSTEM; HUMAN; HUMAN CELL; IRON TRANSPORT; NONHUMAN; NONVIRAL GENE DELIVERY SYSTEM; PRIORITY JOURNAL; PROTEIN ENGINEERING; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN STRUCTURE; REGULATORY MECHANISM; REVIEW; STRUCTURE ANALYSIS; ANIMAL; CHEMISTRY; METABOLISM; PHYSIOLOGY;

ANIMALS; BRAIN; DRUG DELIVERY SYSTEMS; ENDOCYTOSIS; HUMANS; PHARMACEUTICAL PREPARATIONS; RECEPTORS, TRANSFERRIN; TRANSFERRIN;

EID: 0036889760     PISSN: 00316997     EISSN: None     Source Type: Journal    
DOI: 10.1124/pr.54.4.561     Document Type: Review

References (323)

1. Abrams MJ and Murrer BA (1993) Metal compounds in therapy and diagnosis. Science (Wash DC) 261:725-730.
2. Aisen P (1998) Transferrin, the transferrin receptor and the uptake of iron by cells. Metal Ions Biol Syst 35:535-631.
3. Aisen P, Aasa R, and Redfield AG (1969) The chromium, manganese and cobalt complexes of transferrin. J Biol Chem 244:4628-4633.
4. Aisen P, Wessling-Resnick M, and Leibold EA (1999) Iron metabolism. Curr Opin Chem Biol 3:200-206.
5. Ali SA, Joao HC, Hammerschmid F, Eder J, and Steinkasserer A (1999a) Transferrin trojan horses as a rational approach for the biological delivery of therapeutic peptide domains. J Biol Chem 274:24066-24073.
6. Ali SA, Joao HC, Hammerschmid F, Eder J and Steinkasserer A (1999b) An antigenic HIV-1 peptide sequence engineered into the surface structure of transferrin does not elicit an antibody response. FEBS Lett 459:230-232.
7. 103Ru-chloride in tumor-bearing animals and the mechanism for accumulation in tumor and liver. Int J Radiat Appl Instrum Part B 15:133-140.
8. Andrews NC (1999) Disorders of iron metabolism. N Engl J Med 341:1986-1995.
9. Andrews NC (2000) Iron homeostasis: Insights from genetics and animal models. Nature Rev Genet 1:208-217.
10. Baeumert HG and Fasold H (1989) Cross-linking techniques. Methods Enzymol 172:584-609.
11. Baggiolini M, Deduve C, Masson PL, and Heremans JF (1970) Association of lactoferrin with specific granules in rabbit heterophil leukocytes. J Exp Med 131:559-570.
12. Baker E and Morgan EH (1969) The kinetics of the interaction between rabbit transferrin and reticulocytes. Biochemistry 8:1133-1141.
13. Baker EN (1994) Structure and reactivity of transferrins. Adv Inorg Chem 41:389-463.
14. Barabas K, Sizensky JA, and Faulk WP (1991) Evidence in support the plasma membrane as the target for transferrin-ariramycin conjugates in K562 cells. Am J Reprod Immunol 25:120-123.
15. Barabas K, Sizensky JA, and Faulk WP (1992) Transferrin conjugates of adriamycin are cytotoxic without intercalating nuclear-DNA. J Biol Chem 267:9437-9442.
16. Basilion JP, Kennedy MC, Beinert H, Massinople CM, Klausner RD, and Rouault TA (1994) Overexpression of iron-responsive element-binding protein and its analytical characterization as the RNA-binding form, devoid of an iron-sulfur cluster. Arch Biochem Biophys 311:517-522.
17. Beamish MR and Brown EB (1974) Comparison of behavior of In-111 and Fe-59-labeled transferrin on incubation with human and rat reticulocytes. Blood 43:703-711.
18. Beatty EJ, Cox MC, Frenkiel TA, Tam BM, Mason AB, MacGillivray RTA, Sadler PJ, and Woodworth RC (1996) Interlobe communication in 13C-methionine-labeled human transferrin. Biochemistry 35:7635-7642.
19. Bejaoui N, Page M, and Noel C (1991) Cytotoxicity of transferrin-dauorubin conjugates on small cell carcinoma of the lung (SCCL) cell line NCI-H69. Anticancer Res 11:2211-2213.
20. Bennett MJ, Lebrón JA, and Bjorkman PJ (2000) Crystal structure of the hereditary hemochromatosis protein HFE complexed with transferrin receptor. Nature (Lond) 403:46-53.
21. Bërczi A, Barabas K, Sizensky JA, and Faulk WP (1993b) Adriamycin conjugates of human transferrin bind transferrin receptors and kill K562 and HL-60-cells. Arch Biochem Biophys 300:356-363.
22. Bërczi A, Ruthner M, Szüts V, Fritzer M, Schweinzer E, and Goldenberg H (1993a) Influence of conjugation of doxorubicin to transferrin on the iron uptake by K562-cells via receptor-mediated endocytosis. Eur J Biochem 213:427-436.
23. Bernstein LR (1998) inventor. Methods and compositions to inhibit keratinocyte proliferation. US Patent 5,747,482. 1998 May 5.
24. Beyer U, Roth T, Schumacher P, Maier G, Unold A, Frahm AW, Fiebig HH, Unger C, and Kratz F (1998) Synthesis and in vitro efficacy of transferrin conjugates of the anticancer drug chlorambucil. J Med Chem 41:2701-2708.
25. Bhasker CR, Burgiel G, Neupert B, Emery-Goodman A, Kühn L, and May BK (1993) The putative iron-responsive element in the human erythroid 5-aminolevulinate synthase mRNA mediates translational control. J Biol Chem 268:12699-12705.
26. Bickel U, Yoshikawa T, Landaw EM, and Faull KF (1993) Pharmacological effects in vivo in brain by vector-mediated peptide drug delivery. Proc Natl Acad Sci USA 90:2618-2622.
27. Bickel U, Yoshikawa T, and Pardridge WM (2001) Delivery of peptides and proteins through the blood-brain barrier. Adv Drug Deliver Rev 46:247-279.
28. Boado RJ, Tsukamoto H, and Pardridge WM (1998) Drug delivery of antisense molecules to the brain for the treatment of Alzheimer's diseases and cerebral AIDS. J Pharm Sci 87:1308-1315.
29. Bouton C, Chauveau MJ, Lazereg S, and Drapier JC (2002) Recycling of RNA-binding IRP-1 into an aconitase after nitric oxide removal depends on mitochondrial ATP. J Biol Chem May 30; [epub ahead of print]
30. Bradbury MWB (1997) Transport of iron in the blood-brain-cerebrospinal fluid system. J Neurochem 69:443-451.
31. Briand GG and Burford N (1999) Bismuth compounds and preparations with biological or medicinal relevance. Chem Rev 99:2601-2657.
32. Brinkley M (1992) A brief survey of methods for preparing protein conjugates with dyes, hapten and cross-linking agent. Bioconjug Chem 3:2-13.
33. Brown JP, Hewick RH, Hellström I, Hellström KE, Doolittle RF, and Dreyer WJ (1982) Human melanotransferrin antigen p97 is structurally and functionally related to transferrin. Nature (Lond) 296:171-173.
34. Buchegger F, Trowbridge IS, Liu LFS, White S, and Collawn JF (1996) Functional analysis of human/chicken transferrin receptor chimeras indicates that the carboxy-terminal region is important for ligand binding. Eur J Biochem 235:9-17.
35. Bzdega T, Turi T, Wroblewska B, She D, Chung HS, Kim H, and Neale JH (1997) Molecular cloning of a peptidase against N-acetylaspartylglutamate from a rat hippocampal cDNA library. J Neurochem 69:2270-2277.
36. Camaschella C, Roetto A, Call A, Gobbi de M, Garozzo G, Carella M, Majorano N, Totaro A, and Gasparini P (2000) The gene TfR2 is mutated in a new type of haemochromatosis mapping to 7q22. Nat Genet 25:14-15.
37. Casey JL, Hentze MW, Koeller DM, Caughman SW, Rouault TA, Klausner RD, and Harford JB (1988) Iron-responsive elements-regulation RNA sequences that control mRNA and translation. Science (Wash DC) 240:924-928.
38. Cheng PW (1996) Receptor ligand-facilited gene transfer: Enhancement of liposome-mediated gene transfer and expression by transferrin. Hum Gene Ther 7:275-282.
39. Chitambar CR, Matthaeus WG, Antholine WE, Graff K, and Obrien WJ (1988) Inhibition of leukemic HL60 cell-growth by transferrin-gallium - Effects on ribonucleotide reductase and demonstration of drug synergy with hydroxyurea. Blood 72:1930-1936.
40. Chitambar CR, Narasimhan J, Guy J, Sem DS, and Óbrien WJ (1991) Inhibition of ribonucleotide reductase by gallium in murine leukemic L1210 cells. Cancer Res 51:6199-6201.
41. Chitambar CR and Zivkovic Z (1987) Uptake of Ga-67 by human-leukemic cells-demonstration of transferrin receptor-dependent and transferrin-independent mechanisms. Cancer Res 47:3929-3934.
42. Chitambar CR and Zivkovic-Gilgenbach Z (1990) Role of the acidic receptosome in the uptake and retention of Ga-67 by human leukemic HL60 cells. Cancer Res 50:1484-1487.
43. Citro G, Perrotti D, Cucco C, Dagnano I, Sacchi A, Zupi G, and Calabretta B (1992) Inhibition of leukemia-cell proliferation by receptor-mediated uptake of C-myb antisense oligodeoxynucleotides. Proc Natl Acad Sci USA 89:7031-7035.
44. Clarke MJ, Zhu F, and Frasca DR (1999) Non-platinum chemotherapeutic metallopharmaceuticals. Chem Rev 99:2511-2533.
45. Clausen J, Edeling CJ, and Fogh J (1974) Ga-67 binding to human-serum proteins and tumor components. Cancer Res 34:1931-1937.
46. Constable A, Quick S, Gray NK, and Hentze MW (1992) Modulation of the RNA-binding activity of a regulatory protein by iron in vitro - Switching between enzymatic and genetic function. Proc Natl Acad Sci USA 89:4554-4558.
47. Cotten M, Längle-Rouault F, Kirlappos H, Wagner E, Mechtler K, Zenke M, Beug H, and Birnstiel ML (1990) Transferrin polycation-mediated introduction of DNA into human leukemic-cells - Stimulation by agents that affect the survival of transfected DNA or modulate transferrin receptor levels. Proc Natl Acad Sci USA 87:4033-4037.
48. Cotten M, Wagner E, and Birnstiel ML (1993) Receptor-mediated transport of DNA into eukaryotic cells. Method Enzymol 217:618-644.
49. Cotten M, Wagner E, Zatloukal K, Phillips S, Curiel DT, and Birnstiel ML (1992) 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 USA 89:6094-6098.
50. Curiel DT, Agarwal S, Wagner E, and Cotton M (1991) Adenovirus enhancement of transferrin polylysine-mediated gene delivery. Proc Natl Acad Sci USA 88:8850-8854.
51. Dash PD, Read ML, Fisher KD, Howard KA, Wolfert M, Oupicky D, Subr V, Strohalm J, Ulbrich K, and Seymour LW (2000) 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 275:3793-3802.
52. Dautry-Varsat A, Ciechanover A, and Lodish HF (1983) pH and the recycling of transferrin during receptor-mediated endocytosis. Proc Natl Acad Sci USA 80:2258-2262.
53. Davies M, Parry JE, and Sutcliffe RG (1981) Examination of different preparations of human placental plasma membrane for the binding of insulin, transferrin and immunoglobulins. J Reprod Fertil 63:315-324.
54. Dewan JC, Mikami B, Hirose M, and Sacchettini JC (1993) Structural evidence for a pH-sensitive dilysine trigger in the hen ovotransferrin N-lobe - Implications for transferrin iron release. Biochemistry 32:11963-11968.
55. Donovan A, Brownlie A, Zhou Y, Shepard J, Pratt SJ, Moynihan J, Paw BH, Drejer A, Barut B, Zapata A, et al. (2000) Positional cloning of zebrafish ferropotinl identifies a conserved vertebrate iron exporter. Nature (Lond) 403:776-781.
56. Drapier JC, Hirling H, Wietzerbin J, Kaldy P, and Kühn LC (1993) Biosynthesis of nitric-oxide activates iron regulatory factor in macrophages. EMBO J 12:3643-3649.
57. Dubljevic V, Sali A, and Goding JW (1999) A conserved RGD (Arg-Gly-Asp) motif in the transferrin receptor is required for binding to transferrin. Biochem J 341:11-14.
58. Duncan R (1992) Drug-polymer conjugates: Potential for improved chemotherapy. Anti-cancer Drugs 3:175-210.
59. Eavarone DA, Yu X, and Bellamkonda RV (2000) Targeted drug delivery to C6 glioma by transferrin-coupled liposomes. J Biomed Mater Res 51:10-14.
60. Endicott JA and Ling V (1989) The biochemistry of P-glycoprotein-mediated multi-drug resistance. Annu Rev Biochem 58:137-171.
61. Engebraaten O, Hjortland GO, Juell S, Hieschberg H, and Fodstad Ø (2002) Intra-tumoral immunotoxin treatment of human malignant brain tumors in immunodeficient animals. Int J Cancer 97:846-852.
62. Enns CA, Suomalainen HA, Gebhardt JE, Schroder J, and Sussman HH (1982) Human transferrin receptor: Expression of the receptor is assigned to chromosome 3. Proc Natl Acad Sci USA 79:3241-3245.
63. Faber HR, Bland T, Day CL, Norris GE, Tweedie JW, and Baker EN (1996) Altered domain closure and iron binding in transferrin: The crystal structure of the Asp60Ser mutant of the amino-terminal half-molecule of human lactoferrin. J Mol Biol 256:352-363.
64. Faucheux BA, Nillesse N, Damier P, Spik G, Mouatt-Prigent A, Pierce A, Leveugle B, Kubis N, Hauw JJ, Agid Y, et al. (1995) Expression of lactoferrin receptors in increased in the mesencephalon of patients with Parkinson disease. Proc Natl Acad Sci USA 92:9603-9607.
65. Faulk WP, Taylor CG, Yeh CJG, and McIntyre JA (1990) Preliminary clinical study of transferrin-adriamycin conjugate for drug delivery to acute leukemia patients. Mol Biother 2:57-60.
66. Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo R Jr, Ellis MC, Fullan A, et al. (1996) A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13:399-408.
67. Feder JN, Penny DM, Irrinki A, Lee VK, Lebrón JA, Watson N, Tsuchihashi Z, Sigal E, Bjorkman PJ, and Schatzman RC (1998) The hemochromatosis gene product complexes with the transferrin receptor and lower its affinity for ligand binding. Proc Natl Acad Sci USA 95:1472-1477.
68. Feero WG, Li S, Rosenblatt JD, Sirianni N, Morgan JE, Partridge TA, Huang L, and Hoffman EP (1997) Selection and use of ligands for receptor-mediated gene delivery to myogenic cells. Gene Ther 4:664-674.
69. Fisher KD, Ulbrich K, Subr V, Ward CM, Mautner V, Blakey D, and Seymour LW (2000) A versatile system for receptor-mediated gene delivery permits increased entry of DNA into target cells, enhanced delivery to the nucleus and elevated rates of transgene expression. Gene Ther 7:1337-1343.
70. Fleming MD, Romano MA, Su MA, Garrick LM, Garrick MD, and Andrews NC (1998) Nramp2 is mutated in the anemic Belgrade (b) rat: Evidence of a role for Nramp2 in endosomal iron transport. Proc Natl Acad Sci USA 95:1148-1153.
71. Fleming MD, Trenor CC III, Su MA, Foernzler D, Beier DR, Dietrich WF, and Andrews NC (1997) Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene. Nat Genet 16:383-386.
72. Fleming RE, Migas MC, Holden CC, Waheed A, Britton RS, Tomatsu S, Bacon BR, and Sly WS (2000) Transferrin receptor 2: Continued expression in mouse liver in the face of iron overload and in hereditary hemochromatosis. Proc Natl Acad Sci USA 97:2214-2219.
73. Fleming RE and Sly WS (2001) Hepcidin: A putative iron-regulatory hormone relevant to hereditary hemochromatosis and the anemia of chronic disease. Proc Natl Acad Sci USA 98:8160-8162.
74. Fleming RE and Sly WS (2002) Mechanisms of iron accumulation in hereditary hemochromatosis. Annu Rev Physiol 64:663-680.
75. 4Ru]Cl. J Inorg Biochem 83:139-149.
76. Friden PM (1994) Receptor-mediated transport of therapeutics across the blood-brain-barrier. Neurosurgery 35:294-298.
77. Fritzer M, Barabas K, Szüts K, Bërczi A, Szekeres T, Faulk WP, and Goldenberg H (1992) Cytotoxicity of a transferrin-adriamycin conjugate to anthracycline-resistant cell. Int J Cancer 52:619-623.
78. Fritzer M, Szkeres T, Szüts V, Jarayam HN, and Goldenberg H (1996) Cytotoxic effects of a doxorubicin-transferrin conjugate in multidrug-resistant KB cells. Biochem Pharmacol 52:489-493.
79. Fuchs H, Lucken U, Tauber R, Engel A, and Gessner R (1998) Structural model of phospholipid-reconstituted human transferrin receptor derived by electron microscopy. Structure 6:1235-1243.
80. Gardner PR, Raineri I, Epstein LB, and White CW (1995) Superoxide radical and iron modulate aconitase activity in mammalian cells. J Biol Chem 270:13399-13405.
81. Girelli D, Bozzini C, Roetto A, Alberti F, Daraio F, Colombari R, Olivieri O, Corrocher R, and Camaschella C (2002) Clinical and pathologic findings in hemochromatosis type 3 due to a novel mutation in transferrin receptor 2 gene. Gastroenterology 122:1295-1302.
82. Green NM (1990) Avidin and streptavidin. Methods Enzymol 184:51-67.
83. Gross CN, Irrink A, Feder JN, and Enns CA (1998) Co-trafficking of HFE, a nonclassical major histocompatibility complex class I protein, with the transferrin receptor implies a role in intracellular iron regulation. J Biol Chem 273:22068-22074.
84. Grossmann JG, Neu M, Evans RW, Lindley PF, Appel H, and Hasnain SS (1993b) Metal-induced conformational changes in transferrins. J Mol Biol 229:585-590.
85. Grossmann JM, Mason AB, Woodworth RC, Neu M, Lindley PF, and Hasnain SS (1993a) Asp ligand provides the trigger for closure of transferrin molecules - Direct evidence from X-ray-scattering studies of site-specific mutants of the N-terminal half-molecule of human transferrin. J Mol Biol 231:554-558.
86. Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, and Hediger MA (1997) Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature (Lond) 388:482-488.
87. Guo B, Phillips JD, Yu Y, and Leibold EA (1995) Iron regulated the intracellular degradation of iron regulatory protein 2 by the proteasome. J Biol Chem 270:21645-21651.
88. Guo B, Yu Y, and Leibold EA (1994) Iron regulates cytoplasmic levels of a novel iron-responsive element-binding protein without aconitase activity. J Biol Chem 269:24252-24260.
89. Guo M and Sadler PJ (2000) Competitive binding of the anticancer drug titanocene dichloride to N, N-ethylenebis(o-hydroxyphenylglycine) and adenosine triphosphate: A model for TiIV uptake and release by transferrin. J Chem Soc Dalton Trans 1:7-9.
90. IV-transferrin by cancer cells: Understanding the mechanism of action of the anticancer drug titanocene dichloride. Biochemistry 39:10023-10033.
91. Gutierrez JA, Yu J, Rivera S, and Wessling-Resnick M (1997) Functional expression cloning and characterization of SFT, a stimulator of Fe transport. J Cell Biol 139:895-905.
92. Habeshaw JA, Lister TA, Stansfeld AG, and Greaves MF (1983) Correlation of the transferrin receptor expression with histologic class and outcome in non-Hodgkins lymphoma. Lancet 1:498-501.
93. Hagihara H, Walbridge S, Olson AW, Oldfield EH, and Youle RJ (2000) Vascular protection by chloroquine during brain tumor therapy with Tf-CRM107. Cancer Res 60:230-234.
94. Haile DJ, Rouault TA, Tang CK, Chin J, Harford JB, and Klausner RD (1992) Reciprocal control of RNA-binding and aconitase activity in the regulation of the iron-responsive element binding-protein-role of the iron-sulfur cluster. Proc Natl Acad Sci USA 89:7536-7540.
95. Harding MM and Mokdsi G (2000) Antitumour metallocenes: Structure-activity studies and interactions with biomolecules. Curr Med Chem 7:1289-1303.
96. 59Fe uptake by cultured mouse myeloma cells. Cancer Res 37:3634-3638.
97. Harris WR, Chen Y, and Wein K (1994) Equilibrium-constants for the binding of indium (III) to human serum transferrin. Inorg Chem 33:4991-4998.
98. Harris WR and Pecoraro VL (1983) Thermodynamic binding constants for gallium transferrin. Biochemistry 22:292-299.
99. Hatano T, Ohkawa K, and Matsuda M (1993) Cytotoxic effect of the protein-doxorubicin conjugates on the multidrug-resistant human myelogenous leukemia-cell line, K562, in vitro. Tumor Biol 14:288-294.
100. He QY, Mason AB, Tam BM, Macgillivray RTA, and Woodworth RC (1999a) Dual role of Lys206-Lys296 interaction in human transferrin N-lobe: Iron-release trigger and anion-binding site. Biochemistry 38:9704-9711.
101. 13C] methionine NMR and metal-binding studies of recombinant human transferrin N-lobe and five methionine mutants: Conformational changes and increase sensitivity to chloride. Biochem J 344:881-887.
102. Hege KM, Daleke DL, Waldmarm TA, and Matthay KK (1989) Comparison of anti-Tac and anti-transferrin receptor-conjugated liposomes for specific drug delivery to adult T-cell leukemia. Blood 74:2043-2052.
103. Henderson BR and Kühn LC (1995) Differential modulation of the RNA-binding proteins IRP-1 and IRP-2 in response to iron - IRP-2 inactivation requires translation of another protein. J Biol Chem 270:20509-20515.
104. Henderson BR, Seiser C, and Kühn LC (1993) Characterization of a 2nd RNA-binding protein in rodents with specificity for iron-responsive elements. J Biol Chem 268:27327-27334.
105. Hentze MW, Caughman SW, Rouault TA, Barriocanal JG, Dancis A, Harford JB, and Klausner RD (1987) Identification of the iron-responsive element for the translational regulation of human ferritin messenger-RNA. Science (Wash DC) 238:1570-1573.
106. Hentze MW and Kühn LC (1996) Molecular control of vertebrate iron metabolism: mRNA-based regulatory circuits operated by iron, nitric oxide and oxidative stress. Proc Natl Acad Sci USA 93:8175-8182.
107. Ho KP, Xiao DS, Ke Y, and Qian ZM (2001) The decreased activity of cytosolic aconitase in the liver, spleen and bone marrow in the exercised rats. Biochem Biophys Res Commun 282:264-267.
108. Hullo van M, Cremer K, Cornelis R, and Lameire N (2001) In vivo distribution and speciation of [114mIn]InCl3 in the Wistar rat. J Environ Monit 3:86-90.
109. Huwyler J, Cerletti A, Fricker G, Eberle AN, and Drewe J (2002) By-passing of P-glycoprotein using immunoliposomes. J Drug Target 10:73-79.
110. Huwyler J, Wu DF, and Pardridge WM (1996) Brain drug delivery of small molecules using immunoliposomes. Proc Natl Acad Sci USA 93:14164-14169.
111. Iinuma H, Maruyama K, Okinaga K, Sasaki K, Sekine T, Ishida O, Ogiwara N, Johkura K, and Yonemura Y (2002) Intracellular targeting therapy of cisplatin-encapsulated transferrin-polyethylene glycol liposome on peritoneal dissemination of gastric cancer. Int J Cancer 99:130-137.
112. Ilarduya de CT and Düzgünes N (2000) Efficient gene transfer by transferrin lipoplexes in the presence of serum. Biochim Biophy Acta 1463:333-342.
113. Inoue T, Cavanaugh PG, Steck PA, Brunner N, and Nicolson GL (1993) Differences in transferrin response and numbers of transferrin receptors in rat and human mammary carcinoma lines of different metastatic potentials. J Cell Physiol 156:212-217.
114. Iwai K, Drake SK, Wehr NB, Weissman AM, LaVaute T, Minato N, Klausner RD, Levine RL, and Rouault TA (1998) Iron-dependent oxidation, ubiquitination and degradation of iron regulatory protein 2: Implications for degradation of oxidized proteins. Proc Natl Acad Sci USA 95:4924-4928.
115. Iwai K, Klausner RD, and Rouault TA (1995) Requirements for iron-regulated degradation of the RNA binding protein, iron regulatory protein 2. EMBO J 14:5350-5357.
116. Iyer S and Lönnerdal B (1993) Lacteoferrin, lactoferrin receptors and iron-metabolism. Eur J Clin Nutr 47:232-241.
117. Jefferies WA, Brandon MR, Hunt SV, William AF, Gatter KC, and Mason DY (1984) Transferrin receptor on endothelium of brain capillaries. Nature (Lond) 312:162-163.
118. Jeltsch JM and Chambon P (1982) The complete nucleotide of the chicken ovotransferrin messenger-RNA. Eur J Biochem 122:291-295.
119. Jiang DH, Ke Y, Chang YZ, Ho KP, and Qian ZM (2002) Distribution of ferroportin1 protein in different regions of developing rat brain. Dev Neurosci, in press.
120. Jiang DH and Qian ZM (2001) Intestinal iron absorption and relevant diseases: An update. Chin Med J 81:1533-1535.
121. Jing SQ and Trowbridge IS (1987) Identification of the intermolecular disulfide bonds of the human transferrin receptor and its lipid-attachment site. EMBO J 6:327-331.
122. Johnson VG, Wilson D, Greenfield L, and Youle RJ (1988) The role of the diphtheria toxin receptor in cytosol translocation. J Biol Chem 263:1295-1300.
123. 3H]-biotin bound to different avidin analogues. J Drug Target 3:159-165.
124. Kaplan J and Kushner JP (2000) Mining the genome for iron. Nature (Lond) 403:711-713.
125. Kawabata H, Germain RS, Ikezoe T, Tong X, Green EM, Gombart AF, and Koeffler HP (2001a) Regulation of expression of murine transferrin receptor 2. Blood 98:1949-1954.
126. Kawabata H, Germain RS, Vuong PT, Nakamaki T, Said JW, and Koeffler HP (2000) Transferrin receptor 2-alpha supports cell growth both in iron-chelated cultured cells and in vivo. J Biol Chem 275:16618-16625.
127. Kawabata H, Nakamaki T, Ikonomi P, Smith RD, Germain RS, and Koeffler HP (2001b) Expression of transferrin receptor 2 in normal and neoplastic hematopoietic cells. Blood 98:2714-2719.
128. Kawabata H, Yang R, Hirama T, Vuong PT, Kawano E, Gombart AF, and Koeffler HP (1999) Molecular cloning of transferrin receptor 2 - A new member of the transferrin receptor-like family. J Biol Chem 274:20826-20832.
129. Ke Y and Qian ZM (2002) DMT1: A newly discovered mammalian iron transport protein. Prog Biophys Biochem 29:2-6.
130. Keppler BK, Friesen C, Moritz HG, Vongerichten H, and Vogel E (1991) Tumor-inhibiting bis(β-diketonato) metal complexes. Budotitane, cis-diethoxybis (1-phenylbutane-1, 3-dionato) titanium (IV). Struct Bonding 78:97-127.
131. Kircheis R, Schuller S, Brunner S, Ogris M, Heider KH, Zauner W, and Wagner E (1999) Polycation-based DNA complexes for tumor-targeted gene delivery in vivo. J Gene Med 1:111-120.
132. Kircheis R, Wightman L, Kursa M, Ostermann E, and Wagner E (2002) Tumor-targeted gene delivery: An attractive strategy to use highly active effector molecules in cancer treatment. Gene Ther 9:731-735.
133. Kircheis R, Wightman L, Schreiber A, Robitza B, Rossler V, and Wagner E (2001) Polyethylenimine/DNA complexes shielded by transferrin target gene expression to tumors after systemic application. Gene Ther 8:28-40.
134. Klausner RD, Ashwell JV, Van Renswoude J, Harford JB, and Bridges KR (1983) Binding of apotransferrin to K562 cells: Explanation of the transferrin cycle. Proc Natl Acad Sci USA 80:2263-2266.
135. Koeller DM, Casey JL, Gerhardt EM, Chan LN, Klausner RD, and Harford JB (1989) A cytosolic protein binds to structural elements within the iron regulatory region of the transferrin receptor messenger-RNA. Proc Natl Acad Sci USA 86:3574-3578.
136. Kono K, Torikoshi Y, Mitsutomi M, Itoh T, Emi N, Yanagie H, and Takagishi T (2001) Novel gene delivery systems: Complexes of fusigenic polymer-modified liposomes and lipoplexes. Gene Ther 8:5-12.
137. Köpf-Maier P and Köpf H (1967) Non-platinum-group metal antitumor agents - History, current status and perspectives. Chem Rev 87:1137-1152.
138. Kordower JH, Charles V, Bayer R, Bartus RT, Putney S, Walus LR, and Friden PM (1994) Intravenous administration of a transferrin receptor antibody nerve growth-factor conjugate prevents the degeneration of cholinergic striatal neurons in a model of Huntington disease. Proc Natl Acad Sci USA 91:9077-9080.
139. Kornfeld SB, Leonard JE, Mullen MD, and Taelte R (1991) Assessment of ligand effects in intracellular trafficking of ricin A chain using anti-ricin hybridomas. Cancer Res 51:4316-4322.
140. Kovar M, Strohalm J, Ulbrich K, and Rihova B (2002) In vitro and in vivo effect of HPMA copolymer-bound doxorubicin targeted to transferrin receptor of B-cell lymphoma 38C13. J Drug Target 10:23-30.
141. Kratz F and Beyer U (1998b) Serum proteins as drug carriers of anticancer agents. Drug Delivery 5:281-299.
142. Kratz F, Beyer U, Roth T, Tarasova N, Collery P, Lechienault F, Cazabat A, Shcumacher P, Unger C, and Falken U (1998a) Transferrin conjugates of doxorubicin: Synthesis, characterization, cellular uptake and in vitro efficacy. J Pharm Sci 87:338-346.
143. Kratz F, Hartmann M, Keppler BK, and Messori L (1994) The binding-properties of 2 antitumor ruthenium (III) complexes to apotransferrin. J Biol Chem 269:2581-2588.
144. Kratz F, Keppler BK, Hartmann M, Messori L, and Berger MR (1996) Comparison of the antiproliferative activity of two antitumor ruthenium (III) complexes with their apotransferrin and transferrin-bound forms in human colon cancer cell line. Metal-Based Drugs 3:15-23.
145. Kratz F, Roth T, Fichiner I, Schumacher P, Fiebig HH, and Unger C (2000) In vitro and in vivo efficacy of acid-sensitive transferrin and albumin doxorubicin conjugates in a human xenograft panel and in the MDR-MB-435 mamma carcinoma model. J Drug Target 8:305-318.
146. Kupfer JM, Ruan XM, Liu GG, Maltloff J, Forrester J, and Chaux A (1994) High-efficiency gene-transferrin to autologous rabbit jugular-vein grafts using adenovirus-transferrin/polylysine-DNA complexes. Human Gene Ther 5:1437-1443.
147. Kwok JC and Richardson DR (2002) The iron metabolism of neoplastic cells: Alternations that facilitate proliferation?. Crit Rev Oncol-Hematol 42:65-78.
148. Lai BT, Gao JP, and Lanks KW (1998) Mechanism of action and spectrum of cell lines sensitive to a doxorubicin-transferrin conjugate. Cancer Chemother Pharm 41:155-160.
149. Langer R (1998) Drug delivery and targeting. Nature (Lond) 392:s5-10.
150. Larson SM, Rasey JS, Allen DR, and Nelson NJ (1979) Transferrin-mediated uptake of Ga-67 by EMT-6 sarcoma. 1. Studies in tissue-culture. J Nucl Med 20:837-842.
151. Lasic DD and Templeton NS (1996) Liposomes in gene therapy. Adv Drug Delivery Rev 20:221-266.
152. Laske DW, Ilercil O, Akbasak A, Youle RJ, and Oldfield EH (1994) Efficacy of direct intratumoral therapy with targeted protein toxins for solid human gliomas in nude mice. J Neurosurg 80:520-526.
153. Laske DW, Youle RJ, and Oldfield EH (1997) Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors. Nat Med 3:1362-1368.
154. Lawrence CM, Ray S, Babyonshev M, Galluser R, Borhan DW, and Harrison SC (1999) Crystal structure of the ectodomain of human transferrin receptor. Science (Wash DC) 286:779-782.
155. Lebrón JA, Bennett MJ, Vaughn DE, Chirino AJ, Snow PM, Mintier GA, Feder JN, and Bjorkman PJ (1998) Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor. Cell 93:111-123.
156. Lebrón JA, West AP Jr, and Bjorkman PJ (1999) The hemochromatosis protein HFE competes with transferrin for binding to transferrin receptor. J Mol Biol 294:239-245.
157. Leibman A and Aisen P (1979) Distribution of iron between the binding-sites of transferrin in serum - Methods and results in normal human subjects. Blood 53:1058-1065.
158. Leibold EA and Munro HN (1988) Cytoplasmic protein binds in vitro to a highly conserved sequence in the 5-subunit untranslated region of ferritin heavy-subunit and light-subunit mRNAs. Proc Natl Acad Sci USA 85:2171-2175.
159. Leong KW, Mao HQ, Troung-Le VL, Roy K, Walsh SM, and August JT (1998) DNA-polycation nanospheres as non-viral gene delivery vehicles. J Control Rel 53:183-193.
160. Levay PF and Viljoen M (1995) Lactoferrin: A general review. Haematologica 80:252-267.
161. Levy JE, Jin O, Fujiwara Y, Kuo F, and Anews NC (1999) Transferrin receptor is necessary for development of erythrocytes and the nervous system. Nat Genet 21:396-399.
162. 3+) to human serum transferrin. J Biol Chem 271:9483-9489.
163. Li H, Sadler PJ, and Sun H (1996b) Rationalization of the strength of metal binding to human serum transferrin. Eur J Biochem 242:387-393.
164. Li JY, Sugimura K, Boado R, Lee HJ, Zhang C, Duebel S, and Pardridge WM (1999) 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 12:787-796.
165. Liang KW, Hoffman EP, and Huang L (2000) Targeted delivery of plasmid DNA to myogenic cells via transferrin-conjugated peptide nucleic acid. Mol Ther 1:236-243.
166. Liao WP, DeHaven J, Shao J, Chen JX, Rojanasakul Y, Lamm DL, and Ma JKH (1998) Liposomal delivery of alpha-interferon to murine bladder tumor cells via transferrin receptor-mediated endocytosis. Drug Deliv 5:111-118.
167. Lieu PT, Heiskala M, Peterson PA, and Yang Y (2001) The roles of iron in health and disease. Mol Asp Med 22:1-87.
168. Lima de MCP, Simoes S, Pires P, Gaspar R, Slepushkin V, and Düzgünes N (1999) Gene delivery mediated by cationic liposomes: From biophysical aspects to enhancement of transfection. Mol Membr Biol 16:103-109.
169. Lönnerdal B and Iyer S (1995) Lactoferrin-molecular-structure and biological function. Annu Rev Nutr 15:93-110.
170. Lozier JN, Thomospson AR, Hu PC, Read M, Brinkhous KM, High KA, and Curiel DT (1994) Efficient transfection of primary-cells in a canine hemophilia-B model using adenovirus polylysine DNA complexes. Human Gene Ther 5:313-322.
171. Malecki EA, Devenyi AG, Beard JL, and Connor JR (1999) Existing and emerging mechanisms for transport of iron and manganese to the brain. J Neurosci Res 56:113-122.
172. Mao HQ, Roy K, Troung-Le VL, Janes KA, Lin KY, Wang Y, August JT, and Leong KW (2001) Chitosan-DNA nanoparticles as gene carriers: Synthesis, characterization and transfection efficiency. J Control Release 70:399-421.
173. Maruyama K, Ishida O, Takizawa T, and Moribe K (1999) Possibility of active targeting to tumor tissues with liposomes. Adv Drug Delivery Rev 40:89-102.
174. Mason AB, Tam BM, Woodworth RC, Oliver RWA, Green BN, Lin LN, Brandts JF, Savage KJ, Linbeack JA and MacGillivray RTA (1997) Receptor recognition sites reside in both lobes of human serum transferrin. Biochem J 326:77-85.
175. McClelland A, Kühn LC, and Ruddle FH (1984) The human transferrin receptor gene: Genomic organization and the complete primary structure of the receptor deduced from a cDNA sequence. Cell 39:267-274.
176. McKee TD, DeRome ME, Wu GY, and Findeis MA (1994) Preparation of asialooro-somucoid-polylysine conjugates. Bioconjug Chem 5:306-311.
177. McKie AT, Barrow D, Latunde-Dada GO, Rolfs A, Sager G, Mudaly E, Mudaly M, Richardson C, Barlow D, Bomford A, et al. (2001) An iron-regulated ferric reductase associated with the absorption of dietary iron. Science (Wash DC) 291:1755-1759.
178. Means GE and Feeney RE (1990) Chem modifications of proteins: History and applications. Bioconjug Chem 1:2-12.
179. Messori L, Orioli P, Banholzer V, Pais I, and Zatta P (1999) Formation of titanium (IV) transferrin by reaction of human serum apotransferrin with titanium complexes. FEBS Lett 442:157-161.
180. Messori L, Orioli P, Vullo D, Alessio E, and Iengo E (2000) A spectroscopic study of the reaction of NAMI, a novel ruthenium(III) anti-neoplastic complex, with bovine serum albumin. Eur J Biochem 267:1206-1213.
181. Metzboutigue MH, Jollès J, Mauzurier J, Schoenteng F, Legrand D, Montreuil J, and Jollàs P (1984) Human lactotransferrin amino acid sequence and structural comparisons with other transferrins. Eur J Biochem 145:659-676.
182. Mizutani K, Mikami B, and Hirose M (2001) Domain closure mechanism in transferrins: New viewpoints about the hinge structure and motion as deduced from high resolution crystal structures of ovotransferrin N-lobe. J Mol Biol 309:937-947.
183. Moos T and Morgan EH (1998) Evidence for low molecular weight, non-transferrin-bound iron in rat brain and cerebrospinal fluid. J Neurosci Res 54:486-494.
184. Moos T and Morgan EH (2000) Transferrin and transferrin receptor function in brain barrier systems. Cell Mol Neurobiol 20:77-95.
185. Moos T and Morgan EH (2001) Restricted transport of anti-transferrin receptor antibody (OX26) through the blood-brain barrier in the rat. J Neurochem 79:119-129.
186. Moran PL and Seigman PA (1989) Effects of transferrin-indium on cellular proliferation of a human leukemia cell line. Blood 1:4237-4241.
187. Morgan EH (1964) The interaction between rabbit, human and rat transferring and reticulocytes. Brit J Haemat 10:442-452.
188. Morgan EH (1996) Cellular iron processing. J Gastroenterol Hepatol 11:1027-1030.
189. Morgan EH (2001) Mechanisms of iron transport into rat erythroid cells. J Cell Physiol 186:193-200.
190. Morgan EH and Appleton TC (1969) Autoradiographic localization of 125-I-labelled transferrin in rabbit reticulocytes. Nature (Lond) 223:1371-1372.
191. Morgan EH and Laurell CB (1963) Studies on the exchange of iron between transferring and reticulocytes, Br J Haemat 9:471-483.
192. Müllner EW and Kuhn LC (1988) A stem-loop in the 3′ untranslated region mediates iron-dependent regulation of transferrin receptor messenger-RNA stability in the cytoplasma. Cell 53:815-825.
193. Müllner EW, Neupert B, and Kühn LC (1989) A specific messenger-RNA binding-factor regulates the iron-dependent stability of cytoplasmic transferrin receptor messenger-RNA. Cell 58:373-382.
194. Nicolas G, Bennoun M, Devaux I, Beaumont C, Grandchamp B, Kahn A, and Vaulont S (2001) Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci USA 98:8780-8875.
195. Núñez MT, Gaete V, Watkins JA, and Glass J (1990) Mobilization of iron from endocytic vesicles - The effects of acidification and reduction. J Biol Chem 265:6688-6692.
196. Ogris M, Bruuner S, Schuller S, Kircheis R, and Wagner E (1999) PEGylated DNA/transferrin-PEI complexes: Reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery. Gene Ther 6:595-605.
197. Ogris M, Steinlein P, Kursa M, Mechtler K, Kircheis R, and Wagner E (1998) The size of DNA/transferrin-PEI complexes is an important factor for gene expression in cultured cells. Gene Ther 5:1425-1433.
198. Okamoto CT (2002) From genetics to cellular physiology. Focus on "Regulation of transferrin-induced endocytosis by wild-type and C282Y-mutant HFE in transfected HeLa cells". Am J Physiol 282:C971-C972.
199. Omary MB and Trowbridge IS (1981) Biosynthesis of the human serum transferrin receptor in cultured-cells. J Biol Chem 256:2888-2892.
200. Oshiro S, Kawahara M, Kuroda Y, Zhang C, Cai Y, Kitajima S, and Shirao M (2000) Glial cells contribute more to iron and aluminum accumulation but are more resistant to oxidative stress than neuronal cells. Biochim Biophys Acta 1502:405-414.
201. Pantopoulos K and Hentze MW (1995) Rapid responses to oxidative stress mediated by iron regulatory protein. EMBO J 14:2917-2924.
202. Pantopoulos K and Hentze MW (1998) Activation of iron regulatory protein-1 by oxidative stress in vitro. Proc Natl Acad Sci USA 95:10559-10563.
203. Pantopoulos K, Mueller S, Atzberger A, Ansorge W, Stremmel W, and Hentze MW (1997) Differences in the regulation of iron regulatory protein-1 (IRP-1) by extra- and intracellular oxidative stress. J Biol Chem 272:9802-9808.
204. Pantopoulos K, Weiss G, and Hentze MW (1996) Nitric oxide and oxidative stress (H2O2) control mammalian iron metabolism by different pathways. Mol Cell Biol 16:3781-3788.
205. Pardridge WM (1999) Vector-mediated drug delivery to the brain. Adv Drug Delivery Rev 36:299-321.
206. Pardridge WM, Boado RJ, and Kang YS (1995) Vector-mediated delivery of a polyamide ("peptide") nucleic acid analogue through the blood-brain barrier in vivo. Proc Natl Acad Sci USA 92:5592-5596.
207. Pardridge WM, Buciak JL, and Friden P (1991) Selective transport of an antitransferrin receptor antibody through the blood-brain barrier in vivo. J Pharmacol Exp Ther 259:66-70.
208. Pardridge WM, Wu D, and Sakane T (1998) Combined use of carboxy-directed protein pegylation and vector-mediated blood-brain barrier drug delivery system optimized brain uptake of brain-derived neurotrophic factor following intravenous administration. Pharm Res (NY) 15:576-582.
209. Parkkila S, Waheed A, Britton R, Bacon BR, Zhou XY, Tomatsu S, Fleming RE, and Sly WS (1997) Association of the transferrin receptor in human placenta with HFE, the protein defective in hereditary hemochromatosis. Proc Natl Acad Sci USA 94:13198-13202.
210. Paterson S, Armstrong NJ, Iacopetta BJ, McArdle HJ, and Morgan EH (1984) Intravesicular pH and iron uptake by immature erythroid cells. J Cell Physiol 120:225-232.
211. Penichet ML, Kang YS, Pardridge WM, Morrison SL, and Shin SU (1999) An antibody-avidin fusion protein specific for the transferrin receptor serves as a delivery vehicle for effective brain targeting: Initial applications in anti-HIV antisense drug delivery to the brain. J Immunol 163:4421-4426.
212. Pietrangelo A (2002) Physiology of iron transport and the hemochromatosis gene. Am J Physiol 282:G403-G414.
213. Pirollo KF, Xu L, and Chang EH (2000) Nor-viral gene delivery for p53. Curr Opin Mol Ther 2:168-175.
214. Podbilewicz B and Mellman I (1990) ATP and cytosol requirements for transferrin recycling in intact and disrupted MDCK cells. EMBO J 9:3477-3481.
215. Qian ZM (2002) Nitric oxide and changes of iron metabolism in exercise. Biol Rev, in press.
216. Qian ZM and Ke Y (2001) Rethinking the role of ceruloplasmin in brain iron metabolism. Brain Res Rev 35:287-294.
217. Qian ZM, Liao QK, To Y, Ke Y, Tsoi YK, Wang GF, and Ko KP (2000) Transferrin-bound and transferrin-free iron uptake by the cultured brain astrocytes. Cell Mol Biol 46:541-548.
218. Qian ZM, Pu YM, Tang PL, and Wang Q (1998) Transferrin-bound iron uptake by the cultured cerebellar granule cells. Neurosci Lett 251:9-12.
219. Qian ZM and Shen X (2001) Brain iron transport and neurodegeneration. Trend Mol Med 7:103-108.
220. Qian ZM and Tang PL (1995) Mechanism of iron uptake by mammalian cells. Biochim Biophys Acta 1269:205-214.
221. Qian ZM, Tang PL, and Wang Q (1997b) Iron crosses the endosomal membrane by a carrier-mediated process. Prog Biophys Mol Biol 67:1-15.
222. Qian ZM, To Y, and Feng YM (1999a) Transferrin receptor on the plasma membrane of cultured rat astrocytes. Exp Brain Res 129:473-476.
223. Qian ZM and Wang Q (1998) Expression of iron transport proteins and excessive iron accumulation of iron in the brain in neurodegenerative disorders. Brain Res Rev 27:257-267.
224. Qian ZM, Wang Q, and Pu YM (1997a) Brain iron and neurological disorders. Chin Med J 110:455-458.
225. Qian ZM, Xiao DS, Ke Y, and Liao QK (2001) The increased nitric oxide is one of the causes for the changes in iron metabolism in the exercised rats. Am J Physiol 280:R739-R743.
226. Qian ZM, Xiao DS, Tang PL, Yao FYD, and Liao QK (1999b) The increased expression of transferrin receptor on the membrane of erythroblast in strenuous exercised rats. J Appl Physiol 87:523-529.
227. Raijmakers PGHM, Groeneveld ABJ, Hollander den W, and Teule GJJ (1992) Transport of Ga-67 and In-111 across a membrane - Role of plasma-binding and concentration gradients. Nucl Med Commun 13:349-356.
228. Ramalingam TS, West AP Jr, Lebrón JA, Nangiana JS, Hogn TH, Enns CA, and Bjorkman PJ (2000) Binding to the transferrin receptor is required for endocytosis of HFE and regulation for iron homeostasis. Natl Cell Biol 2:953-957.
229. Rao K, Harford JB, Rouault TA, McClelland A, Ruddle FH, and Klausner RD (1986) Transcriptional regulation by iron of the gene for the transferrin receptor. Mol Cell Biol 6:236-240.
230. Richardson DR and Ponka P (1997) The molecular mechanisms of the metabolism and transport of iron in normal and neoplastic cells. Biochim Biophys Acta 1333:1-40.
231. Roetto A, Totaro A, Piperno A, Piga A, Longo F, Garozzo G, Cail A, Gobbi de M, Gasparini P and Camaschella C (2001) New mutations inactivating transferrin receptor 2 in hemochromatosis type 3. Blood 97:2555-2560.
232. Rose TM, Plowman GD, Teplow DB, Dreyer WJ, Hellström KE, and Brown JP (1986) Primary structure of human melanoma-associated antigen p97 (melanotransferrin) deduced from the mRNA sequence. Proc Natl Acad Sci USA 83:1261-1265.
233. Rouault T and Klausner R (1997) Regulation of iron metabolism in eukaryotes. Curr Topics Cell Regulation 35:1-19.
234. Rouault TA (2001) Systemic iron metabolism: A review and implications for brain iron metabolism. Pediatr Neurol 25:130-137.
235. Roy CN, Penny DM, Feder JN, and Enns CA (1999) The hereditary hemochromatosis protein, HFE, specifically regulates transferrin-mediated iron uptake in HeLa cells. J Biol Chem 274:9022-9028.
236. Ruthner M, Bërczi A, and Goldenberg H (1994) Interaction of a doxorubicintransferrin conjugate with isolated transferrin receptors. Life Sci 54:35-40.
237. Rutledge EA and Enns CA (1996) Cleavage of the transferrin receptor is influenced by the composition of the O-linked carbohydrate at position 104. J Cell Physiol 168:284-293.
238. Sadler PJ, Li H, and Sun H (1999) Coordination chemistry of metals in medicine: Target sites for bismuth. Coord Chem Rev 185-186:689-709.
239. Salter-Cid L, Brunmark A, Li Y, Leturcq D, Peterson PA, Jackson MR, and Yang Y (1999) Transferrin receptor is negatively modulated by the hemochromatosis protein HFE: Implications for cellular homeostasis. Proc Natl Acad Sci USA 96:5434-5439.
240. Sarti P, Ginobbi P, D'Agostino I, Arancia G, Lendaro E, Molinari A, Ippoliti R, and Citro G (1996) Liposomal targeting of leukaemia HL60 cells induced by transferrin-receptor endocytosis. Biotech Appl Biochem 24:269-276.
241. Sato Y, Yamauchi N, Takahashi M, Sasaki K, Fukaura J, Neda H, Fujii S, Hirayama M, Itoh Y, Koshita Y, et al. (2000) In vivo gene delivery to tumor cells by transferrin-streptavidin-DNA conjugate. FASEB J 14:2108-2118.
242. Savigni DL and Morgan EH (1998) Transport mechanisms for iron and other transition metals in rat and rabbit erythroid cells. J Physiol 508:837-850.
243. Schmid S and Smythe E (1991) Stage-specific assays for coated pit formation and coated vesicle budding in vitro. J Cell Biol 114:869-880.
244. Schneider C, Owen MJ, Banville D, and Williams JG (1984) Primary structure of human transferrin receptor deduced from the mRNA sequence. Nature (Lond) 311:675-679.
245. Schneider C, Sutherland R, Newman R, and Greaves M (1982) Structural features of the cell-surface for transferrin that is recognised by the monoclonal antibody-OKT9. J Biol Chem 257:8516-8522.
246. Schnierle BS and Groner B (1996) Retroviral targeted delivery. Gene Ther 3:1069-1073.
247. Schoeman R, Joubert D, Artatti M, and Hawtrey AO (1995) 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 2:509-516.
248. Schryvers AB, Bonnah R, Yu RH, Wong H, and Retzer M (1998) Bacterial lactoferrin receptors. Adv Exp Med Biol 433:123-133.
249. Schwake L, Henkel AW, Riedel HD, Schlenker T, Both M, Migala A, Hadaschik B, Henfling N, and Stremmel W (2002) Regulation of transferrin-induced endocytosis by wide-type and C282Y-mutant HFE in transfected HeLa cells. Am J Physiol Cell Physiol 282:C973-C979.
250. Seki M, Iwakawa J, Cheng H, and Cheng PW (2002) p53 and PTEN/MMAC1/TEP1 gene therapy of human prostate PC-3 carcinoma xenograft, using transferrin-facilitated lipofection gene delivery strategy. Hum Gene Ther 13:761-773.
251. Seligman P (1983) Structure and function of the transferrin receptor. Prog Hematol 13:131-147.
252. Shi N, Boado RJ, and Pardridge WM (2000) Antisense imaging of gene expression in the brain in vivo. Proc Natl Acad Sci USA 97:14709-14714.
253. Shi N and Pardridge WM (2000) Noninvasive gene targeting to the brain. Proc Natl Acad Sci USA 97:7576-7572.
254. Shin SU, Friden P, Moran M, Olson T, and Kang YS (1995) Transferrin-antibody fusion proteins are effective in brain targeting. Proc Natl Acad Sci USA 92:2820-2824.
255. Shin SU, Wu D, Ramanathan R, Pardridge WM, and Morrison SL (1997) Functional and pharmacokinetic properties of antibody/avidin fusion proteins. J Immunol 158:4797-4804.
256. Shongwe MS, Smith CA, Ainscough EW, Baker HM, Brodie AM, and Baker EN (1992) Anion binding by human lactoferrin: Results from crystallographic and physiochemical studies. Biochemistry 31:4451-4458.
257. Simões S, Pires P, Düzgünes M, and Pedroso de MC (1999) Cationic liposomes as gene transfer vectors: Barriers to successful application in gene therapy. Curr Opin Mol Therapeut 1:147-157.
258. Simões S, Slepushkin V, Gaspar R, Pedroso de MC, and Düzgünes N (1998) Gene delivery by negatively charged ternary complexes of DNA, cationic liposomes and transferrin or fusigenic peptides. Gene Ther 5:955-964.
259. Singh M (1999) Transferrin as a targeting ligand for liposomes and anticancer drugs. Curr Pharm Des 5:443-451.
260. Singh M, Atwal H, and Micetich R (1998) Transferrin directed of adriamycin to human cells. Anticancer Res 18:1423-1428.
261. Sizensky JA, Barabas K, and Faulk WP (1992) Characterization of the anti-cancer activity of transferrin-adriamycin conjugates. Am J Reprod Immunol 27:163-166.
262. Smith CA, Sutherland-Smith AJ, Keppler BK, Kratz F, and Baker EN (1996) Binding of ruthenium(III) anti-tumor drugs to human lactoferrin probed by high resolution X-ray crystallographic structure analyses. J Biol Inorg Chem 1:424-443.
263. Smith MA, Harris PLR, Sayre LM, and Perry G (1997) Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proc Natl Acad Sci USA 94:9866-9868.
264. Sohn MH, Jones BJ, Whiting JH, Datz FL, Lynch RE, and Morton KA (1993) Distribution of Ga-67 in normal and hypotransferrinemic tumor-bearing mice. J Nucl Med 34:2135-2143.
265. 97Ru-transferrin uptake in tumor and abscess. Eur J Nucl Med 8:491-494.
266. Srivastava SC, Mausner LF, and Clarke MJ (1989) Ruthenium and Other Nonplatinum Metal Complexes in Cancer Chemotherapy (Clarke MJ ed), Springer-Verlag, Heidelberg.
267. St'astný M, Strohalm J, Plocová D, Ulbrich K, and Ríhová B (1999) A possibility to overcome P-glycoprotein (PGP)-mediated multidrug resistance by antibody-targeted drug conjugated to N-2(2-hydroxypropyl)methacrylamide (HPMA) copolymer. Eur J Cancer 35:459-466.
268. 13C] NMR determination of the order of lobe loading of human transferrin with iron: Comparison with other metal ions. FEBS Lett 422:315-320.
269. Sun H, Cox MC, Li H, and Sadler PJ (1997a) Rationalisation of metal binding to transferrin: Prediction of metal-protein stability constants. Struct Bonding 88:71-102.
270. Sun H, Li H, Mason AB, Woodworth RC, and Sadler PJ (2001) Competitive binding of bismuth to transferrin and albumin in aqueous solution and in blood plasma. J Biol Chem 276:8829-8835.
271. Sun H, Li H, and Sadler PJ (1997b) Biological and medicinal chemistry of bismuth. Chem Ber/Recueil 130:669-681.
272. Sun H, Li H, and Sadler PJ (1999) Transferrin as a metal ion mediator. Chem Rev 99:2817-2842.
273. VI-protein complex: Potential relevance to anticancer activity of titanocenes. Angew Chem Int Ed 37:1577-1579.
274. Sun H and Sadler PJ (1998) Bismuth antiulcer complexes. Topics Biol Inorg Chem 2:159-184.
275. Sun H, Sun EE, Crane FL, Morré DJ, and Faulk WP (1992) Inhibition of transplasma membrane electron transport by transferrin-adriamycin conjugates. Biochim Biophys Acta 1105:84-88.
276. Tabuchi M, Yoshimori T, Yamaguchi K, Yoshida T, and Kishi F (2000) Human NRAMP2/DMT1, which mediates iron transport across endosomal membranes, is localized to late endosomes and lysosomes in HEp-2 cells. J Biol Chem 275:22220-22228.
277. Tanaka T, Fujishima Y, and Kaneo Y (2001) Receptor mediated endocytosis and cytotoxicity of transferrin-mitomycin C conjugate in the HepG2 cell and primary cultured rat hepatocyte. Biol Pharm Bull 24:268-273.
278. Tanaka T, Kaneo Y, and Miyashita M (1996) Synthesis of transferrin-mitomycin C conjugate as a receptor-mediated drug targeting system. Biol Pharm Bull 19:774-777.
279. Tanaka T, Kaneo Y, and Miyashita M (1998) Intracellular disposition and cytotoxicity of transferrin mitomycin C conjugate in HL60 cells as a receptor-mediated drug targeting system. Biol Pharm Bull 21:147-152.
280. Townsend A and Drakesmith H (2002) Role of HFE in iron metabolism, hereditary haemochromatosis anaemia of chronic disease and secondary iron overload. Lancet 359:786-790.
281. Trinder D, Olynyk JK, Sly WS, and Morgan EH (2002) Iron uptake from plasma transferrin by the duodenum is impaired in the Hfe knockout mouse. Proc Natl Acad Sci USA 99:5622-5626.
282. Truong-Le VL, August JT, and Leong KW (1998) Controlled gene delivery by DNA-gelation nanoparticles. Hum Gene Ther 9:1709-1717.
283. Tsan MF, Scheffel U, Tzen KY, and Camargo EE (1980) Factors affecting the binding of Ga-67 in serum. Int J Nucl Med Biol 7:270-273.
284. Tsuchiya Y, Nakao A, Komatsu T, Yamamoto M, and Shimakata K (1992) Relationship between Ga-67-citrate scanning and transferrin receptor expression in lung-diseases. Chest 102:530-534.
285. Uike H, Sakaakibara R, Iwanaga K, Ide M, and Ishiguro M (1998) Efficiency of targeted gene delivery of ligand-poly-L-lysine hybrids with different crosslinks. Biosci Biotech Biochem 62:1247-1248.
286. Vallabhajosula SR, Harwig JF, and Wolf W (1981) The mechanism of tumor localization of gallium-67 citrate: Role of transferrin binding and effect of tumor pH. Int J Nucl Med Biol 8:363-370.
287. Vulpe CD, Kuo YM, Murphy TL, Cowley L, Askwith C, Libina N, and Gitschier N (1999) Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat Genet 21:195-199.
288. Vyas SP and Sihorkar V (2000) Endogenous carriers and ligands in non-immunogenic site-specific drug delivery. Adv Drug Delivery Rev 43:101-164.
289. Vyas SP, Singh A, and Sihorkar V (2001) Ligand-receptor-mediated drug delivery: An emerging paradigm in cellular drug targeting. Crit Rev Ther Drug Carrier Syst 18:1-76.
290. Wagner E, Cotton M, Foisener R, and Birnstiel ML (1991) Transferrin-polycation-DNA complexes: The effect of polycations on the structure of the complex and DNA delivery to cells. Proc Natl Acad Sci USA 88:4255-4259.
291. Wagner E, Zatloukal K, Cotton M, Kirlappos H, Mechtler K, Curiel DT, and Birnstiel ML (1992) Coupling of adenovirus to transferrin polylysine DNA complexes greatly enhances receptor-mediated gene delivery and expression of transfected genes. Proc Natl Acad Sci USA 89:6099-6103.
292. Wagner E, Zenke M, Cotton M, Beug H, and Birnstiel ML (1990) Transferrin-polycation conjugates as carriers for DNA uptake into cells. Proc Natl Acad Sci USA 87:3410-3414.
293. Waheed A, Grubb JH, Zhou XY, Tomatsu S, Fleming RE, Costaldi ME, Britton RS, Bacon B, and Sly WS (2002) Regulation of transferrin-mediated iron uptake by HFE, the protein defective in hereditary hemochromatosis. Proc Natl Acad Sci USA 99:3117-3122.
294. Waheed A, Parkkila S, Saarnio J, Fleming RE, Zhou XY, Tomatsu S, Britton RS, Bacon BR, and Sly WS (1999) Association of HFE protein with transferrin receptor in crypt enterocytes of human duodenum. Proc Natl Acad Sci USA 96:1579-1584.
295. Wang F, Jiang XP, Yang DC, Elliott RL, and Head JF (2000) Doxorubicin-gallium-transferrin conjugate overcomes multidrug resistance: Evidence for drug accumulation in the nucleus of drug resistant MCF-7/ADR cells. Anticancer Res 20:799-808.
296. Ward SG and Taylor RC (1988) In Metal-based Antitumor Drugs (Gielen MF, ed.) p1. Freund Publishing House Ltd, London.
297. Weiner RE, Avis I, Neumann RD, and Mulshine JL (1996) Transferrin dependence of Ga (NO3)3 inhibition of growth in human-derived small cell lung cancer cells. J Cell Biochem 24:276-287.
298. Wellhöner HH, Neville DM, Srinivasachar K, and Erdmann G (1991) Uptake and concentration of bioactive macromolecules by K562 cells via the transferrin cycle utilizing an acid-labile transferrin conjugate. J Biol Chem 266:4309-4314.
299. West AP, Bennett MJ, Sellers VM, Andrews NC, Enns CA, and Bjorkman PJ (2000) Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE. J Biol Chem 275:38135-38138.
300. West AP, Giannetti AM, Herr AB, Bennett MJ, Nangiana JS, Pierce JR, Weiner LP, Snow PM, and Bjorkman PJ (2001) Mutational analysis of the transferrin receptor reveals overlapping HFE and transferrin binding sites. J Mol Biol 313:385-397.
301. Wightman L, Patzelt E, Wagner E, and Kricheis R (1999) Development of transferrin-polycation/DNA based vectors for gene delivery to melanoma cells. J Drug Target 7:293-303.
302. Williams AM and Enns CA (1991) A mutated transferrin receptor lacking asparagine-linked glycosylation sites shows reduced functionality and an association with binding immunoglobulin protein. J Biol Chem 266:17648-17654.
303. Williams J, Elleman TC, Kingston IB, Wilkins AG, and Kuhn KA (1982) The primary structure of hen ovotransferrin. Eur J Biochem 122:297-303.
304. Wu D and Pardridge WM (1999) Neuroprotection with noninvasive neurotrophin delivery to the brain. Proc Natl Acad Sci USA 96:254-259.
305. Wu D, Song BW, Vinters HV, and Pardridge WM (2002) Pharmacokinetics and brain uptake of biotinylated basic fibroblast growth factor conjugated to a blood-brain barrier drug delivery system. J Drug Target 10:239-245.
306. Xia CQ, Wang J, and Shen WC (2000) Hypoglycemic effect of insulin-transferrin conjugate in streptozotocin-induced diabetic rats. J Pharmcol Exp Ther 295:594-600.
307. Xiao DS and Qian ZM (2000) Negative correlation of plasma nitric oxide (NO) and iron levels in the exercised rats. Mol Cell Biochem 208:163-166.
308. Xu L, Frederik P, Pirollo KF, Tang WH, Rait A, Xiang LM, Huang WQ, Cruz I, Yin YZ, and Chang EH (2002) Self-assembly of a virus-mimicking nanostructure system for efficient tumor-targeted gene delivery. Hum Gene Ther 13:469-481.
309. Xu L, Pirollo KF, and Chang EH (2001) Tumor-targeted -p53-gene therapy enhances the efficacy of conventional chemo/radiotherapy. J Control Rel 74:115-128.
310. Xu L, Pirollo KF, Tang WH, Rait A, and Chang EH (1999) Transferrin-liposome-mediated systemic p53 gene therapy in combination with radiation in regression of human head and neck cancer xenografts. Hum Gene Ther 10:2941-2952.
311. Xu LN, Pirollo KF, and Chang EH (1997) Transferrin-liposome-mediated p53 sensitization of squamous cell carcinoma of the head and neck to radiation in vitro. Hum Gene Ther 8:467-475.
312. Yamagata M and Tannock IF (1996) The chronic administration of drugs that inhibit the regulation of intracellular pH: In vitro and anti-tumour effects. Brit J Cancer 73:1328-1334.
313. Yanagihara K, Cheng H, and Cheng PW (2000) Effects of epidermal growth factor, transferrin and insulin on lipofection efficiency in human lung carcinoma cells. Cancer Gene Ther 7:59-65.
314. Yang Y, Nunes FA, Berencsi K, Furth EE, Gonczol E, and Wilson JM (1994) Cellular-immunity to viral-antigens limits E1-deleted adenoviruses for genetherapy. Proc Natl Acad Sci USA 91:4407-4411.
315. Yeh CJG and Faulk WP (1984) Killing of human-tumor cells in culture with adriamycin conjugates of human transferrin. Clin Immunol Immunopathol 32:1-11.
316. Zak O, Ikuta K, and Aisen P (2002) The synergistic anion-binding sites of human transferrin: Chemical and physiological effects of site-directed mutagenesis. Biochemistry 41:7416-7423.
317. Zak O, Trinder D, and Aisen P (1994) Primary receptor-recognition site of human transferrin is in the C-terminal lobe. J Biol Chem 269:7100-7114.
318. Zauner W, Kichler A, Schmidt W, Sinski A, and Wagner E (1996) Glycerol enhancement of ligand-polylysine/DNA transfection. Biotechniques 20:905-913.
319. Zenker M, Steinlei P, Wagner E, Cotton M, Beug H, and Birnstiel ML (1990) Receptor-mediated endocytosis of transferrin polycation conjugates - An efficient way to introduce DNA into hematopoietic-cells. Proc Natl Acad Sci USA 87:3655-3659.
320. III-lactoferrin complex by intestinal cells. Biochemistry 40:13281-13287.
321. Zhang Y and Pardridge WM (2001a) Conjugation of brain-derived neurotrophic factor to a blood-brain barrier drug targeting system enables neuroprotection in regional brain ischemia following intravenous injection of the neurotrophin. Brain Res 889:49-56.
322. Zhang Y and Pardridge WM (2001b) Neuroprotection in transient focal brain ischemia after delayed intravenous administration of brain-derived neurotrophic factor conjugated to a blood-brain barrier drug targeting system. Stroke 32:1378-1384.
323. Zhong W, Parkinson JA, Guo M, and Sadler PJ (2002) Unusual features for zirconium (IV) binding to human serum transferrin. J Biol Inorg Chem 7:589-599.