The significance of transferrin receptors in oncology: The development of functional nano-based drug delivery systems

Current Drug Delivery

Volumn 11, Issue 4, 2014, Pages 427-443

  Tortorella, Stephanie ^a,b   Karagiannis, Tom C ^a,b  

^a BAKER IDI HEART AND DIABETES INSTITUTE   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

Cancer therapy; Nanoparticles; Targeted therapy; Transferrin; Transferrin receptor

Indexed keywords

ANTINEOPLASTIC AGENT; CALAA 01; CONTRAST MEDIUM; MBP 426; NANOCARRIER; SGT 53; SGT 94; TRANSFERRIN NANOPARTICLE; TRANSFERRIN RECEPTOR; UNCLASSIFIED DRUG; NANOMATERIAL; TRANSFERRIN; TUMOR PROTEIN;

BLOOD BRAIN BARRIER; CANCER GENE THERAPY; CANCER RESEARCH; CLINICAL TRIAL (TOPIC); DRUG CONJUGATION; DRUG DELIVERY SYSTEM; HUMAN; MOLECULAR IMAGING; NANOENCAPSULATION; NANOMEDICINE; NANOPHARMACEUTICS; NEOPLASM; NONHUMAN; PRIORITY JOURNAL; REVIEW; ANIMAL; CHEMISTRY; DRUG FORMULATION; METABOLISM; NEOPLASMS;

ANIMALS; ANTINEOPLASTIC AGENTS; DRUG COMPOUNDING; DRUG DELIVERY SYSTEMS; HUMANS; NANOSTRUCTURES; NEOPLASM PROTEINS; NEOPLASMS; RECEPTORS, TRANSFERRIN; TRANSFERRIN;

EID: 84904760738     PISSN: 15672018     EISSN: 18755704     Source Type: Journal    
DOI: 10.2174/1567201810666140106115436     Document Type: Review

References (135)

1. Whitesides, G. M. The 'right' size in nanobiotechnology. Nat. Biotech., 2003, 21 (10), 1161-1165.
2. Jiang, W.; Kim, B. Y. S.; Rutka, J.; Chan, W. C. W. Nanoparticlemediated cellular response is size-dependent. Nat. Nanotechnol., 2008, 3 (3), 145-150.
3. Lynch, I.; Cedervall, T.; Lundqvist, M.; Cabaleiro-Lago, C.; Linse, S.; Dawson, K. A. The nanoparticle-protein complex as a biological entity; a complex fluids and surface science challenge for the 21st century. Adv. Colloid Interface Sci., 2007, 134-135 (0), 167-174.
4. Hamilton, T. A.; Wada, H. G.; Sussman, H. H. Identification of transferrin receptors on the surface of human cultured cells. Proc. Natl. Acad. Sci. U. S. A., 1979, 76 (12), 6406-6410.
5. Galbraith, G. M.; Galbraith, R. M.; Temple, A.; Faulk, W. P. Demonstration of transferrin receptors on human placental trophoblast. Blood, 1980, 55 (2), 240-242.
6. Trowbridge, I. S.; Omary, M. B. Human cell surface glycoprotein related to cell proliferation is the receptor for transferrin. Proc. Natl. Acad. Sci., 1981, 78 (5), 3039-3043.
7. Faulk, W. P.; Hsi, B. L.; Stevens, P. J. Transferrin and transferrin receptors in carcinoma of the breast. Lancet (London, England) 1980, 2 (8191), 390-392.
8. Schulman, H. M.; Wilczynska, A.; Ponka, P. Transferrin and iron uptake by human lymphoblastoid and K-562 cells. Biochemical and biophysical research communications 1981, 100 (4), 1523-1530.
9. Panaccio, M.; Zalcberg, J. R.; Thompson, C. H.; Leyden, M. J.; Sullivan, J. R.; Lichtenstein, M.; McKenzie, I. F. Heterogeneity of the human transferrin receptor and use of anti-transferrin receptor antibodies to detect tumours in vivo. Immunol. Cell Biol., 1987, 65 (6), 461-472.
10. Dufes, C.; Al Robaian, M.; Somani, S. Transferrin and the transferrin receptor for the targeted delivery of therapeutic agents to the brain and cancer cells. Ther. Deliv., 2013, 4 (5), 629-640.
11. Daniels, T.; Delgado, T.; Rodriguez, J.; Helguera, G.; Penichet, M. The transferrin receptor part I: Biology and targeting with cytotoxic antibodies for the treatment of cancer. Clin. Immunol., 2006, 121 (2), 144-158.
12. Taetle, R.; Castagnola, J.; Mendelsohn, J. Mechanisms of growth inhibition by anti-transferrin receptor monoclonal antibodies. Cancer Res., 1986, 46 (4), 1759-1763.
13. Mendelsohn, J.; Trowbridge, I.; Castagnola, J. Inhibition of human lymphocyte proliferation by monoclonal antibody to transferrin receptor. Blood, 1983, 62 (4), 821-826.
14. Taetle, R.; Honeysett, J. M.; Trowbridge, I. Effects of antitransferrin receptor antibodies on growth of normal and malignant myeloid cells. Int. J. Cancer, 1983, 32 (3), 343-349.
15. Trowbridge, I. S.; Lopez, F. Monoclonal antibody to transferrin receptor blocks transferrin binding and inhibits human tumor cell growth in vitro. Proc. Natl. Acad. Sci. U. S. A., 1982, 79 (4), 1175-1179.
16. Dautry Varsat, A.; Ciechanover, A.; Lodish, H. F. pH and the recycling of transferrin during receptor-mediated endocytosis. Proc. Natl. Acad. Sci. U. S. A., 1983, 80 (8), 2258-2262.
17. Klausner, R. D.; Ashwell, G.; van Renswoude, J.; Harford, J. B.; Bridges, K. R. Binding of apotransferrin to K562 cells: explanation of the transferrin cycle. Proc. Natl. Acad. Sci. U. S. A., 1983, 80 (8), 2263-2266.
18. Ciechanover, A.; Schwartz, A. L.; Dautry V. A.; Lodish, H. F. Kinetics of internalization and recycling of transferrin and the transferrin receptor in a human hepatoma cell line. Effect of lysosomotropic agents. J. Biol. Chem., 1983, 258 (16), 9681-9689.
19. Faulk, W. P.; Barabas, K.; Sun, I. L.; Crane, F. L. Transferrinadriamycin conjugates which inhibit tumor cell proliferation without interaction with DNA inhibit plasma membrane oxidoreductase and proton release in K562 cells. Biochem. Int., 1991, 25 (5), 815-22.
20. Bejaoui, N.; Page, M.; Noel, C. Cytotoxicity of transferrindaunorubicin conjugates on small cell carcinoma of the lung (SCCL) cell line NCI-H69. Anticancer Res., 1991, 11 (6), 2211-3.
21. Trowbridge, I. S.; Domingo, D. L. Anti-transferrin receptor monoclonal antibody and toxin-antibody conjugates affect growth of human tumour cells. Nature, 1981, 294 (5837), 171-173.
22. Lemieux, P.; Page, M. Sensitivity of multidrug-resistant MCF-7 cells to a transferrin-doxorubicin conjugate. Anticancer Res., 1994, 14 (2A), 397-403.
23. Daniels, T. R.; Ng, P. P.; Delgado, T.; Lynch, M. R.; Schiller, G.; Helguera, G.; Penichet, M. L. Conjugation of an anti transferrin receptor IgG3-avidin fusion protein with biotinylated saporin results in significant enhancement of its cytotoxicity against malignant hematopoietic cells. Mol. Cancer Ther., 2007, 6 (11), 2995-3008.
24. Descamps, L.; Dehouck, M. P.; Torpier, G.; Cecchelli, R. Receptor-mediated transcytosis of transferrin through blood-brain barrier endothelial cells. Am. J. Physiol., 1996, 270 (4), H1149-H1158.
25. Ulbrich, K.; Hekmatara, T.; Herbert, E.; Kreuter, J. Transferrinand transferrin-receptor-antibody-modified nanoparticles enable drug delivery across the blood-brain barrier (BBB). Eur. J. Pharm. Biopharm., 2009, 71 (2), 251-256.
26. Friden, P. M.; Walus, L. R.; Musso, G. F.; Taylor, M. A.; Malfroy, B.; Starzyk, R. M. Anti-transferrin receptor antibody and antibodydrug conjugates cross the blood-brain barrier. Proceedings of the Natl. Acad. Sci. U. S. A. 1991, 88 (11), 4771-4775.
27. Martell, L. A.; Agrawal, A.; Ross, D. A.; Muraszko, K. M. Efficacy of Transferrin Receptor-targeted Immunotoxins in Brain Tumor Cell Lines and Pediatric Brain Tumors. Cancer Res., 1993, 53 (6), 1348-1353.
28. Berczi, A.; Barabas, K.; Sizensky, J. A.; Faulk, W. P. Adriamycin conjugates of human transferrin bind transferrin receptors and kill K562 and HL60 cells. Arch. Biochem. Biophys., 1993, 300 (1), 356-63.
29. Singh, M.; Atwal, H.; Micetich, R. Transferrin directed delivery of adriamycin to human cells. Anticancer Res., 1998, 18 (3A), 1423-7.
30. Wang, F.; Jiang, X.; Yang, D. C.; Elliott, R. L.; Head, J. F. Doxorubicin-gallium-transferrin conjugate overcomes multidrug resistance: evidence for drug accumulation in the nucleus of drug resistant MCF-7/ADR cells. Anticancer Res., 2000, 20 (2A), 799-808.
31. Lubgan, D.; Jozwiak, Z.; Grabenbauer, G. G.; Distel, L. V. Doxorubicin-transferrin conjugate selectively overcomes multidrug resistance in leukaemia cells. Cell Mol. Biol. Lett., 2009, 14 (1), 113-27.
32. Szwed, M.; Matusiak, A.; Laroche-Clary, A.; Robert, J.; Marszalek, I.; Jozwiak, Z. Transferrin as a drug carrier: Cytotoxicity, cellular uptake and transport kinetics of doxorubicin transferrin conjugate in the human leukemia cells. Toxicol. in Vitro 2014, 28, 187-97.
33. Karagiannis, T. C.; Lobachevsky, P. N.; Leung, B. K.; White, J. M.; Martin, R. F. Receptor-mediated DNA-targeted photoimmunotherapy. Cancer Res., 2006, 66 (21), 10548-52.
34. Peer, D.; Margalit, R. Fluoxetine and reversal of multidrug resistance. Cancer Lett., 2006, 237 (2), 180-187.
35. Suri, S.; Fenniri, H.; Singh, B. Nanotechnology-based drug delivery systems. J. Occup. Med. Toxicol., 2007, 2 (1), 16.
36. Jabir, N. R.; Tabrez, S.; Ashraf, G. M.; Shakil, S.; Damanhouri, G. A.; Kamal, M. A., Nanotechnology-based approaches in anticancer research. Intl. J. Nanomed., 2012, 7, 4391-4408.
37. Ali, I.; Rahis, U.; Salim, K.; A. Rather, M.; A. Wani, W.; Haque, A. Advances in Nano Drugs for Cancer Chemotherapy. Curr. Cancer Drug Targets, 2011, 11 (2), 135-146.
38. Iinuma, H.; Maruyama, K.; Okinaga, K.; Sasaki, K.; Sekine, T.; Ishida, O.; Ogiwara, N.; Johkura, K.; Yonemura, Y. Intracellular targeting therapy of cisplatin-encapsulated transferrin-polyethylene glycol liposome on peritoneal dissemination of gastric cancer. Int. J. Cancer, 2002, 99 (1), 130-7.
39. Sahoo, S. K.; Ma, W.; Labhasetwar, V. Efficacy of transferrinconjugated paclitaxel-loaded nanoparticles in a murine model of prostate cancer. Int. J. Cancer 2004, 112 (2), 335-340.
40. Li, X.; Ding, L.; Xu, Y.; Wang, Y.; Ping, Q. Targeted delivery of doxorubicin using stealth liposomes modified with transferrin. Int. J. Pharm., 2009, 373 (1-2), 116-23.
41. Huang, Y.; He, L.; Liu, W.; Fan, C.; Zheng, W.; Wong, Y.-S.; Chen, T. Selective cellular uptake and induction of apoptosis of cancer-targeted selenium nanoparticles. Biomaterials, 2013, 34 (29), 7106-7116.
42. Gottesman, M. M.; Fojo, T.; Bates, S. E. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat. Rev. Cancer, 2002, 2 (1), 48-58.
43. Jain, R. K. Delivery of molecular and cellular medicine to solid tumors. Adv. Drug Deliv. Rev., 2001, 46 (1-3), 149-168.
44. Sahoo, S. K.; Labhasetwar, V. Enhanced Antiproliferative Activity of Transferrin-Conjugated Paclitaxel-Loaded Nanoparticles Is Mediated via Sustained Intracellular Drug Retention. Mol. Pharm., 2005, 2 (5), 373-383.
45. Wu, J.; Lu, Y.; Lee, A.; Pan, X.; Yang, X.; Zhao, X.; Lee, R. Reversal of multidrug resistance by transferrin-conjugated liposomes co-encapsulating doxorubicin and verapamil. J. Pharmacy Pharm. Sci., 2007, 10 (3), 350-357.
46. Bae, S.; Ma, K.; Kim, T. H.; Lee, E. S.; Oh, K. T.; Park, E.-S.; Lee, K. C.; Youn, Y. S. Doxorubicin-loaded human serum albumin nanoparticles surface-modified with TNF-related apoptosisinducing ligand and transferrin for targeting multiple tumor types. Biomaterials, 2012, 33 (5), 1536-1546.
47. Derycke, A. S.; Kamuhabwa, A.; Gijsens, A.; Roskams, T.; De Vos, D.; Kasran, A.; Huwyler, J.; Missiaen, L.; de Witte, P. A. Transferrin-conjugated liposome targeting of photosensitizer AlPcS4 to rat bladder carcinoma cells. J. Natl. Cancer Inst., 2004, 96 (21), 1620-30.
48. Zheng, Y.; Yu, B.; Weecharangsan, W.; Piao, L.; Darby, M.; Mao, Y.; Koynova, R.; Yang, X.; Li, H.; Xu, S.; Lee, L. J.; Sugimoto, Y.; Brueggemeier, R. W.; Lee, R. Transferrin-conjugated lipid-coated PLGA nanoparticles for targeted delivery of aromatase inhibitor 7alpha-APTADD to breast cancer cells. Int. J. Pharm., 2010, 390 (2), 234-41.
49. Ferris, D. P.; Lu, J.; Gothard, C.; Yanes, R.; Thomas, C. R.; Olsen, J. C.; Stoddart, J. F.; Tamanoi, F.; Zink, J. I. Synthesis of biomolecule-modified mesoporous silica nanoparticles for targeted hydrophobic drug delivery to cancer cells. Small, 2011, 7 (13), 1816-26.
50. Pack, D. W.; Hoffman, A. S.; Pun, S.; Stayton, P. S. Design and development of polymers for gene delivery. Nat. Rev. Drug Discov., 2005, 4 (7), 581-593.
51. Li, Y.; Ogris, M.; Wagner, E.; Pelisek, J.; Ruffer, M. Nanoparticles bearing polyethyleneglycol-coupled transferrin as gene carriers: preparation and in vitro evaluation. Int. J. Pharm., 2003, 259 (1-2), 93-101.
52. Xu, L.; Pirollo, K. F.; Chang, E. H. Transferrin-liposome-mediated p53 sensitization of squamous cell carcinoma of the head and neck to radiation in vitro. Hum. Gene Ther., 1997, 8 (4), 467-75.
53. Xu, L.; Pirollo, K. F.; Tang, W. H.; Rait, A.; Chang, E. H. Transferrin-liposome-mediated systemic p53 gene therapy in combination with radiation results in regression of human head and neck cancer xenografts. Hum. Gene Ther., 1999, 10 (18), 2941-52.
54. Xu, L.; Frederik, P.; Pirollo, K. F.; Tang, W. H.; Rait, A.; Xiang, L. M.; Huang, W.; Cruz, I.; Yin, Y.; Chang, E. H. Self-assembly of a virus-mimicking nanostructure system for efficient tumor-targeted gene delivery. Hum. Gene Ther., 2002, 13 (3), 469-81.
55. Qian, C.; Liu, X. Y.; Prieto, J. Therapy of cancer by cytokines mediated by gene therapy approach. Cell Res., 2006, 16 (2), 182-188.
56. Qian, C.; Sangro, B.; Prieto, J. New strategies to enhance gene therapy efficiency. Gastroenterology, 2002, 123(2), 639-42.
57. Koppu, S.; Oh, Y. J.; Edrada-Ebel, R.; Blatchford, D. R.; Tetley, L.; Tate, R. J.; Dufès, C. Tumor regression after systemic administration of a novel tumor-targeted gene delivery system carrying a therapeutic plasmid DNA. J. Control. Release, 2010, 143 (2), 215-221.
58. Zhuo, H.; Peng, Y.; Yao, Q.; Zhou, N.; Zhou, S.; He, J.; Fang, Y.; Li, X.; Jin, H.; Lu, X.; Zhao, Y. Tumor imaging and interferongamma-inducible protein-10 gene transfer using a highly efficient transferrin-conjugated liposome system in mice. Clin. Cancer Res., 2013, 19 (15), 4206-17.
59. Juliano, R. L.; Ming, X.; Nakagawa, O. Cellular uptake and intracellular trafficking of antisense and siRNA oligonucleotides. Bioconjug. Chem., 2012, 23 (2), 147-57.
60. Liu, T. G.; Yin, J. Q.; Shang, B. Y.; Min, Z.; He, H. W.; Jiang, J. M.; Chen, F.; Zhen, Y. S.; Shao, R. G. Silencing of hdm2 oncogene by siRNA inhibits p53-dependent human breast cancer. Cancer Gene Ther., 2004, 11 (11), 748-56.
61. Zhao, G. T.; Yang, L. J.; Li, X. X.; Cui, H. L.; Guo, R. Expression of the Proto-oncogene Pokemon in Colorectal Cancer-Inhibitory Effects of an siRNA. Asian Pac. J. Cancer Prev., 2013, 14 (9), 4999-5005.
62. Lee, J. H.; Cho, E. S.; Kim, M. Y.; Seo, Y. W.; Kho, D. H.; Chung, I. J.; Kook, H.; Kim, N. S.; Ahn, K. Y.; Kim, K. K. Suppression of progression and metastasis of established colon tumors in mice by intravenous delivery of short interfering RNA targeting KITENIN, a metastasis-enhancing protein. Cancer Res., 2005, 65 (19), 8993-9003.
63. Liu, C.; Qureshi, I. A.; Ding, X.; Shan, Y.; Huang, Y.; Xie, Y.; Ji, M. Modulation of multidrug resistance gene (mdr-1) with antisense oligodeoxynucleotides. Clin. Sci., 1996, 91 (1), 93-8.
64. Logashenko, E. B.; Vladimirova, A. V.; Repkova, M. N.; Venyaminova, A. G.; Chernolovskaya, E. L.; Vlassov, V. V. Silencing of MDR 1 gene in cancer cells by siRNA. Nucleosides Nucleotides Nucleic Acids, 2004, 23 (6-7), 861-6.
65. Juliano, R.; Bauman, J.; Kang, H.; Ming, X. Biological barriers to therapy with antisense and siRNA oligonucleotides. Mol. Pharm., 2009, 6 (3), 686-95.
66. Whitehead, K. A.; Langer, R.; Anderson, D. G. Knocking down barriers: advances in siRNA delivery. Nat. Rev. Drug Discov., 2009, 8 (2), 129-38.
67. Akhtar, S.; Benter, I. F. Nonviral delivery of synthetic siRNAs in vivo. J. Clin. Invest., 2007, 117 (12), 3623-32.
68. Tamura, A.; Nagasaki, Y. Smart siRNA delivery systems based on polymeric nanoassemblies and nanoparticles. Nanomedicine, 2010, 5 (7), 1089-102.
69. Vaux, D. L.; Cory, S.; Adams, J. M. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature, 1988, 335 (6189), 440-2.
70. Adams, J. M.; Cory, S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene, 2007, 26 (9), 1324-37.
71. Jiang, H.; Xia, D.; Wu, L. J.; Chen, Z. D. Inhibition of Bcl-2 enhances the efficacy of epirubicin chemotherapy in PC-3 prostate cancer cells. Chin. Med. J., 2011, 124 (23), 4018-21.
72. Loriot, Y.; Mordant, P.; Brown, B. D.; Bourhis, J.; Soria, J. C.; Deutsch, E. Inhibition of BCL-2 in small cell lung cancer cell lines with oblimersen, an antisense BCL-2 oligodeoxynucleotide (ODN): in vitro and in vivo enhancement of radiation response. Anticancer Res., 2010, 30 (10), 3869-78.
73. Pellecchia, M.; Reed, J. C. Inhibition of anti-apoptotic Bcl-2 family proteins by natural polyphenols: new avenues for cancer chemoprevention and chemotherapy. Curr. Pharm. Des., 2004, 10 (12), 1387-98.
74. Richardson, A.; Kaye, S. B. Pharmacological inhibition of the Bcl-2 family of apoptosis regulators as cancer therapy. Curr. Mol. Pharmacol., 2008, 1 (3), 244-54.
75. Chiu, S.-J.; Liu, S.; Perrotti, D.; Marcucci, G.; Lee, R. Efficient delivery of a Bcl-2-specific antisense oligodeoxyribonucleotide (G3139) via transferrin receptor-targeted liposomes. J. Control. Release, 2006, 112 (2), 199-207.
76. Mendonca, L. S.; Firmino, F.; Moreira, J. N.; Pedroso de Lima, M. C.; Simoes, S. Transferrin receptor-targeted liposomes encapsulating anti-BCR-ABL siRNA or asODN for chronic myeloid leukemia treatment. Bioconjug. Chem., 2010, 21 (1), 157-68.
77. Vinogradov, S.; Batrakova, E.; Li, S.; Kabanov, A. Polyion complex micelles with protein-modified corona for receptormediated delivery of oligonucleotides into cells. Bioconjug. Chem., 1999, 10 (5), 851-60.
78. Smith, Q. R. A review of blood-brain barrier transport techniques. Methods Mol. Med., 2003, 89, 193-208.
79. Bodor, N.; Brewster, M. E. Problems of delivery of drugs to the brain. Pharmacol. Ther., 1982, 19 (3), 337-86.
80. Ren, W. H.; Chang, J.; Yan, C. H.; Qian, X. M.; Long, L. X.; He, B.; Yuan, X. B.; Kang, C. S.; Betbeder, D.; Sheng, J.; Pu, P. Y. Development of transferrin functionalized poly(ethylene glycol)/poly(lactic acid) amphiphilic block copolymeric micelles as a potential delivery system targeting brain glioma. J. Mater. Sci. Mater. Med., 2010, 21 (9), 2673-81.
81. Chang, J.; Paillard, A.; Passirani, C.; Morille, M.; Benoit, J. P.; Betbeder, D.; Garcion, E. Transferrin adsorption onto PLGA nanoparticles governs their interaction with biological systems from blood circulation to brain cancer cells. Pharm. Res., 2012, 29 (6), 1495-505.
82. Hau, P.; Fabel, K.; Baumgart, U.; Rümmele, P.; Grauer, O.; Bock, A.; Dietmaier, C.; Dietmaier, W.; Dietrich, J.; Dudel, C.; Hübner, F.; Jauch, T.; Drechsel, E.; Kleiter, I.; Wismeth, C.; Zellner, A.; Brawanski, A.; Steinbrecher, A.; Marienhagen, J.; Bogdahn, U. Pegylated liposomal doxorubicin-efficacy in patients with recurrent high-grade glioma. Cancer, 2004, 100 (6), 1199-1207.
83. Merker, P. C.; Lewis, M. R.; Walker, M. D.; Richardson Jr, E. P. Neurotoxicity of adriamycin (Doxorubicin) perfused through the cerebrospinal fluid spaces of the rhesus monkey. Toxicol. Applied Pharmacol., 1978, 44 (1), 191-205.
84. Neuwelt, E. A.; Pagel, M.; Barnett, P.; Glassberg, M.; Frenkel, E. P. Pharmacology and Toxicity of Intracarotid Adriamycin Administration Following Osmotic Blood-Brain Barrier Modification. Cancer Res., 1981, 41 (11 Part 1), 4466-4470.
85. Ohnishi, T.; Tamai, I.; Sakanaka, K.; Sakata, A.; Yamashima, T.; Yamashita, J.; Tsuji, A. In vivo and in vitro evidence for ATPdependency of P-glycoprotein-mediated efflux of doxorubicin at the blood-brain barrier. Biochem. Pharmacol., 1995, 49 (10), 1541-1544.
86. Lesniak, M. S.; Upadhyay, U.; Goodwin, R.; Tyler, B.; Brem, H. Local delivery of doxorubicin for the treatment of malignant brain tumors in rats. Anticancer Res., 2005, 25 (6B), 3825-31.
87. Stan, A. C.; Casares, S.; Radu, D.; Walter, G. F.; Brumeanu, T. D. Doxorubicin-induced cell death in highly invasive human gliomas. Anticancer Res., 1999, 19 (2A), 941-50.
88. Cimini, A.; Mei, S.; Benedetti, E.; Laurenti, G.; Koutris, I.; Cinque, B.; Cifone, M. G.; Galzio, R.; Pitari, G.; Di Leandro, L.; Giansanti, F.; Lombardi, A.; Fabbrini, M. S.; Ippoliti, R. Distinct cellular responses induced by saporin and a transferrin-saporin conjugate in two different human glioblastoma cell lines. J. Cell Physiol., 2012, 227 (3), 939-51.
89. Weaver, M.; Laske, D. W. Transferrin receptor ligand-targeted toxin conjugate (Tf-CRM107) for therapy of malignant gliomas. J. Neurooncol., 2003, 65 (1), 3-13.
90. Liu, G.; Mao, J.; Jiang, Z.; Sun, T.; Hu, Y.; Zhang, C.; Dong, J.; Huang, Q.; Lan, Q. Transferrin-modified Doxorubicin-loaded biodegradable nanoparticles exhibit enhanced efficacy in treating brain glioma-bearing rats. Cancer Biother. Radiopharm., 2013, 28 (9), 691-696.
91. Li, Y.; He, H.; Jia, X.; Lu, W.-L.; Lou, J.; Wei, Y. A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas. Biomaterials, 2012, 33 (15), 3899-3908.
92. Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P. Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors. Life Sci., 1988, 42 (24), 2457-2465.
93. Kayyali, R.; Marriott, C.; Wiseman, H. Tamoxifen decreases drug efflux from liposomes: relevance to its ty to reverse multidrug resistance in cancer cells? FEBS Lett., 1994, 344 (2-3), 221-224.
94. Pulkkinen, M.; Pikkarainen, J.; Wirth, T.; Tarvainen, T.; Haapaaho, V.; Korhonen, H.; Seppala, J.; Jarvinen, K. Three-step tumor targeting of paclitaxel using biotinylated PLA-PEG nanoparticles and avidin-biotin technology: Formulation development and in vitro anticancer activity. Eur. J. Pharm. Biopharm., 2008, 70 (1), 66-74.
95. Shah, N.; Chaudhari, K.; Dantuluri, P.; Murthy, R. S.; Das, S. Paclitaxel-loaded PLGA nanoparticles surface modified with transferrin and Pluronic(R)P85, an in vitro cell line and in vivo biodistribution studies on rat model. J. Drug Target, 2009, 17 (7), 533-42.
96. Gan, C. W.; Feng, S. S. Transferrin-conjugated nanoparticles of poly(lactide)-D-alpha-tocopheryl polyethylene glycol succinate diblock copolymer for targeted drug delivery across the blood-brain barrier. Biomaterials, 2010, 31 (30), 7748-57.
97. Jiang, L.-Y.; He, S.; Jiang, K.-Z.; Sun, C.-R.; Pan, Y.-J. Resveratrol and its oligomers from wine grapes are selective (1)O2 quenchers: mechanistic implication by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry and theoretical calculation. J. Agricul. Food Chem., 2010, 58 (16), 9020-9027.
98. Castino, R.; Pucer, A.; Veneroni, R.; Morani, F.; Peracchio, C.; Lah, T.; Isidoro, C. Resveratrol reduces the invasive growth and promotes the acquisition of a long-lasting differentiated phenotype in human glioblastoma cells. J. Agricul Food Chem., 2011, 59 (8), 4264-4272.
99. Sanna, V.; Roggio, A.; Siliani, S.; Piccinini, M.; Marceddu, S.; Mariani, A.; Sechi, M. Development of novel cationic chitosan-and anionic alginate-coated poly(D, L-lactide-co-glycolide) nanoparticles for controlled release and light protection of resveratrol. Intl. J. Nanomed., 2012, 7, 5501-5516.
100. Guo, W.; Li, A.; Jia, Z.; Yuan, Y.; Dai, H.; Li, H. Transferrin modified PEG-PLA-resveratrol conjugates: In vitro and in vivo studies for glioma. Eur. J. Pharmacol., 2013, 718, 41-7.
101. Caravan, P.; Ellison, J. J.; McMurry, T. J.; Lauffer, R. B., Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications. Chem. Rev., 1999, 99 (9), 2293-352.
102. McAteer, M. A.; Choudhury, R. P. Chapter 4-Applications of nanotechnology in molecular imaging of the brain. Prog. Brain Res., 2009, 180, 72-96.
103. Minchin, R.; Martin, D., Nanoparticles for molecular imaging--an overview. Endocrinology, 2009, 151 (2), 474-481.
104. Korotcov, A.; Shan, L.; Meng, H.; Wang, T.; Sridhar, R.; Zhao, Y.; Liang, X. J.; Wang, P. C. A nanocomplex system as targeted contrast agent delivery vehicle for magnetic resonance imaging dynamic contrast enhancement study. J. Nanosci. Nanotechnol., 2010, 10 (11), 7545-9.
105. Jiang, W.; Xie, H.; Ghoorah, D.; Shang, Y.; Shi, H.; Liu, F.; Yang, X.; Xu, H. Conjugation of functionalized SPIONs with transferrin for targeting and imaging brain glial tumors in rat model. PLoS One, 2012, 7 (5), e37376.
106. Korkusuz, H.; Ulbrich, K.; Welzel, K.; Koeberle, V.; Watcharin, W.; Bahr, U.; Chernikov, V.; Knobloch, T.; Petersen, S.; Huebner, F.; Ackermann, H.; Gelperina, S.; Kromen, W.; Hammerstingl, R.; Haupenthal, J.; Gruenwald, F.; Fiehler, J.; Zeuzem, S.; Kreuter, J.; Vogl, T. J.; Piiper, A. Transferrin-coated gadolinium nanoparticles as MRI contrast agent. Mol. Imaging Biol., 2013, 15 (2), 148-54.
107. Anthony, D. C.; Sibson, N. R.; McAteer, M. A.; Davis, B.; Choudhury, R. P. Detection of brain pathology by magnetic resonance imaging of iron oxide micro-particles. Methods Mol. Biol., 2011, 686, 213-27.
108. Chen, M. L.; He, Y. J.; Chen, X. W.; Wang, J. H. Quantum dots conjugated with Fe3O4-filled carbon nanotubes for cancer-targeted imaging and magnetically guided drug delivery. Langmuir, 2012, 28 (47), 16469-76.
109. Suzuki, R.; Takizawa, T.; Kuwata, Y.; Mutoh, M.; Ishiguro, N.; Utoguchi, N.; Shinohara, A.; Eriguchi, M.; Yanagie, H.; Maruyama, K. Effective anti-tumor activity of oxaliplatin encapsulated in transferrin-PEG-liposome. Intl. J. Pharm., 2008, 346 (1-2), 143-150.
110. Izbicka, E.; Diaz, A.; Campos, D.; Wick, M.; Takimoto, C.; Nagasawa, M.; Hashimoto, C. In Evaluation of antitumor activity and biomarkers for MBP-426 in human pancreatic cancer xenograft models in vivo American Association for Cancer Research (AACR), Mebiopharm Co. Ltd. 2007.
111. Senzer, N.; Nemunaitis, J.; Nemunaitis, D.; Bedell, C.; Edelman, G.; Barve, M.; Nunan, R.; Pirollo, K. F.; Rait, A.; Chang, E. H. Phase I study of a systemically delivered p53 nanoparticle in advanced solid tumors. Mol. Ther., 2013, 21 (5), 1096-103.
112. Camp, E. R.; Wang, C.; Little, E. C.; Watson, P. M.; Pirollo, K. F.; Rait, A.; Cole, D. J.; Chang, E. H.; Watson, D. K. Transferrin receptor targeting nanomedicine delivering wild-type p53 gene sensitizes pancreatic cancer to gemcitabine therapy. Cancer Gene Ther., 2013, 20 (4), 222-8.
113. Pirollo, K. F.; Rait, A.; Zhou, Q.; Zhang, X. Q.; Zhou, J.; Kim, C. S.; Benedict, W. F.; Chang, E. H. Tumor-targeting nanocomplex delivery of novel tumor suppressor RB94 chemosensitizes bladder carcinoma cells in vitro and in vivo. Clin. Cancer Res., 2008, 14 (7), 2190-8.
114. Davis, M. E. The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: from concept to clinic. Mol. Pharm., 2009, 6 (3), 659-68.
115. Rahman, M.; Amin, A. R. M. R.; Wang, X.; Zuckerman, J.; Choi, C. H. J.; Zhou, B.; Wang, D.; Nannapaneni, S.; Koenig, L.; Chen, Z.; Yen, Y.; Davis, M.; Shin, D. Systemic delivery of siRNA nanoparticles targeting RRM2 suppresses head and neck tumor growth. J. Control. Release, 2012, 159 (3), 384-392.
116. Heidel, J. D.; Yu, Z.; Liu, J. Y. C.; Rele, S. M.; Liang, Y.; Zeidan, R. K.; Kornbrust, D. J.; Davis, M. E. Inaugural Article: Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNA. Proc. Natl. Acad. Sci. U. S. A., 2007, 104 (14), 5715-5721.
117. Jain, A.; Jain, S. PEGylation: an approach for drug delivery. A review. Crit. Rev. Ther. Drug Carrier Systems, 2008, 25 (5), 403-447.
118. Gabizon, A. A. Pegylated liposomal doxorubicin: metamorphosis of an old drug into a new form of chemotherapy. Cancer Investig., 2001, 19 (4), 424-436.
119. Otsuka, H.; Nagasaki, Y.; Kataoka, K. PEGylated nanoparticles for biological and pharmaceutical applications. Adv. Drug Deliv. Rev., 2003, 55 (3), 403-419.
120. Gref, R.; Lück, M.; Quellec, P.; Marchand, M.; Dellacherie, E.; Harnisch, S.; Blunk, T.; Müller, R. H. 'Stealth' corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. Colloids Surfaces B: Biointerfaces, 2000, 18 (3-4), 301-313.
121. Cheng, J.; Teply, B. A.; Sherifi, I.; Sung, J.; Luther, G.; Gu, F. X.; Levy-Nissenbaum, E.; Radovic-Moreno, A. F.; Langer, R.; Farokhzad, O. C. Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery. Biomaterials, 2007, 28 (5), 869-876.
122. Veronese, F. M.; Pasut, G. PEGylation, successful approach to drug delivery. Drug Discov. Today, 2005, 10 (21), 1451-1458.
123. Bartlett, D. W.; Su, H.; Hildebrandt, I. J.; Weber, W. A.; Davis, M. E. Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging. Proc. Natl. Acad. Sci. U. S. A., 2007, 104 (39), 15549-54.
124. Bae, S.; Ma, K.; Kim, T. H.; Lee, E. S.; Oh, K. T.; Park, E. S.; Lee, K. C.; Youn, Y. S. Doxorubicin-loaded human serum albumin nanoparticles surface-modified with TNF-related apoptosisinducing ligand and transferrin for targeting multiple tumor types. Biomaterials, 2012, 33 (5), 1536-46.
125. Xu, Q.; Liu, Y.; Su, S.; Li, W.; Chen, C.; Wu, Y. Anti-tumor activity of paclitaxel through dual-targeting carrier of cyclic RGD and transferrin conjugated hyperbranched copolymer nanoparticles. Biomaterials, 2012, 33 (5), 1627-39.
126. Salvati, A.; Pitek, A. S.; Monopoli, M. P.; Prapainop, K.; Bombelli, F. B.; Hristov, D. R.; Kelly, P. M.; Aberg, C.; Mahon, E.; Dawson, K. A. Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface. Nat. Nanotechnol., 2013, 8 (2), 137-43.
127. Chang, J.; Paillard, A.; Passirani, C.; Morille, M.; Benoit, J.-P.; Betbeder, D.; Garcion, E. Transferrin adsorption onto PLGA nanoparticles governs their interaction with biological systems from blood circulation to brain cancer cells. Pharm. Res., 2012, 29 (6), 1495-1505.
128. Cui, Y.; Xu, Q.; Chow, P. K.; Wang, D.; Wang, C. H. Transferrinconjugated magnetic silica PLGA nanoparticles loaded with doxorubicin and paclitaxel for brain glioma treatment. Biomaterials, 2013, 34 (33), 8511-20.
129. Xu, Q.; Liu, Y.; Su, S.; Li, W.; Chen, C.; Wu, Y., Anti-tumor activity of paclitaxel through dual-targeting carrier of cyclic RGD and transferrin conjugated hyperbranched copolymer nanoparticles. Biomaterials, 2012, 33 (5), 1627-1639.
130. Gaspar, M. M.; Radomska, A.; Gobbo, O. L.; Bakowsky, U.; Radomski, M. W.; Ehrhardt, C., Targeted delivery of transferrinconjugated liposomes to an orthotopic model of lung cancer in nude rats. J. Aerosol. Med. Pulm. Drug Deliv., 2012, 25 (6), 310-8.
131. Jing, F.; Li, J.; Liu, D.; Wang, C.; Sui, Z., Dual ligands modified double targeted nano-system for liver targeted gene delivery. Pharm. Biol., 2013, 51 (5), 643-9.
132. Korotcov, A.; Shan, L.; Meng, H.; Wang, T.; Sridhar, R.; Zhao, Y.; Liang, X.-J.; Wang, P. A nanocomplex system as targeted contrast agent delivery vehicle for magnetic resonance imaging dynamic contrast enhancement study. J. Nanosci. Nanotechnol., 2010, 10 (11), 7545-7549.
133. Jiang, W.; Xie, H.; Ghoorah, D.; Shang, Y.; Shi, H.; Liu, F.; Yang, X.; Xu, H. Conjugation of functionalized SPIONs with transferrin for targeting and imaging brain glial tumors in rat model. PLoS ONE, 2012, 7 (5), e37376-e37376.
134. Chen, M.-L.; He, Y.-J.; Chen, X.-W.; Wang, J.-H. Quantum dots conjugated with Fe3O4-filled carbon nanotubes for cancer-targeted imaging and magnetically guided drug delivery. Langmuir, 2012, 28 (47), 16469-16476.
135. Korkusuz, H.; Ulbrich, K.; Bihrer, V.; Welzel, K.; Chernikov, V.; Knobloch, T.; Petersen, S.; Huebner, F.; Ackermann, H.; Gelperina, S.; Korkusuz, Y.; Kromen, W.; Hammerstingl, R.; Haupenthal, J. R.; Fiehler, J.; Zeuzem, S.; Kreuter, J. R.; Vogl, T.; Piiper, A. Contrast enhancement of the brain by folate-conjugated gadolinium-diethylenetriaminepentaacetic acid-human serum albumin nanoparticles by magnetic resonance imaging. Mol. Imaging, 2012, 11 (4), 272-279.