Designing the future of nanomedicine: Current barriers to targeted brain therapeutics

European Journal of Nanomedicine

Volumn 6, Issue 3, 2014, Pages 127-139

  Herda, Luciana M ^a   Polo, Ester ^a   Kelly, Philip M ^a   Rocks, Louise ^a   Hudecz, Diána ^a   Dawson, Kenneth A ^a  

^a UNIVERSITY COLLEGE DUBLIN   (Ireland)

Author keywords

apoE; blood brain barrier; drug targeting; nanoparticles; receptor mediated transcytosis; transferrin

Indexed keywords

BLOOD; MEDICAL NANOTECHNOLOGY; NANOPARTICLES;

APOE; BLOOD-BRAIN BARRIER; DRUG-TARGETING; TRANSCYTOSIS; TRANSFERRIN;

NANOSYSTEMS;

APOLIPOPROTEIN; DIPHTHERIA TOXIN RECEPTOR; LIGAND; RECEPTOR; TRANSFERRIN RECEPTOR; UNCLASSIFIED DRUG;

BLOOD BRAIN BARRIER; BODY FLUID; HUMAN; NANOMEDICINE; NONHUMAN; RECEPTOR MEDIATED TRANSCYTOSIS; REVIEW; SPECIES DIFFERENCE; TRANSCYTOSIS;

EID: 84907508928     PISSN: 16625986     EISSN: 1662596X     Source Type: Journal    
DOI: 10.1515/ejnm-2014-0022     Document Type: Review

References (93)

1. Pardridge WM. Drug transport across the blood-brain barrier. J Cereb Blood Flow Metab 2012;32:1959-72.
2. Johanson C, Stopa E, McMillan P. The Blood-Cerebrospinal Fluid Barrier: Structure and Functional Significance. In: Nag S, editor. The Blood-Brain and Other Neural Barriers. Methods in Molecular Biology. vol. 686. New York: Humana Press; 2011. p. 101-31.
3. Abbott NJ, Patabendige AAK, Dolman DEM, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis 2010;37:13-25.
4. Hawkins BT, Egleton RD. Pathophysiology of the Blood-Brain Barrier: Animal Models and Methods. In: Gerald PS, editor. Current Topics in Developmental Biology. Vol. 80. London: Academic Press; 2007. p. 277-309.
5. Abbott NJ, Ronnback L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 2006;7:41-53.
6. Dohgu S, Takata F, Yamauchi A, Nakagawa S, Egawa T, Naito M, et al. Brain pericytes contribute to the induction and up-regulation of blood-brain barrier functions through transforming growth factor- production. Brain Res 2005;1038:208-15.
7. Begley D, Brightman M. Structural and functional aspects of the blood-brain barrier. In: Prokai L, Prokai-Tatrai K, editors. Peptide Transport and Delivery into the Central Nervous System. Progress in Drug Research. vol. 61. Basel: Birkhäuser Verlag; 2003. p. 39-78.
8. Wolburg H, Lippoldt A. Tight junctions of the blood-brain barrier: development, composition and regulation. Vascul Pharmacol 2002;38:323-37.
9. Chiba H, Osanai M, Murata M, Kojima T, Sawada N. Transmembrane proteins of tight junctions. BBA-Biomembranes 2008;1778:588-600.
10. Matter K, Balda MS. Signalling to and from tight junctions. Nat Rev Mol Cell Biol 2003;4:225-37.
11. Simard M, Arcuino G, Takano T, Liu QS, Nedergaard M. Signaling at the gliovascular interface. J Neurosci 2003;23:9254-62.
12. Bernacki J, Dobrowolska A, Nierwinska K, Malecki A. Physiology and pharmacological role of the blood-brain barrier. Pharmacol rep 2008;60:600-22.
13. Clark DE. In silico prediction of blood-brain barrier permeation. Drug Discov Today 2003;8:927-33.
14. Reiber H. Dynamics of brain-derived proteins in cerebrospinal fluid. Clin Chimica Acta 2001;310:173-86.
15. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001;46:3-26.
16. Deeken JF, Löscher W. The Blood-Brain Barrier and Cancer: Transporters, Treatment, and Trojan Horses. Clin Cancer Res 2007;13:1663-74.
17. Loscher W, Potschka H. Drug resistance in brain diseases and the role of drug efflux transporters. Nat Rev Neurosci 2005;6:591-602.
18. Ohtsuki S, Terasaki T. Contribution of carrier-mediated transport systems to the blood-brain barrier as a supporting and protecting interface for the brain; importance for CNS drug discovery and development. Pharm Res 2007;24:1745-58.
19. Simionescu M, Gafencu A, Antohe F. Transcytosis of plasma macromolecules in endothelial cells: A cell biological survey. Microsc Res Tech 2002;57:269-88.
20. Chen Y, Liu L. Modern methods for delivery of drugs across the blood-brain barrier. Adv Drug Deliv Rev 2012;64:640-65.
21. Pardridge WM. Blood-brain barrier drug targeting: The future of brain drug development. Mol Interventions 2003;3: 90-105, 51.
22. Wong HL, Wu XY, Bendayan R. Nanotechnological advances for the delivery of CNS therapeutics. Adv Drug Deliv Rev 2012;64:686-700.
23. Yang H. Nanoparticle-mediated brain-specific drug delivery, imaging, and diagnosis. Pharm Res 2010;27:1759-71.
24. Wong HL, Bendayan R, Rauth AM, Li Y, Wu XY. Chemotherapy with anticancer drugs encapsulated in solid lipid nanoparticles. Adv Drug Deliv Rev 2007;59:491-504.
25. Bendayan R, Lee G, Bendayan M. Functional expression and localization of P-glycoprotein at the blood brain barrier. Microsc Res Tech 2002;57:365-80.
26. Pardridge WM. Re-Engineering Biopharmaceuticals for delivery to brain with molecular Trojan horses. Bioconjugate Chem 2008;19:1327-38.
27. Hoshi Y, Uchida Y, Tachikawa M, Inoue T, Ohtsuki S, Terasaki T. Quantitative atlas of blood-brain barrier transporters, receptors, and tight junction proteins in rats and common marmoset. J Pharm Sci 2013;102:3343-55.
28. Uchida Y, Ohtsuki S, Katsukura Y, Ikeda C, Suzuki T, Kamiie J, et al. Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors. J Neurochem 2011;117:333-45.
29. William MP. Drug transport across the blood-brain barrier. J Cereb Blood Flow Metab 2012;32:1959-72.
30. Rautio J, Gynther M, Laine K. LAT1-mediated prodrug uptake: A way to breach the blood-brain barrier? Ther Deliv 2013;4:281-4.
31. Li X, Qu B, Jin X, Hai L, Wu Y. Design, synthesis and biological evaluation for docetaxel-loaded brain targeting liposome with "lock-in" function. J Drug Target 2013.
32. Hervé F, Ghinea N, Scherrmann J-M. CNS delivery via adsorptive transcytosis. AAPS J 2008;10:455-72.
33. Lu W, Wan J, She Z, Jiang X. Brain delivery property and accelerated blood clearance of cationic albumin conjugated pegylated nanoparticle. J Control Release 2007;118:38-53.
34. Jones A, Shusta E. Blood-brain barrier transport of therapeutics via receptor-mediation. Pharm Res 2007;24:1759-71.
35. Okamoto CT. Endocytosis and transcytosis. Adv Drug Deliv Rev 1998;29:215-28.
36. Michaelis K, Hoffmann MM, Dreis S, Herbert E, Alyautdin RN, Michaelis M, et al. Covalent linkage of apolipoprotein E to albumin nanoparticles strongly enhances drug transport into the brain. J Pharm Exp Ther 2006;317:1246-53.
37. Ulbrich K, Hekmatara T, Herbert E, Kreuter J. Transferrin-And transferrin-receptor-Antibody-modified nanoparticles enable drug delivery across the blood-brain barrier (BBB). Eur J Pharm Biopharm 2009;71:251-6.
38. Ambruosi A, Khalansky AS, Yamamoto H, Gelperina SE, Begley DJ, Kreuter J. Biodistribution of polysorbate 80-coated doxorubicin-loaded [14C]-poly(butyl cyanoacrylate) nanoparticles after intravenous administration to glioblastomabearing rats. J Drug Target 2006;14:97-105.
39. Kreuter J, Shamenkov D, Petrov V, Ramge P, Cychutek K, Koch-Brandt C, et al. Apolipoprotein-mediated transport of nanoparticle-bound drugs across the blood-brain barrier. J Drug Target 2002;10:317-25.
40. Kreuter J, Hekmatara T, Dreis S, Vogel T, Gelperina S, Langer K. Covalent attachment of apolipoprotein A-I and apolipoprotein B-100 to albumin nanoparticles enables drug transport into the brain. J Control Release 2007;118:54-8.
41. Alyautdin RN, Petrov VE, Langer K, Berthold A, Kharkevich DA, Kreuter J. Delivery of loperamide across the blood-brain barrier with polysorbate 80-coated polybutylcyanoacrylate nanoparticles. Pharm Res 1997;14:325-8.
42. Kreuter J, Ramge P, Petrov V, Hamm S, Gelperina SE, Engelhardt B, et al. Direct evidence that polysorbate-80-coated poly(butylcyanoacrylate) nanoparticles deliver drugs to the CNS via specific mechanisms requiring prior binding of drug to the nanoparticles. Pharm Res 2003;20:409-16.
43. Woodcock DM, Linsenmeyer ME, Chojnowski G, Kriegler AB, Nink V, Webster LK, et al. Reversal of multidrug resistance by surfactants. Br J Cancer 1992;66:62-8.
44. Nerurkar MM, Burton PS, Borchardt RT. The use of surfactants to enhance the permeability of peptides through Caco-2 cells by inhibition of an apically polarized efflux system. Pharm Res 1996;13:528-34.
45. Pinzon-Daza M, Garzon R, Couraud P, Romero I, Weksler B, Ghigo D, et al. The association of statins plus LDL receptortargeted liposome-encapsulated doxorubicin increases in vitro drug delivery across blood-brain barrier cells. Br J Pharmacol 2012;167:1431-47.
46. Ueno M, Nakagawa T, Wu B, Onodera M, Huang CL, Kusaka T, et al. Transporters in the brain endothelial barrier. Curr Med Chem 2010;17:1125-38.
47. Wang D, El-Amouri SS, Dai M, Kuan CY, Hui DY, Brady RO, et al. Engineering a lysosomal enzyme with a derivative of receptorbinding domain of apoE enables delivery across the blood-brain barrier. Proc Natl Acad Sci USA 2013;110:2999-3004.
48. Bu G. Apolipoprotein E and its receptors in Alzheimers disease: pathways, pathogenesis and therapy. Nat Rev Neurosci 2009;10:333-44.
49. Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimers disease and other disorders. Nat Rev Neurosci 2011;12:723-38.
50. Nazer B, Hong S, Selkoe DJ. LRP promotes endocytosis and degradation, but not transcytosis, of the amyloid-beta peptide in a blood-brain barrier in vitro model. Neurobiol Dis 2008;30:94-102.
51. Demeule M, Regina A, Ché C, Poirier J, Nguyen T, Gabathuler R, et al. Identification and design of peptides as a new drug delivery system for the brain. J Pharm Exp Ther 2008;324:1064-72.
52. Ren J, Shen S, Wang D, Xi Z, Guo L, Pang Z, et al. The targeted delivery of anticancer drugs to brain glioma by PEGylated oxidized multi-walled carbon nanotubes modified with angiopep-2. Biomaterials 2012;33:3324-33.
53. Huang S, Li J, Han L, Liu S, Ma H, Huang R, et al. Dual targeting effect of Angiopep-2-modified, DNA-loaded nanoparticles for glioma. Biomaterials 2011;32:6832-8.
54. Xin H, Sha X, Jiang X, Chen L, Law K, Gu J, et al. The brain targeting mechanism of Angiopep-conjugated poly(ethylene glycol)-co-poly(epsilon-caprolactone) nanoparticles. Biomaterials 2012;33:1673-81.
55. Krieger M, Herz J. Structures and functions of multiligand lipoprotein receptors: macrophage scavenger receptors and LDL receptor-related protein (LRP). Annu Rev Biochem 1994;63:601-37.
56. Pflanzner T, Janko MC, Andre-Dohmen B, Reuss S, Weggen S, Roebroek AJ, et al. LRP1 mediates bidirectional transcytosis of amyloid-beta across the blood-brain barrier. Neurobiol Aging 2011;32:2323.e1-11.
57. de Boer AG, van der Sandt IC, Gaillard PJ. The role of drug transporters at the blood-brain barrier. Annu rev pharmacol 2003;43:629-56.
58. Wiley DT, Webster P, Gale A, Davis ME. Transcytosis and brain uptake of transferrin-containing nanoparticles by tuning avidity to transferrin receptor. Proc Natl Acad Sci USA 2013;110:8662-7.
59. Yu YJ, Zhang Y, Kenrick M, Hoyte K, Luk W, Lu Y, et al. Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target. Sci Transl Med 2011;3:84ra44.
60. Niewoehner J, Bohrmann B, Collin L, Urich E, Sade H, Maier P, et al. Increased brain penetration and potency of a therapeutic antibody using a monovalent molecular shuttle. Neuron 2014;81:49-60.
61. Boado RJ, Zhang Y, Zhang Y, Wang Y, Pardridge WM. GDNF fusion protein for targeted-drug delivery across the human blood-brain barrier. Biotechnol Bioeng 2008;100:387-96.
62. Fu A, Zhou QH, Hui EK, Lu JZ, Boado RJ, Pardridge WM. Intravenous treatment of experimental Parkinsons disease in the mouse with an IgG-GDNF fusion protein that penetrates the blood-brain barrier. Brain Res 2010;1352:208-13.
63. Boado RJ, Zhou QH, Lu JZ, Hui EK, Pardridge WM. Pharmacokinetics and brain uptake of a genetically engineered bifunctional fusion antibody targeting the mouse transferrin receptor. Mol Pharm 2010;7:237-44.
64. van der Linden RH, Frenken LG, de Geus B, Harmsen MM, Ruuls RC, Stok W, et al. Comparison of physical chemical properties of llama VHH antibody fragments and mouse monoclonal antibodies. Biochim Biophys Acta 1999;1431:37-46.
65. Simister NE, Mostov KE. An Fc receptor structurally related to MHC class I antigens. Nature 1989;337:184-7.
66. Schlachetzki F, Zhu C, Pardridge WM. Expression of the neonatal Fc receptor (FcRn) at the blood-brain barrier. J Neurochem 2002;81:203-6.
67. Roopenian DC, Akilesh S. FcRn: The neonatal Fc receptor comes of age. Nat Rev Immunol 2007;7:715-25.
68. Bien-Ly N, Yu YJ, Bumbaca D, Elstrott J, Boswell CA, Zhang Y, et al. Transferrin receptor (TfR) trafficking determines brain uptake of TfR antibody affinity variants. J Exp Med 2014;211:233-44.
69. Fujita H, Iwabu Y, Tokunaga K, Tanaka Y. Membrane-Associated RING-CH (MARCH) 8 mediates the ubiquitination and lysosomal degradation of the transferrin receptor. J Cell Sci 2013;126(Pt 13):2798-809.
70. Bell RD, Ehlers MD. Breaching the blood-brain barrier for drug delivery. Neuron 2014;81:1-3.
71. Sade H, Baumgartner C, Hugenmatter A, Moessner E, Freskgard PO, Niewoehner J. A human blood-brain barrier transcytosis assay reveals antibody transcytosis influenced by pH-dependent receptor binding. PLoS One 2014;9:e96340.
72. Gaillard PJ, Brink A, de Boer AG. Diphtheria toxin receptortargeted brain drug delivery. Int Congr Ser 2005;1277:185-98.
73. Kuo Y-C, Liu Y-C. Cardiolipin-incorporated liposomes with surface CRM197 for enhancing neuronal survival against neurotoxicity. Int J Pharm 2014;473:334-44.
74. Kuo Y-C, Chung C-Y. Transcytosis of CRM197-grafted polybutylcyanoacrylate nanoparticles for delivering zidovudine across human brain-microvascular endothelial cells. Colloids Surf, B 2012;91:242-9.
75. van Rooy I, Mastrobattista E, Storm G, Hennink WE, Schiffelers RM. Comparison of five different targeting ligands to enhance accumulation of liposomes into the brain. J Control Release 2011;150:30-6.
76. Lee HJ, Engelhardt B, Lesley J, Bickel U, Pardridge WM. Targeting rat anti-mouse transferrin receptor monoclonal antibodies through blood-brain barrier in mouse. J Pharm Exp Ther 2000;292:1048-52.
77. Boado RJ, Zhang Y, Zhang Y, Pardridge WM. Humanization of anti-human insulin receptor antibody for drug targeting across the human blood-brain barrier. Biotechnol Bioeng 2007;96:381-91.
78. Kreuter J, Petrov VE, Kharkevich DA, Alyautdin RN. Influence of the type of surfactant on the analgesic effects induced by the peptide dalargin after its delivery across the blood-brain barrier using surfactant-coated nanoparticles. J Control Release 1997;49:81-7.
79. Couch JA, Yu YJ, Zhang Y, Tarrant JM, Fuji RN, Meilandt WJ, et al. Addressing safety liabilities of TfR bispecific antibodies that cross the blood-brain barrier. Sci Transl Med 2013;5:183ra57.
80. Ohshima-Hosoyama S, Simmons HA, Goecks N, Joers V, Swanson CR, Bondarenko V, et al. A monoclonal antibody-GDNF fusion protein is not neuroprotective and is associated with proliferative pancreatic lesions in parkinsonian monkeys. PloS one 2012;7:e39036.
81. Nonaka N, Farr SA, Kageyama H, Shioda S, Banks WA. Delivery of galanin-like peptide to the brain: Targeting with intranasal delivery and cyclodextrins. J Pharmacol Exp Ther 2008;325:513-9.
82. Anderson NL, Anderson NG. The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics 2002;1:845-67.
83. Monopoli MP, Aberg C, Salvati A, Dawson KA. Biomolecular coronas provide the biological identity of nanosized materials. Nat Nanotechnol 2012;7:779-86.
84. Treuel L, Brandholt S, Maffre P, Wiegele S, Shang L, Nienhaus GU. Impact of protein modification on the protein corona on nanoparticles and nanoparticle-cell interactions. ACS nano 2014;8:503-13.
85. Casals E, Pfaller T, Duschl A, Oostingh GJ, Puntes V. Time evolution of the nanoparticle protein corona. ACS nano 2010;4:3623-32.
86. Tenzer S, Docter D, Kuharev J, Musyanovych A, Fetz V, Hecht R, et al. Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology. Nat Nanotechnol 2013;8:772-81.
87. Deng ZJ, Liang M, Monteiro M, Toth I, Minchin RF. Nanoparticleinduced unfolding of fibrinogen promotes Mac-1 receptor activation and inflammation. Nat Nanotechnol 2011;6:39-44.
88. Maiorano G, Sabella S, Sorce B, Brunetti V, Malvindi MA, Cingolani R, et al. Effects of cell culture media on the dynamic formation of protein-nanoparticle complexes and influence on the cellular response. ACS nano 2010;4:7481-91.
89. Hamad I, Al-Hanbali O, Hunter AC, Rutt KJ, Andresen TL, Moghimi SM. Distinct polymer architecture mediates switching of complement activation pathways at the nanosphere-serum interface: implications for stealth nanoparticle engineering. ACS nano 2010;4:6629-38.
90. Zensi A, Begley D, Pontikis C, Legros C, Mihoreanu L, Wagner S, et al. Albumin nanoparticles targeted with Apo E enter the CNS by transcytosis and are delivered to neurones. J Control Release 2009;137:78-86.
91. Hoshino Y, Koide H, Urakami T, Kanazawa H, Kodama T, Oku N, et al. Recognition, neutralization, and clearance of target peptides in the bloodstream of living mice by molecularly imprinted polymer nanoparticles: A plastic antibody. J Am Chem Soc 2010;132:6644-5.
92. Salvati A, Pitek AS, Monopoli MP, Prapainop K, Bombelli FB, Hristov DR, et al. Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface. Nat Nanotechnol 2013;8:137-43.
93. Zarschler K, Prapainop K, Mahon E, Rocks L, Bramini M, Kelly PM, et al. Diagnostic nanoparticle targeting of the EGFreceptor in complex biological conditions using single-domain antibodies. Nanoscale 2014.