Cell-penetrating peptide-mediated therapeutic molecule delivery into the central nervous system

Current Neuropharmacology

Volumn 11, Issue 2, 2013, Pages 197-208

  Zou, Li Li ^a   Ma, Jie Lan ^a   Wang, Tao ^a   Yang, Tang Bin ^a   Liu, Chang Bai ^a  

^a CHINA THREE GORGES UNIVERSITY   (China)

Author keywords

Blood brain barrier; Cell penetrating peptides; Central nervous system; Drug delivery

Indexed keywords

ABC TRANSPORTER; BETA GALACTOSIDASE; BETA SECRETASE 1; BRAIN DERIVED NEUROTROPHIC FACTOR; BREAST CANCER RESISTANCE PROTEIN; CELL PENETRATING PEPTIDE; CIMETIDINE; CIPROFLOXACIN; DOXORUBICIN; FIBROBLAST GROWTH FACTOR 4; INSULIN RECEPTOR; LEUCINE ENKEPHALIN [2 DEXTRO ALANINE 6 ARGININE]; MORPHINE GLUCURONIDE; MORPHOLINO OLIGONUCLEOTIDE; MULTIDRUG RESISTANCE PROTEIN 1; MULTIDRUG RESISTANCE PROTEIN 4; MULTIDRUG RESISTANCE PROTEIN 5; PACLITAXEL; PENETRATIN; PLASMID DNA; PRAZOSIN; QUANTUM DOT; RNA; SMALL INTERFERING RNA; SOMATOMEDIN B RECEPTOR; SOMATOMEDIN C RECEPTOR; SUPPRESSOR OF CYTOKINE SIGNALING 3; TRANSACTIVATOR PROTEIN; TRANSFERRIN RECEPTOR; UNCLASSIFIED DRUG; UNINDEXED DRUG;

BLOOD BRAIN BARRIER; BRAIN TUMOR; CELL INTERACTION; CENTRAL NERVOUS SYSTEM; DIFFUSION; DRUG DELIVERY SYSTEM; HUMAN; MAJOR HISTOCOMPATIBILITY COMPLEX; NONHUMAN; PINOCYTOSIS; REVIEW;

EID: 84876728629     PISSN: 1570159X     EISSN: 18756190     Source Type: Journal    
DOI: 10.2174/1570159X11311020006     Document Type: Review

References (124)

1. Chen, Y., Liu, L. Modern methods for delivery of drugs across the blood-brain barrier. Adv. Drug. Deliv. Rev., 2011, doi: 10.1016/j. addr. 2011. 11. 010.
2. Abbott, N.J. Dynamics of CNS barriers: evolution, differentiation, and modulation. Cell. Mol. Neurobiol., 2005, 25, 5-23.
3. Cecchell, R., Berezowski, V., Lundquis, S., Culot, M., Renfte, M., Dehouck, M.P., Fenart, L. Modelling of the blood-brain barrier in drug discovery and development. Nat. Rev. Drug Discov., 2007, 6, 650-661.
4. Newton, H.B. Advances in strategies to improve drug delivery to brain tumors. Exp. Rev. Ther., 2006, 6, 1495-1509.
5. Brownlees, J., Williams, C.H. Peptidases, peptides and the mammalian blood-brain barrier. J. Neurochem., 1993, 60, 1089-1096.
6. Neuwelt, E., Abbott, N.J., Abrey, L., Banks, W.A., Blakley, B., Davis, T., Engelhardt, B., Grammas, P., Nedergaard, M., Nutt, J., Pardridge, W., Rosenberg, G.A., Smith, Q., Drewes, L.R. Strategies to advance translational research into brain barriers. Lancet Neurol., 2008, 7, 84-96.
7. Pardridge, W.M. CNS drug design based on principles of bloodbrain barrier transport. J. Neurochem., 1998, 70, 1781-1792.
8. Pardridge, W.M. Drug targeting to the brain. Pharm. Res., 2007, 24, 1733-1744.
9. Wong, H.L., Wu, X.Y., Bendayan, R. Nanotechnological advances for the delivery of CNS therapeutics. Adv. Drug Deliv. Rev., 2011, doi: 10. 1016/j. addr. 2011. 10. 007.
10. Hawkins, B.T., Davis, T.P. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol. Rev., 2005, 57, 173-185.
11. Weksler, B.B., Subileau, E.A., Perriere, N., Charneau, P., Holloway, K., Leveque, M., Tricoire-Leignel, H., Nicotra, A., Bourdoulous, S., Turowski, P., Male, D.K., Roux, F., Greenwood, J., Romero, I.A., Couraud, P.O. Blood-brain barrier-specific properties of a human adult brain endothelial cell line. FASEB J., 2005, 19, 1872-1874.
12. Abbott, N.J. Astrocyte-endothelial interactions and blood-brain barrier permeability. J. Anat., 2002, 200, 629-638.
13. Abbott, N.J., Ronnback, L., Hansson, E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat. Rev. Neurosci., 2006, 7, 41-53.
14. Hawkins, B.T., Egleton, R.D. Pathophysiology of the blood-brain barrier: animal models and methods. Curr. Top. Dev. Biol., 2008, 80, 277-309.
15. Pardridge, W.M. Blood-brain barrier drug targeting: the future of brain drug development. Mol. Interv., 2003, 3,105-151.
16. Stewart, P.A. Endothelial vesicles in the blood-brain barrier: are they related to permeability? Cell. Mol. Neurobiol., 2000, 20, 149-163.
17. Oldendorf, W.H., Cornford, M.E., Brown, W.J. The large apparent work capability of the blood-brain barrier: a study of the mitochondrial content of capillary endothelial cells in brain and other tissues of the rat. Ann. Neurol., 1977, 1, 409-417.
18. Persidsky, Y., Ramirez, S.H., Haorah, J., Kanmogne, G.D. Bloodbrain barrier: structural components and function under physiologic and pathologic conditions. J. Neuroimmune. Pharmacol., 2006, 1, 223-236.
19. Ramsauer, M., Kunz, J., Krause, D., Dermietzel, R. Regulation of a blood-brain barrier-specific enzyme expressed by cerebral pericytes (pericytic amino peptidase N/pAPN) under cell culture conditions. J. Cereb. Blood Flow Metab., 1998, 18, 1270-1281.
20. Ramsauer, M., Krause, D., Dermietzel, R. Angiogenesis of the blood-brain barrier in vitro and the function of cerebral pericytes. FASEB J., 2002, 16, 1274-1276.
21. Dohgu, S., Takata, F., Yamauchi, A., Nakagawa, S., Egawa, T., Naito, M., Tsuruo, T., Sawada, Y., Niwa, M., Kataoka, Y. Brain pericytes contribute to the induction and up-regulation of bloodbrain barrier functions through transforming growth factor-beta production. Brain Res., 2005, 1038, 208-215.
22. Pardridge, W.M. Molecular biology of the blood-brain barrier. Mol. Biotechnol., 2005, 30, 57-70.
23. Bendayan, R., Lee, G., Bendayan, M. Functional expression and localization of p-glycoprote in at the blood brain barrier. Microsc. Res. Tech., 2002, 57, 365-380.
24. Deeken, J.F., Loscher, W. The blood-brain barrier and cancer: transporters, treatment, and Trojan horses. Clin. Cancer Res., 2007, 13, 1663-1674.
25. Ronaldson, P.T., Persidsky, Y., Bendayan, R. Regulation of ABC membrane transporters in glial cells: relevance to the pharmacotherapy of brain HIV-1 Infection. Glia, 2008, 56, 1711-1735.
26. Wekerle, H. Immune protection of the brain-efficient and delicate. J. Infect. Dis., 2002, 186, 140-144.
27. Rip, J., Schenk, G.J., de Boer, A.G. Differential receptor-mediated drug targeting to the diseased brain. Expert Opin. Drug Deliv., 2009, 6, 227-237.
28. Pathan, S.A., Iqbal, Z., Zaidi, S.M., Talegaonkar, S., Vohra, D., Jain, G.K., Azeem, A., Jain, N., Lalani, J.R., Khar, R.K., Ahmad, F.J. CNS drug delivery systems: novel approaches. Recent Pat. Drug Deliv. Formul., 2009, 3, 71-89.
29. Cohen, B.E., Bangham, A.D. Diffusion of small non-electrolytes across liposome membranes. Nature, 1972, 236, 173-174.
30. Liu, X., Tu, M., Kelly, R.S., Chen, C., Smith, B.J. Development of a computational approach to predict blood-brain barrier permeability. Drug Metab. Dispos., 2004, 32, 132-139.
31. Camenisch, G., Alsenz, J., van de Waterbeemd, H., Folkers, G. Estimation of permeability by passive diffusion through Caco-2 cell monolayers using the drugs' lipophilicity and molecular weight. Eur. J. Pharm. Sci., 1998, 6, 317-324.
32. van de Waterbeemd, H., Camenisch, G., Folkers, G., Chretien, J.R., Raevsky, O.A. Estimation of blood-brain barrier crossing of drugs using molecular size and shape, and H-bonding descriptors. J. Drug Target, 1998, 6, 151-165.
33. Clark, D.E. In silico prediction of blood-brain barrier permeation. Drug Discov. Today, 2003, 8, 927-933.
34. Pardridge, W.M. Biopharmaceutical drug targeting to the brain. J. Drug Target, 2010, 18, 157-167.
35. Kis, O., Robillard, K., Chan G.N., Bendayan, R. The complexities of antiretroviral drug-drug interactions: role of ABC and SLC transporters. Trends Pharmacol. Sci., 2010, 31, 22-35.
36. Bodor, N., Buchwald, P. Brain-targeted drug delivery: experiences to date. Am. J. Drug Target, 2003, 1, 13-26.
37. Kandimalla, K.K., Donovan, M.D. Transport of hydroxyzine and triprolidine across bovine olfactory mucosa: role of passive diffusion in the direct nose-to-brain uptake of small molecules. Int. J. Pharm., 2005, 302, 133-144
38. Karasova, J.Z., Pohanka, M., Musilek, K., Zemek, F., Kuca, K. Passive diffusion of acetylcholinesterase oxime reactivators through the blood-brain barrier: Influence of molecular structure. Toxicol. In Vitro, 2012, 24, 1838-1844.
39. Gaillard, P.J., Visser, C.C., de Boer A.G. Targeted delivery across the blood-brain barrier. Expert Opin. Drug Deliv., 2005, 2, 299-309.
40. Jonker, J.W., Smit, J.W., Brinkhuis, R.F., Maliepaard, M., Beijnen, J.H., Schellens, J.H.M., Schinkel, A.H. Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. JNCI, 2000, 92, 1651-1656.
41. Liu, Y.C., Liu, H.Y., Yang, H.W., Wen, T., Shang, Y., Liu, X.D., Xie, L., Wang, G.J. Impaired expression and function of breast cancer resistance protein (Bcrp) in brain cortex of streptozocininduced diabetic rats. Biochem. Pharmacol., 2007, 74, 1766-1772.
42. Sakata, A., Tamai, I., Kawazu, K., Deguchi, Y., Ohnishi, T., Saheki, A., Tsuji, A. In vivi evidence for ATP-dependent and Pglycoprotein-mediated transport of cyclosporin A at the bloodbrain barrier. Biochem. Pharmacol., 1994, 48, 1989-1992.
43. Nies, A.T., Jedlitschky, G., König, J., Herold-Mende, C., Steiner, H.H., Schmitt, H.-P., Keppler, D. Expression and immunolocalization of the multidrug resistance proteins, MRP1-MRP6 (ABCC1-ABCC6), in human brain. Neuroscience, 2004, 129, 349-360.
44. Huang, Y., Sadee, W. Membrane transporters and channels in chemoresistance and sensitivity of tumor cells. Cancer Lett., 2006, 239, 168-82.
45. Demeule, M., Régina, A., Jodoin, J., Laplante, A., Dagenais, C., Berthelet, F., Moghrabi, A., Béliveau, R. Drug transport to the brain: key roles for the efflux pump P-glycoprotein in the bloodbrain barrier. Vas. Pharmacol., 2002, 38, 339-348.
46. Polli, J.W., Olson, K.L., Chism, J.P., John-Williams, L.S., Yeager, R.L., Woodard, S.M., Otto, V., Castellino, S., Demby, V.E. An unexpected synergist role of P-glycoprotein and breast cancer resistance protein on the central nervous system penetration of the tyrosine kinase inhibitor lapatinib (N-{3-chloro-4-[(3-fluorobenzyl) oxy] phenyl}-6-[5-({[2-(methylsulfonyl) ethyl] amino} methyl)-2-furyl]-4-quinazolinamine; GW572016). Drug Metab. Dispos., 2009, 37, 439-442.
47. Kruh, G.D., Belinsky, M.G. The MRP family of drug efflux pumps. Oncogene, 2003, 22, 7537-7552.
48. Roberts, L.M., Black, D.S., Raman, C., Woodford, K., Zhou, M., Haggerty, J.E., Yan, A.T., Cwirla, S.E., Grindstaff, K.K. Subcellular localization of transporters along the rat blood-brain barrier and blood-cerebral-spinal fluid barrier by in vivo biotinylation. Neuroscience, 2008, 155, 423-438.
49. Loscher, W., Potschka, H. Drug resistance in brain diseases and the role of drug efflux transporters. Nat. Rev. Neurosci., 2005, 6, 591-602.
50. Hediger, M.A., Romero, M.F., Peng, J.B., Rolfs, A., Takanaga, H., Bruford, E.A. The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteins: Introduction. Pflugers Arch, 2004, 447, 465-468.
51. Ito, K., Suzuki, H., Horie, T., Sugjyama, Y. Apical/basolateral surface expression of drug transporters and its role in vectorial drug transport. Pharm. Res., 2005, 22, 1559-1577.
52. de Boer, A.G., Gaillard, P.J. Drug targeting to the brain. Annu. Rev. Pharmacol. Toxicol., 2007, 47, 323-355.
53. Pardridge, W.M. Blood-brain barrier biology and methodology. J. Neurovirol., 1999, 5, 556-569.
54. Moos, T., Morgan, E.H. Transferrin and transferrin receptor function in brain barrier systems. Cell Mol. Neurobiol., 2000, 20, 77-95.
55. Derossi, D., Joliot, A.H., Chassaing, G., Prochiantz, A. The third helix of the antennapedia homeodomain translocates through biological membranes. J. Biol. Chem., 1994, 269, 10444-10450.
56. Mäe, M., Langel, U. Cell-penetrating peptides as vectors for peptide, protein and oligonucleotide delivery. Curr. Opin. Pharmacol., 2006, 6, 509-514.
57. Vivés, E., Brodin, P., Lebleu, B. A truncated HIV-1 Tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus. J. Biol. Chem., 1997, 272, 16010-16017.
58. Pooga, M., Hällbrink, M., Zorko, M., Langel, U. Cell penetration by transportan. FASEB J., 1998, 12, 67-77.
59. Rothbard, J.B., Garlington, S., Lin, Q., Kirschberg, T., Kreider, E., McGrane, P.L., Wender, P.A., Khavari, P.A. Conjugation of arginine oligomers to cyclosporin A facilitates topical delivery and inhibition of inflammation. Nat. Med., 2000, 6, 1253-1257.
60. El-Andaloussi, S., Holm, T., Langel, U. Cell-penetrating peptides: mechanisms and applications. Curr. Pharm, Des., 2005, 11, 3597-3611.
61. Snyder, E.L., Dowdy, S.F. Recent advances in the use of protein transduction domains for the delivery of peptides, proteins and nucleic acids in vivo. Expert. Opin. Drug Deliv., 2005, 2, 43-51.
62. Heitz, F., Morris, M.C., Divita, G. Twenty years of cellpenetrating peptides: from molecular mechanisms to therapeutics. Br. J. Pharmacol., 2009, 157, 195-206.
63. Fonseca, S.B., Pereira, M.P., Kelley, S.O. Recent advances in the use of cell-penetrating peptides for medical and biological applications. Adv. Drug Deliver. Rev., 2009, 61, 953-964.
64. Gabathuler R. Development of new peptide vectors for the transport of therapeutic across the blood-brain barrier. Ther. Deliver., 2010, 1, 571-586.
65. Gallo, G. Making proteins into drugs: assisted delivery of proteins and peptides into living neurons. Methods Cell Biol., 2003, 71, 325-338.
66. Kumar, P., Wu, H.Q., McBride, J.L., Jung, K-E., Kim, M.H., Davidson, B.L., Lee, S.K., Shankar, P., Manjunath, N. Transvascular delivery of small interfering RNA to the central nervous system. Nature, 2007, 448, 39-43.
67. Cai, B., Lin, Y., Xue, X.H., Fang, L., Wang, N., Wu, Z.Y. TATmediated delivery of neuroglobin protects against focal cerebral ischemia in mice. Exp. Neurol., 2011, 227, 224-231.
68. Luo, D., Saltzman, M. Synthetic DNA delivery systems. Nat. Biotechnol., 2000, 18, 33-37.
69. Herce, H.D., Garcia, A.E. Cell penetrating peptides: how do they do it? J. Biol. Phys., 2007, 33, 345-356.
70. Lundberg, M., Johansson, M. Is VP22 nuclear homing an artifact? Nat. Biotechnol., 2001, 19, 713-771.
71. Frankel, A.D., Pabo, C.O. Cellular uptake of the tat protein from human immunodeficiency virus. Cell, 1988, 55, 1189-1119.
72. Plenat, T., Deshayes, S., Boichot, S., Milhiet, P. E., Cole, R., Heitz, F., Grimellec, C.L. Interaction of primary amphipathic cellpenetrating peptides with phospholipid-supported monolayers. Langmuir, 2004, 20, 9255-9261.
73. Deshayes, S., Gerbal-Chaloin, S., Morris, M.C., Aldrian-Herrada, G., Charnet, P., Divita, G., Heitz, F. On the mechanism of nonendosomial peptide-mediated cellular delivery of nucleic acids. Biochim. Biophys. Acta., 2004, 1667, 141-114.
74. Theisen, D.M., Pongratz, C., Wiegmann, K., Rivero, F., Krut, O., Krönke, M. Targeting of HIV-1 Tat traffic and function by transduction-competent single chain antibodies. Vaccine, 2006, 24, 3127-3136.
75. Cao, L., Si, J., Wang, W., Zhao, X., Yuan, X., Zhu, H., Wu, X., Zhu, J., Shen, G. Intracellular localization and sustained prodrug cell killing activity of TAT-HSVTK fusion protein in hepatocelullar carcinoma cells. Mol. Cells, 2006, 21, 104-111.
76. Schwarze, S.R., Ho, A., Vocero-Akbani, A., Dowdy, S.F. In vivo protein transduction: delivery of a biologically active protein into the mouse. Science, 1999, 285, 1569-1572.
77. Cao, G., Pei, W., Ge, H., Liang, Q., Luo, Y., Sharp, F.R., Lu, A., Ran, R., Graham, S.H., Chen, J. In vivo delivery of a Bcl-xL fusion protein containing the TAT protein transduction domain protects against ischemic brain injury and neuronal apoptosis. J. Neurosci., 2002, 22, 5423-5431.
78. Hirt, L., Badaut, J., Thevenet, J., Granziera, C., Regli, L., Maurer, F., Bonny, C., Bogousslavsky, J. D-JNKI1, a cell-penetrating c-Jun-N-terminal kinase inhibitor, protects against cell death in severe cerebral ischemia. Stroke, 2004, 35, 1738-1743.
79. Aarts, M., Liu, Y.T., Liu, L.D., Besshoh, S., Arundine, M., Gurd, J.W., Wang, Y.T., Salter, M.W., Tymianski, M. Treatment of ischemic brain damage by perturbing NMDA receptor-PSD-95 protein interactions. Science, 2002, 298, 846-850.
80. Kilic, E., Kilic, U., Hermann, D.M. TAT-GDNF in neurodegeneration and ischemic stroke. CNS Drug Rev., 2005, 11, 369-378.
81. Fu, A., Wang, Y., Zhan, L., Zhou, R. Targeted delivery of proteins into the central nervous system mediated by rabies virus glycoprotein-derived peptide. Pharm. Res. 2012, 29, 1562-1569.
82. Xiang, L., Zhou, R., Fu, A., Xu, X., Huang, Y., Hu, C. Targeted delivery of large fusion protein into hippocampal neurons by systemic administration. J. Drug Target. 2011, 19, 632-636.
83. Jo, D., Liu, D., Yao, S., Collins, R.D., Hawiger, J. Intracellular protein therapy with SOCS3 inhibits inflammation and apoptosis. Nat. Med., 2005, 11, 892-898.
84. Liu, Z.H., Li, M.Y., Cui, D.F., Fei, J. Macro-branched cellpenetrating peptide design for gene delivery. J. Control Release, 2005, 102, 699-710.
85. Rudolph, C., Plank, C., Lausier, J., Schillinger, U., Müller, R.H., Rosenecker, J. Oligomers of the arginine-rich motif of the HIV-1 TAT protein are capable of transferring plasmid DNA into cells. J. Biol. Chem., 2003, 278, 11411-11418.
86. Knight, A., Carvajal, J., Schneider, H., Coutelle, C., Chamberlain, S., Fairweather, N. Non-viral neuronal gene delivery mediated by the HC fragment of tetanus toxin. Eur. J. Biochem., 1999, 259, 762-769.
87. Lo, S.L., Wang, S. An endosomolytic Tat peptide produced by incorporation of histidine and cysteine residues as a nonviral vector for DNA transfection. Biomaterials, 2008, 29, 2408-2414.
88. Sawant R.R.; Torchilin V.P. Intracellular Delivery: A Multifunctional and Modular Approach. In: Intracellular delivery; Prokop A., Ed.; Springer Science + Business Media: Nashville, 2011; Vol. 1, pp. 212-213.
89. Li, W.J., Szoke, F.C. Lipid-based nanoparticles for nucleic acid delivery. Pharm. Res., 2007, 24, 438-449.
90. Suk, J.S., Suh, J., Choy, K., Lai, S.K., Hanes, J. Gene delivery to differentiated neurotypic cells with RGD and HIV Tat peptide functionalizaed polymeric nanoparticles. Biomaterials, 2006, 27, 5143-5150.
91. Eguchi, A., Meade, B.R., Chang, Y.C., Fredrickson, C.T., Willert, K., Puri, N., Dowdy, S.F. Efficient siRNA delivery into primary cells by a peptide transduction domain-dsRNA binding domain fusion protein. Nat. Biotechnol., 2009, 27, 567-571.
92. Meade, B.R., Dowdy, S.F. Enhancing the cellular uptake of siRNA duplexes following noncovalent packaging with protein transduction domain peptides. Adv. Drug Deliv. Rev., 2008, 60, 530-536.
93. Said Hassane, F., Saleh, A.F., Abes, R., Gait, M.J., Lebleu, B. Cell penetrating peptides: overview and applications to the delivery of oligonucleotides. Cell. Mol. Life Sci., 2010, 67, 715-726.
94. Lingor, P., Bahr, M. Targeting neurological disease with RNAi. Mol. Biosyst., 2007, 3, 773-780.
95. Ralph, G.S., Mazarakis, N.D., Azzouz, M. Therapeutic gene silencing in neurological disorders, using interfering RNA. J. Mol. Med., 2005, 83, 413-419.
96. Mathupala, S.P. Delivery of small-interfering RNA (siRNA) to the brain. Expert Opin. Ther. Pat., 2009, 19, 137-140.
97. Alvarez-Erviti, L., Seow, Y., Yin, H.F., Betts, C., Lakhal, S., Wood, M.J.A. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011, 29, 341-345.
98. Hwang, D.W., Son, S., Jang, J., Youn, H., Lee, S., Lee, D., Lee, YS., Jeong, J.M., Kim, W.J., Lee, D.S. A brain-targeted rabies virus glycoprotein-disulfide linked PEI nanocarrier for delivery of neurogenic microRNA. Biomaterials, 2011, 32, 4968-4975.
99. Davidson, T.J., Harel, S., Arboleda, V.A., Prunell, G.F., Shelanski, M.L., Greene, L.A., Tory, C.M. Highly efficient small interfering RNA delivery to primary mammalian neurons induces MicroRNAlike effects before mRNA degradation. J. Neurosci., 2004, 24, 10040-10046.
100. Corey, D.R., Abrams, J.M. Morpholino antisense oligonucleotides: tolls for investigating vertebrate development. Genome Biol., 2001, 2, reviews 1015.1-1015.3.
101. Du, L.T., Kayali, R., Bertoni, C., Fike, F., Hu, H.L., Iversen, P.L., Gatti, R.A. Arginine-rich cell-penetrating peptide dramatically enhances AMO-mediated ATM aberrant splicing correction and enables delivery to brain and cerebellum. Hum. Mol. Genet., 2011, 20, 3151-3160.
102. Caille, I., Allinquant, B., Dupont, E., Bouillot, C., Langer, A., Muller, U., Prochiantz, A. Soluble form of amyloid precursor protein regulates proliferation of progenitors in the adult subventricular zone. Development, 2004, 131, 2173-2181.
103. Morishita, R., Gibbons, G.H., Horiuchi, M., Ellison, K.E., Nakama, M., Zhang, L., Kaneda, Y., Ogihara, T. and Dzau, V.J. A gene therapy strategy using a transcription factor decoy of the E2F binding site inhibits smooth muscle proliferation in vivo. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 5855-5859.
104. Fisher, L., Soomets, U., Cortes, T.V., Chilton, L., Jiang, Y., Langel, Ü., Iverfeldt, K. Cellular delivery of a double-stranded oligonucleotide NF-κB decoy by hybridization to complementary PNA linked to a cell-penetrating peptide. Gene Ther., 2004, 11, 1264-1272.
105. Liu, L., Guo, K., Lu, J., Venkatraman, S.S., Luo, D., Moochhala, S., Yang, Y.Y. Biologically active core/shell nano-particles selfassembled from cholesterol-terminated PEG-TAT for drug delivery across the blood-brain barrier. Biomaterials, 2008, 29, 1509-1517.
106. Kanazawa, T., Taki, H., Tanaka, K., Takashima, Y., Okada, H. Cell-penetrating peptide-modified block copolymer micelles promote direct brain delivery via intranasal administration. Pharm. Res., 2011, 28, 2130-2139.
107. Orthmann, A., Fichtner, I., Zeisig, R. Improving the transport of chemotherapeutic drugs across the blood-brain barrier. Expert Rev. Clin. Pharmacol., 2011, 4, 477-490.
108. Adenot, M., Merida, P., Lahana, R. Applications of a blood-brain barrier technology platform to predict CNS penetration of various chemotherapeutic agents. 2. Cationic peptide vectors for brain delivery. Pharmacology, 2007, 53, 73-76.
109. Rousselle, C., Clair, P., Smirnova, M., Kolesnikov, Y., Pasternak, G.W., Gac-Breton, S., Rees, A.R., Scherrmann, J.M., Temsamani, J. Improved brain uptake and pharmacological activity of dalargin using a peptide-vector-mediated strategy. J. Pharmacol. Exp. Ther., 2003, 306, 371-376.
110. Drin, G., Cottin, S., Blanc, E., Rees, A.R., Temsamani, J. Studies on the intern alisation mechanism of cationic cell-penetrating peptides. J. Biol. Chem., 2003, 278, 31192-31201.
111. Rousselle, C., Clair, P., Lefauconnier, J. M., Kaczorek, M., Scherrmann, J. M., Temsamani, J. New advances in the transport of doxorubicin through the blood-brain barrier by a peptide vectormediated strategy. Mol. Pharmacol., 2000, 57, 679-686.
112. Demeule, M., Currie, J.C., Bertrand, Y., Ché, C., Nguyen, T., Régina, A., Gabathuler, R., Castaigne, J.P., Béliveau, R. Involvement of the low-density lipoprotein receptor-related protein in the transcytosis of the brain delivery vector Angiopep-2. J. Neurochem., 2008, 106, 1534-1544.
113. Ché, C., Yang, G., Thiot, C., Lacoste, M.C., Currie, J.C., Demeule, M., Régina, A., Béliveau, R., Castaigne, J.P. New angiopepmodified doxorubin (ANG 1007) and etoposide (ANG 1009) chemotherapeutics with increased brain penetration. Pharmacol., 2010, 53, 2814-2824.
114. Ren, J., Shen, S., Wang, D., Xi, Z., Guo, L., Pang, Z., Qian, Y., Sun, X., Jiang, X. The targeted delivery of anticancer drugs to brain glioma by PEGylated oxidized multi-walled carbon nanotubes modified with angiopep-2. Biomaterials, 2012, 33, 3324-3333.
115. Kurzrock, R., Gabrail, N., Chandhasin, C., Moulder, S., Smith, C., Brenner, A., Sankhala, K., Mita, A., Elian, K., Bouchard, D., Sarantopoulos, J. Safety, pharmacokinetics, and activity of GRN1005, a novel conjugate of angiopep-2, a peptide facilitating brain penetration, and paclitaxel, in patients with advanced solid tumors. Mol. Cancer Ther., 2012, 11, 308-316.
116. Bertrand, Y., Currie, J.C., Poirier, J., Demeule, M., Abulrob, A., Fatehi, D., Stanimirovic, D., Sartelet, H., Castaigne, J.P., Béliveau, R. Influence of glioma tumour microenvironment on the transport of ANG1005 via low-density lipoprotein receptor-related protein 1. Br. J. Cancer, 2011, 105, 1697-1707.
117. Santra, S., Yang, H., Stanley, J.T., Holloway, P.H., Moudgil, B.M., Walter, G., Mericle, R.A. Rapid and effective labeling of brain tissue using TAT-conjugated CdS:Mn/ZnS quantum dots. Chem. Commun. (Camb.), 2005, 3144-3146.
118. Santra, S., Yang, H., Holloway, P.H., Stanley, J.T., Mericle, R.A. Synthesis of water-dispersible fluorescent, radio-opaque, and paramagnetic CdS:Mn/ZnS quantum dots: a multifunctional probe for bioimaging. J. Am. Chem. Soc., 2005, 127, 1656-1657.
119. Liu, L., Venkatraman, S.S., Yang, Y.Y., Guo, K., Lu, J., He, B., Moochhala, S., Kan, L. Polymeric micelles anchored with TAT for delivery of antibiotics across the blood-brain barrier. Biopolymers, 2008, 90, 617-623.
120. Wang, H., Xu, K., Liu, L., Tan, J.P., Chen, Y., Li, Y., Fan, W., Wei, Z., Sheng, J., Yang, Y.Y., Li, L. The efficacy of selfassembled cationic antimicrobial peptide nanoparticles against Cryptococcus neoformans for the treatment of meningitis. Biomaterials, 2010, 31, 2874-2881.
121. Qin, Y., Chen, H., Yuan, W., Kuai, R., Zhang, Q., Xie, F., Zhang, L., Zhang, Z., Liu, J., He, Q. Liposome formulated with TATmodified cholesterol for enhancing the brain delivery. Int. J. Pharm., 2011, 420, 304-312.
122. Tosi, G., Costantino, L., Rivasi, F., Ruozi, B., Leo, E., Vergoni, A.V., Tacchi, R., Bertolini, A., Vandelli, M.A., Forni, F. Targeting the central nervous system: in vivo experiments with peptidederivatized nanoparticles loaded with loperamide and rhodamine-123. J. Control. Release, 2007, 122, 1-9.
123. Vergoni, A.V., Tosi, G., Tacchi, R., Vandelli, M.A., Bertolini, A., Costantino, L. Nano-particles as drug delivery agents specific for CNS: in vivo biodistribution. Nano-medicine, 2009, 5, 369-377.
124. Ke, W.L., Shao, K., Huang, R.Q., Han, L., Liu, Y., Li, J.F., Kuang, Y.Y., Ye, L.Y., Lou, J.N., Jiang, C. Gene delivery targeted to the brain using an Angiopep-conjugated plyethyleneglycol-modified polyamidoamine dendrimer. Biomaterials, 2010, 30, 6976-6985.