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Erschienen in: Journal of Neurology 3/2016

01.03.2016 | Review

Strategies to target drugs to gliomas and CNS metastases of solid tumors

verfasst von: B. Milojkovic Kerklaan, O. van Tellingen, A. D. R. Huitema, J. H. Beijnen, W. Boogerd, J. H. M. Schellens, D. Brandsma

Erschienen in: Journal of Neurology | Ausgabe 3/2016

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Abstract

The treatment for central nervous system metastases of solid tumors and gliomas is limited as the blood–brain barrier (BBB) is an obstacle to systemic therapy. Here, we review the physiochemical properties of the BBB and both current and new drug strategies to penetrate brain tumors. We focus on targeting receptor- or carrier-mediated transport mechanisms over the BBB used by drug conjugates, nanoparticles, polymer-based nanocarriers, siRNA, and antibodies.
Literatur
2.
Zurück zum Zitat Wrensch M, Minn Y, Chew T, Bondy M, Berger MS (2002) Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro-Oncol 4:278–299PubMedPubMedCentral Wrensch M, Minn Y, Chew T, Bondy M, Berger MS (2002) Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro-Oncol 4:278–299PubMedPubMedCentral
3.
Zurück zum Zitat Lim E, Lin NU (2014) Updates on the management of breast cancer brain metastases. Oncology (Williston Park) 28:572–578 Lim E, Lin NU (2014) Updates on the management of breast cancer brain metastases. Oncology (Williston Park) 28:572–578
4.
Zurück zum Zitat Stupp R et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996PubMedCrossRef Stupp R et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996PubMedCrossRef
6.
Zurück zum Zitat Batchelor TT et al (2013) Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. J Clin Oncol 31:3212–3218PubMedPubMedCentralCrossRef Batchelor TT et al (2013) Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. J Clin Oncol 31:3212–3218PubMedPubMedCentralCrossRef
7.
Zurück zum Zitat Tonder M et al (2014) Addition of lomustine for bevacizumab-refractory recurrent glioblastoma. Acta Oncol 53:1436–1440PubMedCrossRef Tonder M et al (2014) Addition of lomustine for bevacizumab-refractory recurrent glioblastoma. Acta Oncol 53:1436–1440PubMedCrossRef
8.
9.
Zurück zum Zitat Posner JB (1977) Management of central nervous system metastases. Semin Oncol 4:81–91PubMed Posner JB (1977) Management of central nervous system metastases. Semin Oncol 4:81–91PubMed
10.
Zurück zum Zitat Sperduto PW et al (2012) Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol 30:419–425PubMedPubMedCentralCrossRef Sperduto PW et al (2012) Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol 30:419–425PubMedPubMedCentralCrossRef
11.
Zurück zum Zitat Le Rhun E et al (2013) A retrospective case series of 103 consecutive patients with leptomeningeal metastasis and breast cancer. J Neurooncol 113:83–92PubMedCrossRef Le Rhun E et al (2013) A retrospective case series of 103 consecutive patients with leptomeningeal metastasis and breast cancer. J Neurooncol 113:83–92PubMedCrossRef
12.
Zurück zum Zitat Chamberlain M et al (2014) Leptomeningeal metastasis: a Response Assessment in Neuro-Oncology critical review of endpoints and response criteria of published randomized clinical trials. Neuro-oncol Chamberlain M et al (2014) Leptomeningeal metastasis: a Response Assessment in Neuro-Oncology critical review of endpoints and response criteria of published randomized clinical trials. Neuro-oncol
13.
Zurück zum Zitat Le Rhun E, Taillibert S, Chamberlain M (2013) Carcinomatous meningitis: leptomeningeal metastases in solid tumors. Surg Neurol Int 4:265–288 Le Rhun E, Taillibert S, Chamberlain M (2013) Carcinomatous meningitis: leptomeningeal metastases in solid tumors. Surg Neurol Int 4:265–288
15.
Zurück zum Zitat Wick W et al (2010) Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol 28:1168–1174PubMedPubMedCentralCrossRef Wick W et al (2010) Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol 28:1168–1174PubMedPubMedCentralCrossRef
16.
Zurück zum Zitat Sperduto PW et al (2013) A phase 3 trial of whole brain radiation therapy and stereotactic radiosurgery alone versus WBRT and SRS with temozolomide or erlotinib for non-small cell lung cancer and 1 to 3 brain metastases: radiation Therapy Oncology Group 0320. Int J Radiat Oncol Biol Phys 85:1312–1318PubMedPubMedCentralCrossRef Sperduto PW et al (2013) A phase 3 trial of whole brain radiation therapy and stereotactic radiosurgery alone versus WBRT and SRS with temozolomide or erlotinib for non-small cell lung cancer and 1 to 3 brain metastases: radiation Therapy Oncology Group 0320. Int J Radiat Oncol Biol Phys 85:1312–1318PubMedPubMedCentralCrossRef
17.
Zurück zum Zitat Stupp R et al (2010) Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosed glioblastoma. J Clin Oncol 28:2712–2718PubMedCrossRef Stupp R et al (2010) Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosed glioblastoma. J Clin Oncol 28:2712–2718PubMedCrossRef
18.
Zurück zum Zitat Zlokovic BV (2005) Neurovascular mechanisms of Alzheimer’s neurodegeneration. Trends Neurosci 28:202–208PubMedCrossRef Zlokovic BV (2005) Neurovascular mechanisms of Alzheimer’s neurodegeneration. Trends Neurosci 28:202–208PubMedCrossRef
19.
Zurück zum Zitat Nduom EK, Yang C, Merrill MJ, Zhuang Z, Lonser RR (2013) Characterization of the blood–brain barrier of metastatic and primary malignant neoplasms. J Neurosurg 119:427–433PubMedPubMedCentralCrossRef Nduom EK, Yang C, Merrill MJ, Zhuang Z, Lonser RR (2013) Characterization of the blood–brain barrier of metastatic and primary malignant neoplasms. J Neurosurg 119:427–433PubMedPubMedCentralCrossRef
20.
Zurück zum Zitat Lockman PR et al (2010) Heterogeneous blood–tumor barrier permeability determines drug efficacy in experimental brain metastases of breast cancer. Clin Cancer Res 16:5664–5678PubMedPubMedCentralCrossRef Lockman PR et al (2010) Heterogeneous blood–tumor barrier permeability determines drug efficacy in experimental brain metastases of breast cancer. Clin Cancer Res 16:5664–5678PubMedPubMedCentralCrossRef
22.
23.
Zurück zum Zitat Mathiisen TM, Lehre KP, Danbolt NC, Ottersen OP (2010) The perivascular astroglial sheath provides a complete covering of the brain microvessels: an electron microscopic 3D reconstruction. Glia 58:1094–1103PubMedCrossRef Mathiisen TM, Lehre KP, Danbolt NC, Ottersen OP (2010) The perivascular astroglial sheath provides a complete covering of the brain microvessels: an electron microscopic 3D reconstruction. Glia 58:1094–1103PubMedCrossRef
25.
Zurück zum Zitat Charest G, Sanche L, Fortin D, Mathieu D, Paquette B (2013) Optimization of the route of platinum drugs administration to optimize the concomitant treatment with radiotherapy for glioblastoma implanted in the Fischer rat brain. J Neurooncol 115:365–373PubMedCrossRef Charest G, Sanche L, Fortin D, Mathieu D, Paquette B (2013) Optimization of the route of platinum drugs administration to optimize the concomitant treatment with radiotherapy for glioblastoma implanted in the Fischer rat brain. J Neurooncol 115:365–373PubMedCrossRef
26.
Zurück zum Zitat Doolittle ND et al (2000) Safety and efficacy of a multicenter study using intraarterial chemotherapy in conjunction with osmotic opening of the blood–brain barrier for the treatment of patients with malignant brain tumors. Cancer 88:637–647PubMedCrossRef Doolittle ND et al (2000) Safety and efficacy of a multicenter study using intraarterial chemotherapy in conjunction with osmotic opening of the blood–brain barrier for the treatment of patients with malignant brain tumors. Cancer 88:637–647PubMedCrossRef
27.
Zurück zum Zitat Stamatovic SM, Keep RF, Andjelkovic AV (2008) Brain endothelial cell–cell junctions: how to ‘open’ the blood brain barrier. Curr Neuropharmacol 6:179–192PubMedPubMedCentralCrossRef Stamatovic SM, Keep RF, Andjelkovic AV (2008) Brain endothelial cell–cell junctions: how to ‘open’ the blood brain barrier. Curr Neuropharmacol 6:179–192PubMedPubMedCentralCrossRef
28.
Zurück zum Zitat Cote J et al (2010) Selective tumor blood–brain barrier opening with the kinin B2 receptor agonist [Phe(8)psi(CH(2)NH)Arg(9)]-BK in a F98 glioma rat model: an MRI study. Neuropeptides 44:177–185PubMedCrossRef Cote J et al (2010) Selective tumor blood–brain barrier opening with the kinin B2 receptor agonist [Phe(8)psi(CH(2)NH)Arg(9)]-BK in a F98 glioma rat model: an MRI study. Neuropeptides 44:177–185PubMedCrossRef
29.
Zurück zum Zitat Cuddapah VA, Turner KL, Seifert S, Sontheimer H (2013) Bradykinin-induced chemotaxis of human gliomas requires the activation of KCa3.1 and ClC-3. J Neurosci 33:1427–1440PubMedPubMedCentralCrossRef Cuddapah VA, Turner KL, Seifert S, Sontheimer H (2013) Bradykinin-induced chemotaxis of human gliomas requires the activation of KCa3.1 and ClC-3. J Neurosci 33:1427–1440PubMedPubMedCentralCrossRef
30.
Zurück zum Zitat Emerich DF, Dean RL, Osborn C, Bartus RT (2001) The development of the bradykinin agonist labradimil as a means to increase the permeability of the blood–brain barrier: from concept to clinical evaluation. Clin Pharmacokinet 40:105–123PubMedCrossRef Emerich DF, Dean RL, Osborn C, Bartus RT (2001) The development of the bradykinin agonist labradimil as a means to increase the permeability of the blood–brain barrier: from concept to clinical evaluation. Clin Pharmacokinet 40:105–123PubMedCrossRef
31.
Zurück zum Zitat Zhou L et al (2014) Bradykinin regulates the expression of claudin-5 in brain microvascular endothelial cells via calcium-induced calcium release. J Neurosci Res 92:597–606PubMedCrossRef Zhou L et al (2014) Bradykinin regulates the expression of claudin-5 in brain microvascular endothelial cells via calcium-induced calcium release. J Neurosci Res 92:597–606PubMedCrossRef
32.
Zurück zum Zitat Chi OZ, Wei HM, Lu X, Weiss HR (1996) Increased blood–brain permeability with hyperosmolar mannitol increases cerebral O2 consumption and O2 supply/consumption heterogeneity. J Cereb Blood Flow Metab 16:327–333PubMedCrossRef Chi OZ, Wei HM, Lu X, Weiss HR (1996) Increased blood–brain permeability with hyperosmolar mannitol increases cerebral O2 consumption and O2 supply/consumption heterogeneity. J Cereb Blood Flow Metab 16:327–333PubMedCrossRef
33.
Zurück zum Zitat Rodriguez A, Tatter S, Debinski W (2015) Neurosurgical techniques for disruption of the blood–brain barrier for glioblastoma treatment. Pharmaceutics 7:175–187PubMedPubMedCentralCrossRef Rodriguez A, Tatter S, Debinski W (2015) Neurosurgical techniques for disruption of the blood–brain barrier for glioblastoma treatment. Pharmaceutics 7:175–187PubMedPubMedCentralCrossRef
34.
Zurück zum Zitat Shin BJ, Burkhardt JK, Riina HA, Boockvar JA (2012) Superselective intra-arterial cerebral infusion of novel agents after blood–brain disruption for the treatment of recurrent glioblastoma multiforme: a technical case series. Neurosurg Clin N Am 23:323–329PubMedCrossRef Shin BJ, Burkhardt JK, Riina HA, Boockvar JA (2012) Superselective intra-arterial cerebral infusion of novel agents after blood–brain disruption for the treatment of recurrent glioblastoma multiforme: a technical case series. Neurosurg Clin N Am 23:323–329PubMedCrossRef
35.
Zurück zum Zitat Liu L-B et al (2015) Bradykinin increased the permeability of BTB via NOS/NO/ZONAB-mediating down-regulation of claudin-5 and occludin. Biochem Biophys Res Commun 464:118–125PubMedCrossRef Liu L-B et al (2015) Bradykinin increased the permeability of BTB via NOS/NO/ZONAB-mediating down-regulation of claudin-5 and occludin. Biochem Biophys Res Commun 464:118–125PubMedCrossRef
36.
Zurück zum Zitat Prados MD et al (2003) A randomized, double-blind, placebo-controlled, phase 2 study of RMP-7 in combination with carboplatin administered intravenously for the treatment of recurrent malignant glioma. Neuro-oncology 5:96–103PubMedPubMedCentral Prados MD et al (2003) A randomized, double-blind, placebo-controlled, phase 2 study of RMP-7 in combination with carboplatin administered intravenously for the treatment of recurrent malignant glioma. Neuro-oncology 5:96–103PubMedPubMedCentral
38.
Zurück zum Zitat Kirson ED et al (2004) Disruption of cancer cell replication by alternating electric fields. Cancer Res 64:3288–3295PubMedCrossRef Kirson ED et al (2004) Disruption of cancer cell replication by alternating electric fields. Cancer Res 64:3288–3295PubMedCrossRef
39.
Zurück zum Zitat Sloan AE et al (2013) Results of the NeuroBlate System first-in-humans Phase I clinical trial for recurrent glioblastoma: clinical article. J Neurosurg 118:1202–1219PubMedCrossRef Sloan AE et al (2013) Results of the NeuroBlate System first-in-humans Phase I clinical trial for recurrent glioblastoma: clinical article. J Neurosurg 118:1202–1219PubMedCrossRef
40.
Zurück zum Zitat Sheikov N, McDannold N, Vykhodtseva N, Jolesz F, Hynynen K (2004) Cellular mechanisms of the blood–brain barrier opening induced by ultrasound in presence of microbubbles. Ultrasound Med Biol 30:979–989PubMedCrossRef Sheikov N, McDannold N, Vykhodtseva N, Jolesz F, Hynynen K (2004) Cellular mechanisms of the blood–brain barrier opening induced by ultrasound in presence of microbubbles. Ultrasound Med Biol 30:979–989PubMedCrossRef
41.
Zurück zum Zitat Hynynen K, McDannold N, Sheikov NA, Jolesz FA, Vykhodtseva N (2005) Local and reversible blood–brain barrier disruption by noninvasive focused ultrasound at frequencies suitable for trans-skull sonications. Neuroimage 24:12–20PubMedCrossRef Hynynen K, McDannold N, Sheikov NA, Jolesz FA, Vykhodtseva N (2005) Local and reversible blood–brain barrier disruption by noninvasive focused ultrasound at frequencies suitable for trans-skull sonications. Neuroimage 24:12–20PubMedCrossRef
42.
Zurück zum Zitat Liu H-L, Fan C-H, Ting C-Y, Yeh C-K (2014) Combining microbubbles and ultrasound for drug delivery to brain tumors: current progress and overview. Theranostics 4:432–444PubMedPubMedCentralCrossRef Liu H-L, Fan C-H, Ting C-Y, Yeh C-K (2014) Combining microbubbles and ultrasound for drug delivery to brain tumors: current progress and overview. Theranostics 4:432–444PubMedPubMedCentralCrossRef
43.
Zurück zum Zitat Jenne JW (2015) Non-invasive transcranial brain ablation with high-intensity focused ultrasound. Front Neurol Neurosci 36:94–105PubMedCrossRef Jenne JW (2015) Non-invasive transcranial brain ablation with high-intensity focused ultrasound. Front Neurol Neurosci 36:94–105PubMedCrossRef
44.
Zurück zum Zitat Schober R, Bettag M, Sabel M, Ulrich F, Hessel S (1993) Fine structure of zonal changes in experimental Nd:YAG laser-induced interstitial hyperthermia. Lasers Surg Med 13:234–241PubMedCrossRef Schober R, Bettag M, Sabel M, Ulrich F, Hessel S (1993) Fine structure of zonal changes in experimental Nd:YAG laser-induced interstitial hyperthermia. Lasers Surg Med 13:234–241PubMedCrossRef
45.
Zurück zum Zitat Hawasli AH, Kim AH, Dunn GP, Tran DD, Leuthardt EC (2014) Stereotactic laser ablation of high-grade gliomas. Neurosurg Focus 37:E1PubMedCrossRef Hawasli AH, Kim AH, Dunn GP, Tran DD, Leuthardt EC (2014) Stereotactic laser ablation of high-grade gliomas. Neurosurg Focus 37:E1PubMedCrossRef
46.
Zurück zum Zitat Golberg A, Yarmush ML (2013) Nonthermal irreversible electroporation: fundamentals, applications, and challenges. IEEE Trans Biomed Eng 60:707–714PubMedCrossRef Golberg A, Yarmush ML (2013) Nonthermal irreversible electroporation: fundamentals, applications, and challenges. IEEE Trans Biomed Eng 60:707–714PubMedCrossRef
47.
Zurück zum Zitat Ellis TL et al (2011) Nonthermal irreversible electroporation for intracranial surgical applications. Laboratory investigation. J Neurosurg 114:681–688PubMedCrossRef Ellis TL et al (2011) Nonthermal irreversible electroporation for intracranial surgical applications. Laboratory investigation. J Neurosurg 114:681–688PubMedCrossRef
48.
49.
Zurück zum Zitat Hawkins RA, O’Kane RL, Simpson IA, Vina JR (2006) Structure of the blood–brain barrier and its role in the transport of amino acids. J Nutr 136:218S–226SPubMed Hawkins RA, O’Kane RL, Simpson IA, Vina JR (2006) Structure of the blood–brain barrier and its role in the transport of amino acids. J Nutr 136:218S–226SPubMed
50.
Zurück zum Zitat Simpson IA, Carruthers A, Vannucci SJ (2007) Supply and demand in cerebral energy metabolism: the role of nutrient transporters. J Cereb Blood Flow Metab 27:1766–1791PubMedPubMedCentralCrossRef Simpson IA, Carruthers A, Vannucci SJ (2007) Supply and demand in cerebral energy metabolism: the role of nutrient transporters. J Cereb Blood Flow Metab 27:1766–1791PubMedPubMedCentralCrossRef
51.
Zurück zum Zitat Vlieghe P, Khrestchatisky M (2013) Medicinal chemistry based approaches and nanotechnology-based systems to improve CNS drug targeting and delivery. Med Res Rev 33:457–516PubMedCrossRef Vlieghe P, Khrestchatisky M (2013) Medicinal chemistry based approaches and nanotechnology-based systems to improve CNS drug targeting and delivery. Med Res Rev 33:457–516PubMedCrossRef
52.
Zurück zum Zitat Deane R, Zlokovic BV (2007) Role of the blood–brain barrier in the pathogenesis of Alzheimer’s disease. Curr Alzheimer Res 4:191–197PubMedCrossRef Deane R, Zlokovic BV (2007) Role of the blood–brain barrier in the pathogenesis of Alzheimer’s disease. Curr Alzheimer Res 4:191–197PubMedCrossRef
53.
Zurück zum Zitat Li YM, Vallera DA, Hall WA (2013) Diphtheria toxin-based targeted toxin therapy for brain tumors. J Neurooncol 114:155–164PubMedCrossRef Li YM, Vallera DA, Hall WA (2013) Diphtheria toxin-based targeted toxin therapy for brain tumors. J Neurooncol 114:155–164PubMedCrossRef
54.
Zurück zum Zitat Kannan R et al (1990) Evidence for carrier-mediated transport of glutathione across the blood–brain barrier in the rat. J Clin Invest 85:2009–2013PubMedPubMedCentralCrossRef Kannan R et al (1990) Evidence for carrier-mediated transport of glutathione across the blood–brain barrier in the rat. J Clin Invest 85:2009–2013PubMedPubMedCentralCrossRef
55.
Zurück zum Zitat Dufes C, Al Robaian M, Somani S (2013) Transferrin and the transferrin receptor for the targeted delivery of therapeutic agents to the brain and cancer cells. Ther Deliv 4:629–640PubMedCrossRef Dufes C, Al Robaian M, Somani S (2013) Transferrin and the transferrin receptor for the targeted delivery of therapeutic agents to the brain and cancer cells. Ther Deliv 4:629–640PubMedCrossRef
56.
Zurück zum Zitat Saldana SM et al (2013) Inhibition of type I insulin-like growth factor receptor signaling attenuates the development of breast cancer brain metastasis. PLoS One 8:e73406PubMedPubMedCentralCrossRef Saldana SM et al (2013) Inhibition of type I insulin-like growth factor receptor signaling attenuates the development of breast cancer brain metastasis. PLoS One 8:e73406PubMedPubMedCentralCrossRef
57.
Zurück zum Zitat Gaillard PJ, Visser CC, de Boer AG (2005) Targeted delivery across the blood–brain barrier. Expert Opin Drug Deliv 2:299–309PubMedCrossRef Gaillard PJ, Visser CC, de Boer AG (2005) Targeted delivery across the blood–brain barrier. Expert Opin Drug Deliv 2:299–309PubMedCrossRef
60.
Zurück zum Zitat Tang J et al (2014) The association between blood–cerebrospinal fluid barrier dysfunction and the therapeutic effect in tuberculous meningitis patients. Eur Neurol 71:331–336PubMedCrossRef Tang J et al (2014) The association between blood–cerebrospinal fluid barrier dysfunction and the therapeutic effect in tuberculous meningitis patients. Eur Neurol 71:331–336PubMedCrossRef
61.
Zurück zum Zitat Engelhardt B, Sorokin L (2009) The blood–brain and the blood–cerebrospinal fluid barriers: function and dysfunction. Semin Immunopathol 31:497–511PubMedCrossRef Engelhardt B, Sorokin L (2009) The blood–brain and the blood–cerebrospinal fluid barriers: function and dysfunction. Semin Immunopathol 31:497–511PubMedCrossRef
62.
Zurück zum Zitat Ek CJ, Habgood MD, Dziegielewska KM, Saunders NR (2003) Structural characteristics and barrier properties of the choroid plexuses in developing brain of the opossum (Monodelphis domestica). J Comp Neurol 460:451–464PubMedCrossRef Ek CJ, Habgood MD, Dziegielewska KM, Saunders NR (2003) Structural characteristics and barrier properties of the choroid plexuses in developing brain of the opossum (Monodelphis domestica). J Comp Neurol 460:451–464PubMedCrossRef
63.
Zurück zum Zitat Yasuda K et al (2013) Drug transporters on arachnoid barrier cells contribute to the blood–cerebrospinal fluid barrier. Drug Metab Dispos 41:923–931PubMedPubMedCentralCrossRef Yasuda K et al (2013) Drug transporters on arachnoid barrier cells contribute to the blood–cerebrospinal fluid barrier. Drug Metab Dispos 41:923–931PubMedPubMedCentralCrossRef
64.
65.
Zurück zum Zitat Tachikawa M et al (2012) A clearance system for prostaglandin D2, a sleep-promoting factor, in cerebrospinal fluid: role of the blood–cerebrospinal barrier transporters. J Pharmacol Exp Ther 343:608–616PubMedCrossRef Tachikawa M et al (2012) A clearance system for prostaglandin D2, a sleep-promoting factor, in cerebrospinal fluid: role of the blood–cerebrospinal barrier transporters. J Pharmacol Exp Ther 343:608–616PubMedCrossRef
66.
Zurück zum Zitat Saunders NR, Daneman R, Dziegielewska KM, Liddelow SA (2013) Transporters of the blood–brain and blood–CSF interfaces in development and in the adult. Mol Asp Med 34:742–752CrossRef Saunders NR, Daneman R, Dziegielewska KM, Liddelow SA (2013) Transporters of the blood–brain and blood–CSF interfaces in development and in the adult. Mol Asp Med 34:742–752CrossRef
67.
Zurück zum Zitat Nagaraja TN et al (2005) In normal rat, intraventricularly administered insulin-like growth factor-1 is rapidly cleared from CSF with limited distribution into brain. Cerebrospinal Fluid Res 2:5PubMedPubMedCentralCrossRef Nagaraja TN et al (2005) In normal rat, intraventricularly administered insulin-like growth factor-1 is rapidly cleared from CSF with limited distribution into brain. Cerebrospinal Fluid Res 2:5PubMedPubMedCentralCrossRef
68.
Zurück zum Zitat Pavan B, Paganetto G, Rossi D, Dalpiaz A (2014) Multidrug resistance in cancer or inefficacy of neuroactive agents: innovative strategies to inhibit or circumvent the active efflux transporters selectively. Drug Discov Today 19:1563–1571PubMedCrossRef Pavan B, Paganetto G, Rossi D, Dalpiaz A (2014) Multidrug resistance in cancer or inefficacy of neuroactive agents: innovative strategies to inhibit or circumvent the active efflux transporters selectively. Drug Discov Today 19:1563–1571PubMedCrossRef
69.
Zurück zum Zitat De Vries NA et al (2007) P-glycoprotein and breast cancer resistance protein: two dominant transporters working together in limiting the brain penetration of topotecan. Clin Cancer Res 13:6440–6449PubMedCrossRef De Vries NA et al (2007) P-glycoprotein and breast cancer resistance protein: two dominant transporters working together in limiting the brain penetration of topotecan. Clin Cancer Res 13:6440–6449PubMedCrossRef
70.
Zurück zum Zitat Schinkel AH et al (1994) Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood–brain barrier and to increased sensitivity to drugs. Cell 77:491–502PubMedCrossRef Schinkel AH et al (1994) Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood–brain barrier and to increased sensitivity to drugs. Cell 77:491–502PubMedCrossRef
71.
Zurück zum Zitat Demeule M et al (2002) Drug transport to the brain: key roles for the efflux pump P-glycoprotein in the blood–brain barrier. Vascul Pharmacol 38:339–348PubMedCrossRef Demeule M et al (2002) Drug transport to the brain: key roles for the efflux pump P-glycoprotein in the blood–brain barrier. Vascul Pharmacol 38:339–348PubMedCrossRef
72.
Zurück zum Zitat Gazzin S et al (2008) Differential expression of the multidrug resistance-related proteins ABCb1 and ABCc1 between blood–brain interfaces. J Comp Neurol 510:497–507PubMedCrossRef Gazzin S et al (2008) Differential expression of the multidrug resistance-related proteins ABCb1 and ABCc1 between blood–brain interfaces. J Comp Neurol 510:497–507PubMedCrossRef
73.
Zurück zum Zitat Tachikawa M et al (2005) Distinct spatio-temporal expression of ABCA and ABCG transporters in the developing and adult mouse brain. J Neurochem 95:294–304PubMedCrossRef Tachikawa M et al (2005) Distinct spatio-temporal expression of ABCA and ABCG transporters in the developing and adult mouse brain. J Neurochem 95:294–304PubMedCrossRef
74.
Zurück zum Zitat Liu X, Cheong J, Ding X, Deshmukh G (2014) Use of cassette dosing approach to examine the effects of P-glycoprotein on the brain and cerebrospinal fluid concentrations in wild-type and P-glycoprotein knockout rats. Drug Metab Dispos 42:482–491PubMedCrossRef Liu X, Cheong J, Ding X, Deshmukh G (2014) Use of cassette dosing approach to examine the effects of P-glycoprotein on the brain and cerebrospinal fluid concentrations in wild-type and P-glycoprotein knockout rats. Drug Metab Dispos 42:482–491PubMedCrossRef
75.
76.
Zurück zum Zitat Kemper EM et al (2003) Increased penetration of paclitaxel into the brain by inhibition of P-glycoprotein. Clin Cancer Res 9:2849–2855PubMed Kemper EM et al (2003) Increased penetration of paclitaxel into the brain by inhibition of P-glycoprotein. Clin Cancer Res 9:2849–2855PubMed
77.
Zurück zum Zitat Breedveld P, Beijnen JH, Schellens JH (2006) Use of P-glycoprotein and BCRP inhibitors to improve oral bioavailability and CNS penetration of anticancer drugs. Trends Pharmacol Sci 27:17–24PubMedCrossRef Breedveld P, Beijnen JH, Schellens JH (2006) Use of P-glycoprotein and BCRP inhibitors to improve oral bioavailability and CNS penetration of anticancer drugs. Trends Pharmacol Sci 27:17–24PubMedCrossRef
78.
Zurück zum Zitat Lin F et al (2013) Abcc4 together with abcb1 and abcg2 form a robust cooperative drug efflux system that restricts the brain entry of camptothecin analogues. Clin Cancer Res 19:2084–2095PubMedCrossRef Lin F et al (2013) Abcc4 together with abcb1 and abcg2 form a robust cooperative drug efflux system that restricts the brain entry of camptothecin analogues. Clin Cancer Res 19:2084–2095PubMedCrossRef
79.
Zurück zum Zitat Böck JC, Kaufmann F, Felix R (1996) Comparison of gadolinium-DTPA and macromolecular gadolinium-DTPA-polylysine for contrast-enhanced pulmonary time-of-flight magnetic resonance angiography. Invest Radiol 31:652–657PubMedCrossRef Böck JC, Kaufmann F, Felix R (1996) Comparison of gadolinium-DTPA and macromolecular gadolinium-DTPA-polylysine for contrast-enhanced pulmonary time-of-flight magnetic resonance angiography. Invest Radiol 31:652–657PubMedCrossRef
80.
Zurück zum Zitat Kornguth S et al (1990) Glioblastoma multiforme: MR imaging at 1.5 and 9.4 T after injection of polylysine-DTPA-Gd in rats. Am J Neuroradiol (AJNR) 11:313–318 Kornguth S et al (1990) Glioblastoma multiforme: MR imaging at 1.5 and 9.4 T after injection of polylysine-DTPA-Gd in rats. Am J Neuroradiol (AJNR) 11:313–318
81.
Zurück zum Zitat Zagzag D, Goldenberg M, Brem S (1989) Angiogenesis and blood–brain barrier breakdown modulate CT contrast enhancement: an experimental study in a rabbit brain–tumor model. Am J Roentgenol (AJR) 153:141–146CrossRef Zagzag D, Goldenberg M, Brem S (1989) Angiogenesis and blood–brain barrier breakdown modulate CT contrast enhancement: an experimental study in a rabbit brain–tumor model. Am J Roentgenol (AJR) 153:141–146CrossRef
82.
Zurück zum Zitat Awasthi R et al (2012) Discriminant analysis to classify glioma grading using dynamic contrast-enhanced MRI and immunohistochemical markers. Neuroradiology 54:205–213PubMedCrossRef Awasthi R et al (2012) Discriminant analysis to classify glioma grading using dynamic contrast-enhanced MRI and immunohistochemical markers. Neuroradiology 54:205–213PubMedCrossRef
83.
Zurück zum Zitat Yonemori K et al (2010) Disruption of the blood brain barrier by brain metastases of triple-negative and basal-type breast cancer but not HER2/neu-positive breast cancer. Cancer 116:302–308PubMedCrossRef Yonemori K et al (2010) Disruption of the blood brain barrier by brain metastases of triple-negative and basal-type breast cancer but not HER2/neu-positive breast cancer. Cancer 116:302–308PubMedCrossRef
84.
Zurück zum Zitat Spuch C, Ortolano S, Navarro C (2012) LRP-1 and LRP-2 receptors function in the membrane neuron. Trafficking mechanisms and proteolytic processing in Alzheimer’s disease. Front Physiol 3:269PubMedPubMedCentralCrossRef Spuch C, Ortolano S, Navarro C (2012) LRP-1 and LRP-2 receptors function in the membrane neuron. Trafficking mechanisms and proteolytic processing in Alzheimer’s disease. Front Physiol 3:269PubMedPubMedCentralCrossRef
85.
Zurück zum Zitat Demeule M et al (2008) Involvement of the low-density lipoprotein receptor-related protein in the transcytosis of the brain delivery vector angiopep-2. J Neurochem 106:1534–1544PubMedCrossRef Demeule M et al (2008) Involvement of the low-density lipoprotein receptor-related protein in the transcytosis of the brain delivery vector angiopep-2. J Neurochem 106:1534–1544PubMedCrossRef
86.
Zurück zum Zitat Thomas FC et al (2009) Uptake of ANG1005, a novel paclitaxel derivative, through the blood–brain barrier into brain and experimental brain metastases of breast cancer. Pharm Res 26:2486–2494PubMedPubMedCentralCrossRef Thomas FC et al (2009) Uptake of ANG1005, a novel paclitaxel derivative, through the blood–brain barrier into brain and experimental brain metastases of breast cancer. Pharm Res 26:2486–2494PubMedPubMedCentralCrossRef
87.
Zurück zum Zitat Drappatz J et al (2013) Phase I study of GRN1005 in recurrent malignant glioma. Clin Cancer Res 19:1567–1576PubMedCrossRef Drappatz J et al (2013) Phase I study of GRN1005 in recurrent malignant glioma. Clin Cancer Res 19:1567–1576PubMedCrossRef
88.
Zurück zum Zitat Kurzrock R et al (2012) 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 11:308–316PubMedCrossRef Kurzrock R et al (2012) 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 11:308–316PubMedCrossRef
89.
Zurück zum Zitat Lin NU, Schwartzberg LS, Kesari S, Yardley DA, Verma S, Anders CK, Shih T, Shen Y, Miller K (2012) A phase 2, multi-center, open label study evaluating the efficacy and safety of GRN1005 alone or in combination with trastuzumab in patients with brain metastases from breast cancer. Cancer Res 72:1057–1065CrossRef Lin NU, Schwartzberg LS, Kesari S, Yardley DA, Verma S, Anders CK, Shih T, Shen Y, Miller K (2012) A phase 2, multi-center, open label study evaluating the efficacy and safety of GRN1005 alone or in combination with trastuzumab in patients with brain metastases from breast cancer. Cancer Res 72:1057–1065CrossRef
91.
Zurück zum Zitat Etheridge ML et al (2013) The big picture on nanomedicine: the state of investigational and approved nanomedicine products. Nanomedicine 9:1–14PubMedPubMedCentralCrossRef Etheridge ML et al (2013) The big picture on nanomedicine: the state of investigational and approved nanomedicine products. Nanomedicine 9:1–14PubMedPubMedCentralCrossRef
92.
Zurück zum Zitat Metselaar JM, Storm G (2005) Liposomes in the treatment of inflammatory disorders. Expert Opin Drug Deliv 2:465–476PubMedCrossRef Metselaar JM, Storm G (2005) Liposomes in the treatment of inflammatory disorders. Expert Opin Drug Deliv 2:465–476PubMedCrossRef
93.
Zurück zum Zitat Fukumura D, Duda DG, Munn LL, Jain RK (2010) Tumor microvasculature and microenvironment: novel insights through intravital imaging in pre-clinical models. Microcirculation 17:206–225PubMedPubMedCentralCrossRef Fukumura D, Duda DG, Munn LL, Jain RK (2010) Tumor microvasculature and microenvironment: novel insights through intravital imaging in pre-clinical models. Microcirculation 17:206–225PubMedPubMedCentralCrossRef
94.
Zurück zum Zitat Groll AH et al (2000) Comparative efficacy and distribution of lipid formulations of amphotericin B in experimental Candida albicans infection of the central nervous system. J Infect Dis 182:274–282PubMedCrossRef Groll AH et al (2000) Comparative efficacy and distribution of lipid formulations of amphotericin B in experimental Candida albicans infection of the central nervous system. J Infect Dis 182:274–282PubMedCrossRef
96.
Zurück zum Zitat Birngruber T et al (2013) Cerebral open flow microperfusion: a new in vivo technique for continuous measurement of substance transport across the intact blood–brain barrier. Clin Exp Pharmacol Physiol 40:864–871PubMedCrossRef Birngruber T et al (2013) Cerebral open flow microperfusion: a new in vivo technique for continuous measurement of substance transport across the intact blood–brain barrier. Clin Exp Pharmacol Physiol 40:864–871PubMedCrossRef
97.
Zurück zum Zitat Gaillard PJ et al (2014) Pharmacokinetics, brain delivery, and efficacy in brain tumor-bearing mice of glutathione pegylated liposomal doxorubicin (2B3-101). PLoS One 9:e82331PubMedPubMedCentralCrossRef Gaillard PJ et al (2014) Pharmacokinetics, brain delivery, and efficacy in brain tumor-bearing mice of glutathione pegylated liposomal doxorubicin (2B3-101). PLoS One 9:e82331PubMedPubMedCentralCrossRef
98.
Zurück zum Zitat Milojkovic Kerklaan B et al (2013) Phase I dose escalating study of 2B3-101, glutathione pegylated liposomal doxorubicin, in patients with solid tumors and brain metastases or reccurent malignant glioma. Neuro-oncol 15, abstract 15 Milojkovic Kerklaan B et al (2013) Phase I dose escalating study of 2B3-101, glutathione pegylated liposomal doxorubicin, in patients with solid tumors and brain metastases or reccurent malignant glioma. Neuro-oncol 15, abstract 15
99.
Zurück zum Zitat Li Y et al (2012) A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas. Biomaterials 33:3899–3908PubMedCrossRef Li Y et al (2012) A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas. Biomaterials 33:3899–3908PubMedCrossRef
100.
Zurück zum Zitat Grover A, Hirani A, Pathak Y, Sutariya V (2014) Brain-targeted delivery of docetaxel by glutathione-coated nanoparticles for brain cancer. AAPS PharmSciTech 15:1562–1568PubMedPubMedCentralCrossRef Grover A, Hirani A, Pathak Y, Sutariya V (2014) Brain-targeted delivery of docetaxel by glutathione-coated nanoparticles for brain cancer. AAPS PharmSciTech 15:1562–1568PubMedPubMedCentralCrossRef
101.
Zurück zum Zitat Geldenhuys W, Mbimba T, Bui T, Harrison K, Sutariya V (2011) Brain-targeted delivery of paclitaxel using glutathione-coated nanoparticles for brain cancers. J Drug Target 19:837–845PubMedCrossRef Geldenhuys W, Mbimba T, Bui T, Harrison K, Sutariya V (2011) Brain-targeted delivery of paclitaxel using glutathione-coated nanoparticles for brain cancers. J Drug Target 19:837–845PubMedCrossRef
103.
Zurück zum Zitat Kanasty R, Dorkin JR, Vegas A, Anderson D (2013) Delivery materials for siRNA therapeutics. Nat Mater 12:967–977PubMedCrossRef Kanasty R, Dorkin JR, Vegas A, Anderson D (2013) Delivery materials for siRNA therapeutics. Nat Mater 12:967–977PubMedCrossRef
105.
Zurück zum Zitat Hegi ME et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003PubMedCrossRef Hegi ME et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003PubMedCrossRef
106.
Zurück zum Zitat Tsujiuchi T et al (2014) Preclinical evaluation of an O(6)-methylguanine-DNA methyltransferase-siRNA/liposome complex administered by convection-enhanced delivery to rat and porcine brains. Am J Transl Res 6:169–178PubMedPubMedCentral Tsujiuchi T et al (2014) Preclinical evaluation of an O(6)-methylguanine-DNA methyltransferase-siRNA/liposome complex administered by convection-enhanced delivery to rat and porcine brains. Am J Transl Res 6:169–178PubMedPubMedCentral
108.
Zurück zum Zitat Yang ZZ, Li JQ, Wang ZZ, Dong DW, Qi XR (2014) Tumor-targeting dual peptides-modified cationic liposomes for delivery of siRNA and docetaxel to gliomas. Biomaterials 35:5226–5239PubMedCrossRef Yang ZZ, Li JQ, Wang ZZ, Dong DW, Qi XR (2014) Tumor-targeting dual peptides-modified cationic liposomes for delivery of siRNA and docetaxel to gliomas. Biomaterials 35:5226–5239PubMedCrossRef
109.
Zurück zum Zitat Patil A, Sherbet G (2015) Therapeutic approach to the management of HER2-positive breast cancer metastatic to the brain. Cancer Lett 35:93–99CrossRef Patil A, Sherbet G (2015) Therapeutic approach to the management of HER2-positive breast cancer metastatic to the brain. Cancer Lett 35:93–99CrossRef
110.
Zurück zum Zitat Patil R, Ljubimov AV, Gangalum PR, Ding H, Portilla-Arias J, Wagner S, Inoue S, Konda B, Rekechenetskiy A, Chesnokova A, Markman JL, Ljubimov VA, Li D, Prasad RS, Black KL, Holler E, Ljubimova J (2015) MRI virtual biopsy and treatment of brain metastatic tumors with targeted nanobioconjugates: nanoclinic in the brain. ACS Nano 9(5):5594–608. doi:10.1021/acsnano.5b01872 PubMedPubMedCentralCrossRef Patil R, Ljubimov AV, Gangalum PR, Ding H, Portilla-Arias J, Wagner S, Inoue S, Konda B, Rekechenetskiy A, Chesnokova A, Markman JL, Ljubimov VA, Li D, Prasad RS, Black KL, Holler E, Ljubimova J (2015) MRI virtual biopsy and treatment of brain metastatic tumors with targeted nanobioconjugates: nanoclinic in the brain. ACS Nano 9(5):5594–608. doi:10.​1021/​acsnano.​5b01872 PubMedPubMedCentralCrossRef
111.
Zurück zum Zitat Regina A, Demeule M, Tripathy S, Lord-Dufour S, Currie JC, Iddir M, Annabi B, Castaigne JP, Lachowicz J (2015) ANG4043, a novel brain-penetrant peptide-mAb conjugate, is efficacious against HER2-positive intracranial tumors in mice. Mol Cancer Ther 14(1):129–140. doi:10.1158/1535-7163.MCT-14-0399 PubMedCrossRef Regina A, Demeule M, Tripathy S, Lord-Dufour S, Currie JC, Iddir M, Annabi B, Castaigne JP, Lachowicz J (2015) ANG4043, a novel brain-penetrant peptide-mAb conjugate, is efficacious against HER2-positive intracranial tumors in mice. Mol Cancer Ther 14(1):129–140. doi:10.​1158/​1535-7163.​MCT-14-0399 PubMedCrossRef
112.
Zurück zum Zitat Van den Bent MJ et al (2013) Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol 31:344–350PubMedCrossRef Van den Bent MJ et al (2013) Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol 31:344–350PubMedCrossRef
113.
Zurück zum Zitat Cairncross G et al (2013) Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol 31:337–343PubMedPubMedCentralCrossRef Cairncross G et al (2013) Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol 31:337–343PubMedPubMedCentralCrossRef
114.
115.
Zurück zum Zitat Shaw EG et al (2012) Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. J Clin Oncol 30:3065–3070PubMedPubMedCentralCrossRef Shaw EG et al (2012) Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. J Clin Oncol 30:3065–3070PubMedPubMedCentralCrossRef
116.
Zurück zum Zitat Buckner JC, Pugh SL, Shaw EG, Gilbert MR, Barger G, Coons S, Ricci P, Bullard D, Brown PD, Stelzer K, Brachman D, Suh JH, Schultz CJ, Bahary J-P, Jean Fisher B, Haro WJC, Mehta MP (2014) Phase III study of radiation therapy (RT) with or without procarbazine, CCNU, and vincristine (PCV) in low-grade glioma: RTOG 9802 with alliance, ECOG, and SWOG. J Clin Oncol ASCO Annu Meet Abstr 32, abstract 2000 Buckner JC, Pugh SL, Shaw EG, Gilbert MR, Barger G, Coons S, Ricci P, Bullard D, Brown PD, Stelzer K, Brachman D, Suh JH, Schultz CJ, Bahary J-P, Jean Fisher B, Haro WJC, Mehta MP (2014) Phase III study of radiation therapy (RT) with or without procarbazine, CCNU, and vincristine (PCV) in low-grade glioma: RTOG 9802 with alliance, ECOG, and SWOG. J Clin Oncol ASCO Annu Meet Abstr 32, abstract 2000
117.
Zurück zum Zitat Otieno MA, Baggs RB, Hayes JD, Anders MW (1997) Immunolocalization of microsomal glutathione S-transferase in rat tissues. Drug Metab Dispos 25:12–20PubMed Otieno MA, Baggs RB, Hayes JD, Anders MW (1997) Immunolocalization of microsomal glutathione S-transferase in rat tissues. Drug Metab Dispos 25:12–20PubMed
118.
Zurück zum Zitat Takeda A, Takatsuka K, Connor JR, Oku N (2001) Abnormal iron accumulation in the brain of neonatal hypotransferrinemic mice. Brain Res 7:154–161CrossRef Takeda A, Takatsuka K, Connor JR, Oku N (2001) Abnormal iron accumulation in the brain of neonatal hypotransferrinemic mice. Brain Res 7:154–161CrossRef
119.
Zurück zum Zitat Roberts LM et al (2008) Subcellular localization of transporters along the rat blood–brain barrier and blood–cerebral–spinal fluid barrier by in vivo biotinylation. Neuroscience 155:423–438PubMedCrossRef Roberts LM et al (2008) Subcellular localization of transporters along the rat blood–brain barrier and blood–cerebral–spinal fluid barrier by in vivo biotinylation. Neuroscience 155:423–438PubMedCrossRef
120.
Zurück zum Zitat Redzic Z (2011) Molecular biology of the blood–brain and the blood–cerebrospinal fluid barriers: similarities and differences. Fluids Barriers CNS 8:3PubMedPubMedCentralCrossRef Redzic Z (2011) Molecular biology of the blood–brain and the blood–cerebrospinal fluid barriers: similarities and differences. Fluids Barriers CNS 8:3PubMedPubMedCentralCrossRef
121.
Zurück zum Zitat Brandsma D et al (2014) Phase 1/2a study of glutathione PEGylated liposomal doxorubicin (2B3-101) in patients with brain metastases (BM) from solid tumors or recurrent high grade glioma. Ann Oncol 25(suppl):iv146–iv164 Brandsma D et al (2014) Phase 1/2a study of glutathione PEGylated liposomal doxorubicin (2B3-101) in patients with brain metastases (BM) from solid tumors or recurrent high grade glioma. Ann Oncol 25(suppl):iv146–iv164
122.
Zurück zum Zitat Regina A et al (2008) Antitumour activity of ANG1005, a conjugate between paclitaxel and the new brain delivery vector Angiopep-2. Br J Pharmacol 155:185–197PubMedPubMedCentralCrossRef Regina A et al (2008) Antitumour activity of ANG1005, a conjugate between paclitaxel and the new brain delivery vector Angiopep-2. Br J Pharmacol 155:185–197PubMedPubMedCentralCrossRef
123.
Zurück zum Zitat Pang Z et al (2011) Enhanced intracellular delivery and chemotherapy for glioma rats by transferrin-conjugated biodegradable polymersomes loaded with doxorubicin. Bioconjug Chem 22:1171–1180PubMedCrossRef Pang Z et al (2011) Enhanced intracellular delivery and chemotherapy for glioma rats by transferrin-conjugated biodegradable polymersomes loaded with doxorubicin. Bioconjug Chem 22:1171–1180PubMedCrossRef
125.
Zurück zum Zitat Sarkar G, Curran GL, Sarkaria JN, Lowe VJ, Jenkins RB (2014) Peptide carrier-mediated non-covalent delivery of unmodified cisplatin, methotrexate and other agents via intravenous route to the brain. PLoS One 9:e97655PubMedPubMedCentralCrossRef Sarkar G, Curran GL, Sarkaria JN, Lowe VJ, Jenkins RB (2014) Peptide carrier-mediated non-covalent delivery of unmodified cisplatin, methotrexate and other agents via intravenous route to the brain. PLoS One 9:e97655PubMedPubMedCentralCrossRef
126.
Zurück zum Zitat Yang Y et al (2014) PEGylated liposomes with NGR ligand and heat-activable cell-penetrating peptide-doxorubicin conjugate for tumor-specific therapy. Biomaterials 35:4368–4381PubMedCrossRef Yang Y et al (2014) PEGylated liposomes with NGR ligand and heat-activable cell-penetrating peptide-doxorubicin conjugate for tumor-specific therapy. Biomaterials 35:4368–4381PubMedCrossRef
127.
Zurück zum Zitat Dilnawaz F et al (2012) The transport of non-surfactant based paclitaxel loaded magnetic nanoparticles across the blood brain barrier in a rat model. Biomaterials 33:2936–2951PubMedCrossRef Dilnawaz F et al (2012) The transport of non-surfactant based paclitaxel loaded magnetic nanoparticles across the blood brain barrier in a rat model. Biomaterials 33:2936–2951PubMedCrossRef
128.
Zurück zum Zitat Wang P, Liu Y, Shang X, Xue Y (2011) CRM197-induced blood–brain barrier permeability increase is mediated by upregulation of caveolin-1 protein. J Mol Neurosci 43:485–492PubMedCrossRef Wang P, Liu Y, Shang X, Xue Y (2011) CRM197-induced blood–brain barrier permeability increase is mediated by upregulation of caveolin-1 protein. J Mol Neurosci 43:485–492PubMedCrossRef
129.
Zurück zum Zitat Gooding M, Malhotra M, McCarthy DJ, Godinho BM, Cryan JF, Darcy R, O’Driscoll C (2015) Synthesis and characterization of rabies virus glycoprotein-tagged amphiphilic cyclodextrins for siRNA delivery in human glioblastoma cells: in vitro analysis. Eur J Pharm Sci 71:80–92. doi:10.1016/j.ejps.2015.02.007 PubMedCrossRef Gooding M, Malhotra M, McCarthy DJ, Godinho BM, Cryan JF, Darcy R, O’Driscoll C (2015) Synthesis and characterization of rabies virus glycoprotein-tagged amphiphilic cyclodextrins for siRNA delivery in human glioblastoma cells: in vitro analysis. Eur J Pharm Sci 71:80–92. doi:10.​1016/​j.​ejps.​2015.​02.​007 PubMedCrossRef
130.
Zurück zum Zitat Kievit FM, Stephen ZR, Wang K, Dayringer CJ, Sham JG, Ellenbogen RG, Silber JR, Zhang M (2015) Nanoparticle mediated silencing of DNA repair sensitizes pediatric brain tumor cells to γ-irradiation. Mol Oncol 29:1071–1080CrossRef Kievit FM, Stephen ZR, Wang K, Dayringer CJ, Sham JG, Ellenbogen RG, Silber JR, Zhang M (2015) Nanoparticle mediated silencing of DNA repair sensitizes pediatric brain tumor cells to γ-irradiation. Mol Oncol 29:1071–1080CrossRef
Metadaten
Titel
Strategies to target drugs to gliomas and CNS metastases of solid tumors
verfasst von
B. Milojkovic Kerklaan
O. van Tellingen
A. D. R. Huitema
J. H. Beijnen
W. Boogerd
J. H. M. Schellens
D. Brandsma
Publikationsdatum
01.03.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Neurology / Ausgabe 3/2016
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-015-7919-9

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