Advertisement

Brain Cancer Receptors and Targeting Strategies

  • Rijo John
  • Heero Vaswani
  • Prajakta Dandekar
  • Padma V. DevarajanEmail author
Chapter
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 39)

Abstract

Brain cancer is regarded as the most widespread cancer of the central nervous system. The complexity of the glial cell tumor renders the survival and prognosis of glioma difficult, even after conventional chemotherapy, radiotherapy, and surgery treatments. The major concern is the formidable blood–brain barrier (BBB) that guards the entry of all exogenous moieties into the brain. This chapter addresses in brief the various approaches to bypass the BBB. Among different strategies, receptor-oriented drug delivery takes advantage of receptors on the BBB to traverse into the brain and if appropriately designed can enter the cancer cells through receptors overexpressed on their surface. This chapter will also summarize the various receptors, their physiology, ligands for the receptor, and drug-delivery strategies that could improve brain cancer therapy.

Keywords

Brain cancer Receptor-mediated endocytosis Low-density lipoprotein Integrin Interleukin Lactoferrin 

Abbreviations

ADC

Antibody–drug conjugate

ADMIDAS

Adjacent to MIDAS

AP1

CRKRLDRNC peptide

Apo B

Apolipoprotein B

Apo E

Apolipoprotein E

AQP4

Aquaporin-4

BBB

Blood-brain barrier

BSA

Bovine serum albumin

CNS

Central nervous system

DHA

Docosahexaenoic acid

DNA

Deoxyribonucleic acid

DOX

Doxorubicin

EGF

Epidermal growth factor

EGFR

Epithelial growth factor receptor

EPR

Enhanced permeability and retention

GBM

Glioblastoma

IC50

Half-maximal inhibitory concentration

IL

Interleukin

IL-13Rα2

Interleukin-13 receptor subunit alpha-2

IL-2Rγc

Interleukin-2 receptor common gamma chain

Kd

Dissociation constant

LDH

Lactate dehydrogenase

LDL

Low-density lipoprotein

LDLR

Low-density lipoprotein receptor

Lf

Lactoferrin

LfR

Lactoferrin receptor

LRP

Low-density lipoprotein receptor-related protein

MIDAS

Metal ion-dependent adhesion Site

mPEG

Methoxy polyethylene glycol

MTT

(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide

NPs

Nanoparticles

PE

Paired end

PEG

Polyethylene glycol

PI3 kinase

Phosphoinositide-3-kinase

PLA

Poly lactic acid

PTX

Paclitaxel

RAP

Receptor-associated protein

RGD

Arginine–glycine–aspartic acid

RNA

Ribonucleic acid

STAT 6

Signal transducer and activator of transcription 6

Tf

Transferrin

TPGS

D-ɑ-tocopheryl polyethylene glycol succinate

VLDLR

Very low-density lipoprotein receptor

References

  1. 1.
    Wrensch M, Minn Y, Chew T, Bondy M, Berger MS. Epidemiology of primary brain tumors: Current concepts and review of the literature. Neuro Oncol. 2002;4(4):278–99.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Deeken JF, Loscher W. The blood-brain barrier and cancer: transporters, treatment, and Trojan horses. Clin Cancer Res. 2007;13(6):1663–74.PubMedCrossRefGoogle Scholar
  3. 3.
    Pardridge WM. Drug transport across the blood–brain barrier. J Cereb Blood Flow Metab. 2012;32(11):1959–72.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Dong X. Current strategies for brain drug delivery. Theranostics. 2018;8(6):1481–93.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Lalatsa A, Butt AM. Physiology of the blood–brain barrier and mechanisms of transport across the BBB. In: Nanotechnology-based targeted drug delivery systems for brain tumors. Academic Press, USA. 2018;49–74.CrossRefGoogle Scholar
  6. 6.
    Simard M, Nedergaard M. The neurobiology of glia in the context of water and ion homeostasis. Neuroscience. 2004;129(4):877–96.PubMedCrossRefGoogle Scholar
  7. 7.
    Wong AD, Ye M, Levy AF, Rothstein JD, Bergles DE, Searson PC. The blood-brain barrier: an engineering perspective. Front Neuroeng. 2013;6:7.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Laksitorini M, Prasasty VD, Kiptoo PK, Siahaan TJ. Pathways and progress in improving drug delivery through the intestinal mucosa and blood–brain barriers. Ther Deliv. 2014;5(10):1143–63.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Salamat-Miller N, Johnston TP. Current strategies used to enhance the paracellular transport of therapeutic polypeptides across the intestinal epithelium. Int J Pharm. 2005;294(1–2):201–16.PubMedCrossRefGoogle Scholar
  10. 10.
    Shinde RL, Jindal AB, Devarajan PV. Microemulsions and nanoemulsions for targeted drug delivery to the brain. Curr Nanosci. 2011;7(1):119–33.CrossRefGoogle Scholar
  11. 11.
    Karanth H, Murthy RS. Nanotechnology in brain targeting. Int. J. Pharm. Sci. Nanotechnol. 2008;1:10–24.Google Scholar
  12. 12.
    Bellettato CM, Scarpa M. Possible strategies to cross the blood–brain barrier. Ital J Pediatr. 2018;44(2):131.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Liu F, Li X, Zhang L-Y, Song Q-R, Zhang M, Zhao C-X, et al. Stimuli-responsive Nanocarriers for drug delivery to the central nervous system. CNANO. 2015;12(1):4–17.CrossRefGoogle Scholar
  14. 14.
    Hervé F, Ghinea N, Scherrmann J-M. CNS delivery via adsorptive transcytosis. AAPS J. 2008;10(3):455–72.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Xiao G, Gan L-S. Receptor-mediated endocytosis and brain delivery of therapeutic biologics. Int J Cell Biol. 2013;2013:1–14.CrossRefGoogle Scholar
  16. 16.
    Gabathuler R. Approaches to transport therapeutic drugs across the blood–brain barrier to treat brain diseases. Neurobiol Dis. 2010;37(1):48–57.PubMedCrossRefGoogle Scholar
  17. 17.
    Golden PL, Maccagnan TJ, Pardridge WM. Human blood-brain barrier leptin receptor. Binding and endocytosis in isolated human brain microvessels. J Clin Investig. 1997;99(1):14–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Duffy KR, Pardridge WM. Blood-brain barrier transcytosis of insulin in developing rabbits. Brain Res. 1987;420(1):32–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Akhtar MJ, Ahamed M, Alhadlaq HA, Alrokayan SA, Kumar S. Targeted anticancer therapy: overexpressed receptors and nanotechnology. Clin Chim Acta. 2014;436:78–92.PubMedCrossRefGoogle Scholar
  20. 20.
    Wei X, Chen X, Ying M, Lu W. Brain tumor-targeted drug delivery strategies. Acta Pharm Sin B. 2014;4(3):193–201.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release. 2000;65(1–2):271–84.PubMedCrossRefGoogle Scholar
  22. 22.
    Maeda H. Tumor-selective delivery of macromolecular drugs via the EPR effect: background and future prospects. Bioconjug Chem. 2010;21(5):797–802.PubMedCrossRefGoogle Scholar
  23. 23.
    Wang Y-Y, Lui PC, Li JY. Receptor-mediated therapeutic transport across the blood–brain barrier. Immunotherapy. 2009;1(6):983–93.PubMedCrossRefGoogle Scholar
  24. 24.
    Lajoie JM, Shusta EV. Targeting receptor-mediated transport for delivery of biologics across the blood-brain barrier. Annu Rev Pharmacol Toxicol. 2015;55(1):613–31.PubMedCrossRefGoogle Scholar
  25. 25.
    Zhang B, Sun X, Mei H, Wang Y, Liao Z, Chen J, et al. LDLR-mediated peptide-22-conjugated nanoparticles for dual-targeting therapy of brain glioma. Biomaterials. 2013;34(36):9171–82.PubMedCrossRefGoogle Scholar
  26. 26.
    Xu J, Potenza MN, Calhoun VD. Spatial ICA reveals functional activity hidden from traditional fMRI GLM-based analyses. Front Neurosci. 2013;7:154.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Brown M, Goldstein J. A receptor-mediated pathway for cholesterol homeostasis. Science. 1986;232(4746):34–47.PubMedCrossRefGoogle Scholar
  28. 28.
    Li Y, Cam J, Bu G. Low-density lipoprotein receptor family. Mol Neurobiol. 2001;23:15.Google Scholar
  29. 29.
    Prassl R, Laggner P. Molecular structure of low density lipoprotein: current status and future challenges. Eur Biophys J. 2009;38(2):145–58.PubMedCrossRefGoogle Scholar
  30. 30.
    Nikanjam M, Blakely EA, Bjornstad KA, Shu X, Budinger TF, Forte TM. Synthetic nano-low density lipoprotein as targeted drug delivery vehicle for glioblastoma multiforme. Int J Pharm. 2007;328(1):86–94.PubMedCrossRefGoogle Scholar
  31. 31.
    Cassidy SM, Strobel FW, Wasan KM. Plasma lipoprotein distribution of liposomal nystatin is influenced by protein content of high-density lipoproteins. Antimicrob Agents Chemother. 1998;42(8):1878–88.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Lee CK, Brown C, Gralla RJ, Hirsh V, Thongprasert S, Tsai C-M, et al. Impact of EGFR inhibitor in non–small cell lung Cancer on progression-free and overall survival: a meta-analysis. JNCI J Nat Cancer Inst. 2013;105(9):595–605.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Orlova EV, Sherman MB, Chiu W, Mowri H, Smith LC, Gotto AM. Three-dimensional structure of low density lipoproteins by electron cryomicroscopy. Proc Natl Acad Sci. 1999;96(15):8420–5.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Wang Y-Y, Lui PC, Li JY. Receptor-mediated therapeutic transport across the blood–brain barrier. Immunotherapy. 2009;1(6):983–93.PubMedCrossRefGoogle Scholar
  35. 35.
    Papademetriou IT, Porter T. Promising approaches to circumvent the blood–brain barrier: progress, pitfalls and clinical prospects in brain cancer. Ther Deliv. 2015;6(8):989–1016.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Muro S. Challenges in design and characterization of ligand-targeted drug delivery systems. J Control Release. 2012;164(2):125–37.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Desgrosellier JS, Cheresh DA. Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer. 2010;10(1):9–22.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Taga T, Suzuki A, Gonzalez-Gomez I, Gilles FH, Stins M, Shimada H, et al. alpha v-Integrin antagonist EMD 121974 induces apoptosis in brain tumor cells growing on vitronectin and tenascin. Int J Cancer. 2002;98(5):690–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Beer AJ. Positron emission tomography using [18F]Galacto-RGD identifies the level of integrin v 3 expression in man. Clin Cancer Res. 2006;12(13):3942–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Barczyk M, Carracedo S, Gullberg D. Integrins. Cell Tissue Res. 2010;339(1):269–80.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Humphries M. Mapping functional residues onto integrin crystal structures. Curr Opin Struct Biol. 2003;13(2):236–43.PubMedCrossRefGoogle Scholar
  42. 42.
    Lee J-O, Bankston LA, Arnaout MA, Liddington RC. Two conformations of the integrin A-domain (I-domain): a pathway for activation? Structure. 1995;3(12):1333–40.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Clark E, Brugge J. Integrins and signal transduction pathways: the road taken. Science. 1995;268(5208):233–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Arnaout MA, Goodman SL, Xiong J-P. Coming to grips with integrin binding to ligands. Curr Opin Cell Biol. 2002;14(5):641–52.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Xiao X. Modeling gross primary production of temperate deciduous broadleaf forest using satellite images and climate data. Remote Sens Environ. 2004;91(2):256–70.CrossRefGoogle Scholar
  46. 46.
    Shin S, Wolgamott L, Yoon S-O. Integrin trafficking and tumor progression. Int J Cell Biol. 2012;2012:1–7.CrossRefGoogle Scholar
  47. 47.
    van der Flier A, Sonnenberg A. Structural and functional aspects of filamins. Biochim Biophys Acta Mol Cell Res. 2001;1538(2–3):99–117.CrossRefGoogle Scholar
  48. 48.
    Plow EF, Haas TA, Zhang L, Loftus J, Smith JW. Ligand binding to integrins. J Biol Chem. 2000;275(29):21785–8.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Humphries JD. Integrin ligands at a glance. J Cell Sci. 2006;119(19):3901–3.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Mintz A, Gibo DM, Slagle-Webb B, Christensent ND, Debinski W. IL-13Rα2 is a glioma-restricted receptor for interleukin-13. Neoplasia. 2002;4(5):388–99.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Kosmopoulos M, Christofides A, Drekolias D, Zavras PD, Gargalionis AN, Piperi C. Critical role of IL-8 targeting in gliomas. Curr Med Chem. 2018;25(17):1954–67.PubMedCrossRefGoogle Scholar
  52. 52.
    Arima K, Sato K, Tanaka G, Kanaji S, Terada T, Honjo E, et al. Characterization of the interaction between interleukin-13 and interleukin-13 receptors. J Biol Chem. 2005;280(26):24915–22.PubMedCrossRefGoogle Scholar
  53. 53.
    Joshi BH, Kawakami K, Leland P, Puri RK. Heterogeneity in interleukin-13 receptor expression and subunit structure in squamous cell carcinoma of head and neck: differential sensitivity to chimeric fusion proteins comprised of interleukin-13 and a mutated form of pseudomonas exotoxin. Clin Cancer Res. 2002;8(6):1948–56.PubMedGoogle Scholar
  54. 54.
    Legrand D, Pierce A, Elass E, Carpentier M, Mariller C, Mazurier J. Lactoferrin structure and functions. In: Bösze Z, editor. Bioactive components of milk. 2008. p. 163–94.Google Scholar
  55. 55.
    Suzuki YA, Lopez V, Lönnerdal B. Lactoferrin: mammalian lactoferrin receptors: structure and function. Cell Mol Life Sci. 2005;62(22):2560–75.PubMedCrossRefGoogle Scholar
  56. 56.
    Curran CS, Demick KP, Mansfield JM. Lactoferrin activates macrophages via TLR4-dependent and -independent signaling pathways. Cell Immunol. 2006;242(1):23–30.PubMedCrossRefGoogle Scholar
  57. 57.
    Jiang R, Lopez V, Kelleher SL, Lönnerdal B. Apo- and holo-lactoferrin are both internalized by lactoferrin receptor via clathrin-mediated endocytosis but differentially affect ERK-signaling and cell proliferation in caco-2 cells. J Cell Physiol. 2011;226(11):3022–31.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Sharma P, Debinski W. Receptor-targeted glial brain tumor therapies. Int J Mol Sci. 2018;19(11):3326.PubMedCentralCrossRefPubMedGoogle Scholar
  59. 59.
    Large DE, Soucy JR, Hebert J, Auguste DT. Advances in receptor-mediated, tumor-targeted drug delivery. Adv Ther. 2019;2(1):1800091.CrossRefGoogle Scholar
  60. 60.
    Kratz F, Müller IA, Ryppa C, Warnecke A. Prodrug strategies in anticancer chemotherapy. ChemMedChem. 2008;3(1):20–53.PubMedCrossRefGoogle Scholar
  61. 61.
    Rautio J, Laine K, Gynther M, Savolainen J. Prodrug approaches for CNS delivery. AAPS J. 2008;10(1):92–102.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Xu G, McLeod HL. Strategies for enzyme/prodrug Cancer therapy. Clin Cancer Res. 2001;7(11):3314–24.PubMedGoogle Scholar
  63. 63.
    Chari RVJ, Miller ML, Widdison WC. Antibody-drug conjugates: an emerging concept in cancer therapy. Angew Chem Int Ed. 2014;53(15):3796–827.CrossRefGoogle Scholar
  64. 64.
    Lambert JM, Morris CQ. Antibody–drug conjugates (ADCs) for personalized treatment of solid tumors: a review. Adv Ther. 2017;34(5):1015–35.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Erickson HK, Widdison WC, Mayo MF, Whiteman K, Audette C, Wilhelm SD, et al. Tumor delivery and in vivo processing of disulfide-linked and thioether-linked antibody−maytansinoid conjugates. Bioconjug Chem. 2009;21(1):84–92.CrossRefGoogle Scholar
  66. 66.
    Sharkey RM, Goldenberg DM. Use of antibodies and immunoconjugates for the therapy of more accessible cancers. Adv Drug Deliv Rev. 2008;60(12):1407–20.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Parakh S, Parslow AC, Gan HK, Scott AM. Antibody-mediated delivery of therapeutics for cancer therapy. Expert Opin Drug Deliv. 2016;13(3):401–19.PubMedCrossRefGoogle Scholar
  68. 68.
    Razpotnik R, Novak N, Čurin Šerbec V, Rajcevic U. Targeting malignant brain tumors with antibodies. Front Immunol. 2017;8:1181.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Muntoni E, Martina K, Marini E, Giorgis M, Lazzarato L, Salaroglio I, et al. Methotrexate-loaded solid lipid nanoparticles: protein functionalization to improve brain biodistribution. Pharmaceutics. 2019;11(2):65.PubMedCentralCrossRefPubMedGoogle Scholar
  70. 70.
    Masood F. Polymeric nanoparticles for targeted drug delivery system for cancer therapy. Mater Sci Eng C. 2016;60:569–78.CrossRefGoogle Scholar
  71. 71.
    Chen Y, Liu L. Modern methods for delivery of drugs across the blood–brain barrier. Adv Drug Deliv Rev. 2012;64(7):640–65.PubMedCrossRefGoogle Scholar
  72. 72.
    Huwyler J, Wu D, Pardridge WM. Brain drug delivery of small molecules using immunoliposomes. Proc Natl Acad Sci. 1996;93(24):14164–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Du J, Lu W-L, Ying X, Liu Y, Du P, Tian W, et al. Dual-targeting topotecan liposomes modified with tamoxifen and wheat germ agglutinin significantly improve drug transport across the blood−brain barrier and survival of brain tumor-bearing animals. Mol Pharm. 2009;6(3):905–17.PubMedCrossRefGoogle Scholar
  74. 74.
    Re F, Cambianica I, Zona C, Sesana S, Gregori M, Rigolio R, et al. Functionalization of liposomes with ApoE-derived peptides at different density affects cellular uptake and drug transport across a blood-brain barrier model. Nanomedicine. 2011;7(5):551–9.PubMedCrossRefGoogle Scholar
  75. 75.
    Pinzón-Daza M, Garzón R, Couraud P, Romero I, Weksler B, Ghigo D, et al. The association of statins plus LDL receptor-targeted liposome-encapsulated doxorubicin increases in vitro drug delivery across blood-brain barrier cells: new strategy for drug delivery into brain tumours. Br J Pharmacol. 2012;167(7):1431–47.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Chen H, Qin Y, Zhang Q, Jiang W, Tang L, Liu J, et al. Lactoferrin modified doxorubicin-loaded procationic liposomes for the treatment of gliomas. Eur J Pharm Sci. 2011;44(1–2):164–73.PubMedCrossRefGoogle Scholar
  77. 77.
    Huang F-Y, Chen W-J, Lee W-Y, Lo S-T, Lee T-W, Lo J-M. In vitro and in vivo evaluation of lactoferrin-conjugated liposomes as a novel carrier to improve the brain delivery. IJMS. 2013;14(2):2862–74.PubMedCrossRefGoogle Scholar
  78. 78.
    Madhankumar AB, Slagle-Webb B, Wang X, Yang QX, Antonetti DA, Miller PA, et al. Efficacy of interleukin-13 receptor-targeted liposomal doxorubicin in the intracranial brain tumor model. Mol Cancer Ther. 2009;8(3):648–54.PubMedCrossRefGoogle Scholar
  79. 79.
    Shi K, Long Y, Xu C, Wang Y, Qiu Y, Yu Q, et al. Liposomes combined an integrin α v β 3 -specific vector with pH-responsible cell-penetrating property for highly effective Antiglioma therapy through the blood–brain barrier. ACS Appl Mater Interfaces. 2015;7(38):21442–54.PubMedCrossRefGoogle Scholar
  80. 80.
    Qin L, Wang C-Z, Fan H-J, Zhang C-J, Zhang H-W, Lv M-H, et al. A dual-targeting liposome conjugated with transferrin and arginine-glycine-aspartic acid peptide for glioma-targeting therapy. Oncol Lett. 2014;8(5):2000–6.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Lv Q, Li L-M, Han M, Tang X-J, Yao J-N, Ying X-Y, et al. Characteristics of sequential targeting of brain glioma for transferrin-modified cisplatin liposome. Int J Pharm. 2013;444(1–2):1–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Song X, Liu S, Jiang Y, Gu L, Xiao Y, Wang X, et al. Targeting vincristine plus tetrandrine liposomes modified with DSPE-PEG 2000 -transferrin in treatment of brain glioma. Eur J Pharm Sci. 2017;96:129–40.PubMedCrossRefGoogle Scholar
  83. 83.
    Ying X, Wen H, Lu W-L, Du J, Guo J, Tian W, et al. Dual-targeting daunorubicin liposomes improve the therapeutic efficacy of brain glioma in animals. J Control Release. 2010;141(2):183–92.PubMedCrossRefGoogle Scholar
  84. 84.
    Gao J-Q, Lv Q, Li L-M, Tang X-J, Li F-Z, Hu Y-L, et al. Glioma targeting and blood–brain barrier penetration by dual-targeting doxorubincin liposomes. Biomaterials. 2013;34(22):5628–39.PubMedCrossRefGoogle Scholar
  85. 85.
    McNeeley KM, Annapragada A, Bellamkonda RV. Decreased circulation time offsets increased efficacy of PEGylated nanocarriers targeting folate receptors of glioma. Nanotechnology. 2007;18(38):385101.CrossRefGoogle Scholar
  86. 86.
    Alam MI, Beg S, Samad A, Baboota S, Kohli K, Ali J, et al. Strategy for effective brain drug delivery. Eur J Pharm Sci. 2010;40(5):385–403.PubMedCrossRefGoogle Scholar
  87. 87.
    Zhang B, Sun X, Mei H, Wang Y, Liao Z, Chen J, et al. LDLR-mediated peptide-22-conjugated nanoparticles for dual-targeting therapy of brain glioma. Biomaterials. 2013;34(36):9171–82.PubMedCrossRefGoogle Scholar
  88. 88.
    Wang C-X, Huang L-S, Hou L-B, Jiang L, Yan Z-T, Wang Y-L, et al. Antitumor effects of polysorbate-80 coated gemcitabine polybutylcyanoacrylate nanoparticles in vitro and its pharmacodynamics in vivo on C6 glioma cells of a brain tumor model. Brain Res. 2009;1261:91–9.PubMedCrossRefGoogle Scholar
  89. 89.
    Jose S, Sowmya S, Cinu TA, Aleykutty NA, Thomas S, Souto EB. Surface modified PLGA nanoparticles for brain targeting of Bacoside-A. Eur J Pharm Sci. 2014;63:29–35.PubMedCrossRefGoogle Scholar
  90. 90.
    Wagner S, Zensi A, Wien SL, Tschickardt SE, Maier W, Vogel T, et al. Uptake mechanism of ApoE-modified nanoparticles on brain capillary endothelial cells as a blood-brain barrier model. Deli MA, editor. PLoS One. 2012;7(3):e32568.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Su Z, Xing L, Chen Y, Xu Y, Yang F, Zhang C, et al. Lactoferrin-modified poly(ethylene glycol)-grafted BSA nanoparticles as a dual-targeting carrier for treating brain gliomas. Mol Pharm. 2014;11(6):1823–34.PubMedCrossRefGoogle Scholar
  92. 92.
    Xu Y, Asghar S, Yang L, Li H, Wang Z, Ping Q, et al. Lactoferrin-coated polysaccharide nanoparticles based on chitosan hydrochloride/hyaluronic acid/PEG for treating brain glioma. Carbohydr Polym. 2017;157:419–28.PubMedCrossRefGoogle Scholar
  93. 93.
    Shi K, Zhou J, Zhang Q, Gao H, Liu Y, Zong T, et al. Arginine-glycine-aspartic acid-modified lipid-polymer hybrid nanoparticles for docetaxel delivery in glioblastoma multiforme. J Biomed Nanotechnol. 2015;11(3):382–91.PubMedCrossRefGoogle Scholar
  94. 94.
    Wang S. Antitumoral cascade-targeting ligand for IL-6 receptor-mediated gene delivery to glioma. Mol Ther. 2017;25(7):1556–66.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Gao H, Xiong Y, Zhang S, Yang Z, Cao S, Jiang X. RGD and interleukin-13 peptide functionalized nanoparticles for enhanced glioblastoma cells and Neovasculature dual targeting delivery and elevated tumor penetration. Mol Pharm. 2014;11(3):1042–52.PubMedCrossRefGoogle Scholar
  96. 96.
    Jain A, Jain A, Garg NK, Tyagi RK, Singh B, Katare OP, Webster TJ, Soni V. Surface engineered polymeric nanocarriers mediate the delivery of transferrin–methotrexate conjugates for an improved understanding of brain cancer. Acta Biomater. 2015;24:140–51.PubMedCrossRefGoogle Scholar
  97. 97.
    Jain A, Chasoo G, Singh SK, Saxena AK, Jain SK. Transferrin-appended PEGylated nanoparticles for temozolomide delivery to brain: in vitro characterisation. J Microencapsul. 2011;28(1):21–8.PubMedCrossRefGoogle Scholar
  98. 98.
    Cui Y, Xu Q, Chow PK-H, Wang D, Wang C-H. Transferrin-conjugated magnetic silica PLGA nanoparticles loaded with doxorubicin and paclitaxel for brain glioma treatment. Biomaterials. 2013;34(33):8511–20.PubMedCrossRefGoogle Scholar
  99. 99.
    Ghadiri M, Vasheghani-Farahani E, Atyabi F, Kobarfard F, Mohamadyar-Toupkanlou F, Hosseinkhani H. Transferrin-conjugated magnetic dextran-spermine nanoparticles for targeted drug transport across blood-brain barrier: transferrin-conjugated magnetic dextran-spermine nanoparticles. J Biomed Mater Res A. 2017;105(10):2851–64.PubMedCrossRefGoogle Scholar
  100. 100.
    Yan F, Wang Y, He S, Ku S, Gu W, Ye L. Transferrin-conjugated, fluorescein-loaded magnetic nanoparticles for targeted delivery across the blood–brain barrier. J Mater Sci Mater Med. 2013;24(10):2371–9.PubMedCrossRefGoogle Scholar
  101. 101.
    Chang J, Paillard A, Passirani C, Morille M, Benoit J-P, Betbeder D, et al. 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.PubMedCrossRefGoogle Scholar
  102. 102.
    Brioschi AM, Calderoni S, Zara GP, Priano L, Gasco MR, Mauro A. Solid lipid nanoparticles for brain tumors therapy: state of the art and novel challenges. In: Progress in brain research. 2009;180:193–223.Google Scholar
  103. 103.
    Kadari A, Pooja D, Gora RH, Gudem S, Kolapalli VRM, Kulhari H, et al. Design of multifunctional peptide collaborated and docetaxel loaded lipid nanoparticles for antiglioma therapy. Eur J Pharm Biopharm. 2018;132:168–79.PubMedCrossRefGoogle Scholar
  104. 104.
    Kadari A, Pooja D, Gora RH, Gudem S, Kolapalli VRM, Kulhari H, et al. Design of multifunctional peptide collaborated and docetaxel loaded lipid nanoparticles for antiglioma therapy. Eur J Pharm Biopharm. 2018;132:168–79.PubMedCrossRefGoogle Scholar
  105. 105.
    Neves AR, Queiroz JF, Lima SAC, Reis S. Apo E-functionalization of solid lipid nanoparticles enhances brain drug delivery: uptake mechanism and transport pathways. Bioconjug Chem. 2017;28(4):995–1004.PubMedCrossRefGoogle Scholar
  106. 106.
    Kuo Y-C, Lee I-H. Delivery of doxorubicin to glioblastoma multiforme in vitro using solid lipid nanoparticles with surface aprotinin and melanotransferrin antibody for enhanced chemotherapy. J Taiwan Inst Chem Eng. 2016;61:32–45.CrossRefGoogle Scholar
  107. 107.
    Kuo Y-C, Wang I-H. Enhanced delivery of etoposide across the blood–brain barrier to restrain brain tumor growth using melanotransferrin antibody- and tamoxifen-conjugated solid lipid nanoparticles. J Drug Target. 2016;24(7):645–54.PubMedCrossRefGoogle Scholar
  108. 108.
    Jain A, Singhai P, Gurnany E, Updhayay S, Mody N. Transferrin-tailored solid lipid nanoparticles as vectors for site-specific delivery of temozolomide to brain. J Nanopart Res. 2013;15(3):1518.CrossRefGoogle Scholar
  109. 109.
    Kuo Y-C, Liang C-T. Catanionic solid lipid nanoparticles carrying doxorubicin for inhibiting the growth of U87MG cells. Colloids Surf B: Biointerfaces. 2011;85(2):131–7.PubMedCrossRefGoogle Scholar
  110. 110.
    Emami J, Yousefian H, Sadeghi H. Targeted nanostructured lipid carrier for brain delivery of artemisinin: design, preparation, characterization, optimization and cell toxicity. J Pharm Pharm Sci. 2018;21(1s):225s–41s.PubMedCrossRefGoogle Scholar
  111. 111.
    Emami J, Rezazadeh M, Sadeghi H, Khadivar K. Development and optimization of transferrin-conjugated nanostructured lipid carriers for brain delivery of paclitaxel using box–Behnken design. Pharm Dev Technol. 2017;22(3):370–82.PubMedCrossRefGoogle Scholar
  112. 112.
    Meng F, Asghar S, Xu Y, Wang J, Jin X, Wang Z, et al. Design and evaluation of lipoprotein resembling curcumin-encapsulated protein-free nanostructured lipid carrier for brain targeting. Int J Pharm. 2016;506(1–2):46–56.PubMedCrossRefGoogle Scholar
  113. 113.
    Song S, Mao G, Du J, Zhu X. Novel RGD containing, temozolomide-loading nanostructured lipid carriers for glioblastoma multiforme chemotherapy. Drug Deliv. 2016;23(4):1404–8.PubMedCrossRefGoogle Scholar
  114. 114.
    Zhang J, Xiao X, Zhu J, Gao Z, Lai X, Zhu X, et al. Lactoferrin- and RGD-comodified, temozolomide and vincristine-coloaded nanostructured lipid carriers for gliomatosis cerebri combination therapy. Int J Nanomedicine. 2018;13:3039.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Ahn J, Miura Y, Yamada N, Chida T, Liu X, Kim A, et al. Antibody fragment-conjugated polymeric micelles incorporating platinum drugs for targeted therapy of pancreatic cancer. Biomaterials. 2015;39:23–30.PubMedCrossRefGoogle Scholar
  116. 116.
    Noh T, Kook YH, Park C, Youn H, Kim H, Oh ET, et al. Block copolymer micelles conjugated with anti-EGFR antibody for targeted delivery of anticancer drug. J Polym Sci A Polym Chem. 2008;46(22):7321–31.CrossRefGoogle Scholar
  117. 117.
    Zhan C, Li B, Hu L, Wei X, Feng L, Fu W, et al. Micelle-based brain-targeted drug delivery enabled by a nicotine acetylcholine receptor ligand. Angew Chem Int Ed. 2011;50(24):5482–5.CrossRefGoogle Scholar
  118. 118.
    Shen J, Zhan C, Xie C, Meng Q, Gu B, Li C, et al. Poly(ethylene glycol)-block-poly(d, l -lactide acid) micelles anchored with angiopep-2 for brain-targeting delivery. J Drug Target. 2011;19(3):197–203.PubMedCrossRefGoogle Scholar
  119. 119.
    Li A-J, Zheng Y-H, Liu G-D, Liu W-S, Cao P-C, Bu Z-F. Efficient delivery of docetaxel for the treatment of brain tumors by cyclic RGD-tagged polymeric micelles. Mol Med Rep. 2015;11(4):3078–86.PubMedCrossRefGoogle Scholar
  120. 120.
    Zhan C, Gu B, Xie C, Li J, Liu Y, Lu W. Cyclic RGD conjugated poly(ethylene glycol)-co-poly(lactic acid) micelle enhances paclitaxel anti-glioblastoma effect. J Control Release. 2010;143(1):136–42.PubMedCrossRefGoogle Scholar
  121. 121.
    Huang Y, Liu W, Gao F, Fang X, Chen Y. c(RGDyK)-decorated pluronic micelles for enhanced doxorubicin and paclitaxel delivery to brain glioma. Int J Nanomed. 2016;11:1629.Google Scholar
  122. 122.
    Zhang P, Hu L, Yin Q, Feng L, Li Y. Transferrin-modified c[RGDfK]-paclitaxel loaded hybrid micelle for sequential blood-brain barrier penetration and glioma targeting therapy. Mol Pharm. 2012;9(6):1590–8.PubMedCrossRefGoogle Scholar
  123. 123.
    Zhang P, Hu L, Yin Q, Zhang Z, Feng L, Li Y. Transferrin-conjugated polyphosphoester hybrid micelle loading paclitaxel for brain-targeting delivery: synthesis, preparation and in vivo evaluation. J Control Release. 2012;159(3):429–34.PubMedCrossRefGoogle Scholar
  124. 124.
    Agrawal P, Sonali, Singh RP, Sharma G, Mehata AK, Singh S, et al. Bioadhesive micelles of d -α-tocopherol polyethylene glycol succinate 1000: synergism of chitosan and transferrin in targeted drug delivery. Colloids Surf B Biointerfaces. 2017;152:277–288.PubMedCrossRefGoogle Scholar
  125. 125.
    Ren W, Chang J, Yan C, Qian X, Long L, He B, et al. 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.PubMedCrossRefGoogle Scholar
  126. 126.
    Niu J, Wang A, Ke Z, Zheng Z. Glucose transporter and folic acid receptor-mediated Pluronic P105 polymeric micelles loaded with doxorubicin for brain tumor treating. J Drug Target. 2014;22(8):712–23.PubMedCrossRefGoogle Scholar
  127. 127.
    Shinde RL, Devarajan PV. Docosahexaenoic acid–mediated, targeted and sustained brain delivery of curcumin microemulsion. Drug Deliv. 2017;24(1):152–61.PubMedCrossRefGoogle Scholar
  128. 128.
    Muzaffar F, Singh UK, Chauhan L. Review on microemulsion as futuristic drug delivery. Int J Pharm Pharm Sci. 2013;5(3):39–53.Google Scholar
  129. 129.
    Etman SM, Elnaggar YSR, Abdelmonsif DA, Abdallah OY. Oral brain-targeted microemulsion for enhanced Piperine delivery in Alzheimer’s disease therapy: in vitro appraisal, in vivo activity, and nanotoxicity. AAPS PharmSciTech. 2018;19(8):3698–711.PubMedCrossRefGoogle Scholar
  130. 130.
    Harun S, Amin Nordin S, Abd Gani SS, Shamsuddin AF, Basri M, Bin BH. Development of nanoemulsion for efficient brain parenteral delivery of cefuroxime: designs, characterizations, and pharmacokinetics. Int J Nanomedicine. 2018;13:2571.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Prabhakar K, Afzal SM, Surender G, Kishan V. Tween 80 containing lipid nanoemulsions for delivery of indinavir to brain. Acta Pharm Sin B. 2013;3(5):345–53.CrossRefGoogle Scholar
  132. 132.
    Vyas TK, Shahiwala A, Amiji MM. Improved oral bioavailability and brain transport of Saquinavir upon administration in novel nanoemulsion formulations. Int J Pharm. 2008;347(1–2):93–101.PubMedCrossRefGoogle Scholar
  133. 133.
    Han L, Huang R, Liu S, Huang S, Jiang C. Peptide-conjugated PAMAM for targeted doxorubicin delivery to transferrin receptor overexpressed tumors. Mol Pharm. 2010;7(6):2156–65.PubMedCrossRefGoogle Scholar
  134. 134.
    Hao B, Gao S, Li J, Jiang C, Hong B. Plasmid pORF-hTRAIL targeting to glioma using transferrin-modified polyamidoamine dendrimer. Drug Des Devel Ther. 2016;10:1.PubMedGoogle Scholar
  135. 135.
    He H, Li Y, Jia X-R, Du J, Ying X, Lu W-L, et al. PEGylated poly(amidoamine) dendrimer-based dual-targeting carrier for treating brain tumors. Biomaterials. 2011;32(2):478–87.PubMedCrossRefGoogle Scholar
  136. 136.
    Huang R-Q, Qu Y-H, Ke W-L, Zhu J-H, Pei Y-Y, Jiang C. Efficient gene delivery targeted to the brain using a transferrin-conjugated polyethyleneglycol-modified polyamidoamine dendrimer. FASEB J. 2007;21(4):1117–25.PubMedCrossRefGoogle Scholar
  137. 137.
    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):3899–908.PubMedCrossRefGoogle Scholar
  138. 138.
    Somani S, Blatchford DR, Millington O, Stevenson ML, Dufès C. Transferrin-bearing polypropylenimine dendrimer for targeted gene delivery to the brain. J Control Release. 2014;188:78–86.PubMedCrossRefGoogle Scholar
  139. 139.
    Yuan Q, Fu Y, Kao WJ, Janigro D, Yang H. Transbuccal delivery of CNS therapeutic nanoparticles: synthesis, characterization, and in vitro permeation studies. ACS Chem Neurosci. 2011;2(11):676–83.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Sun T, Wu H, Li Y, Huang Y, Yao L, Chen X, et al. Targeting transferrin receptor delivery of temozolomide for a potential glioma stem cell-mediated therapy. Oncotarget. 2017;8(43):74451.PubMedPubMedCentralGoogle Scholar
  141. 141.
    Ke W, Shao K, Huang R, Han L, Liu Y, Li J, et al. Gene delivery targeted to the brain using an Angiopep-conjugated polyethyleneglycol-modified polyamidoamine dendrimer. Biomaterials. 2009;30(36):6976–85.PubMedCrossRefPubMedCentralGoogle Scholar
  142. 142.
    Somani S, Robb G, Pickard BS, Dufès C. Enhanced gene expression in the brain following intravenous administration of lactoferrin-bearing polypropylenimine dendriplex. J Control Release. 2015;217:235–42.PubMedCrossRefGoogle Scholar
  143. 143.
    Liu Y, Huang R, Han L, Ke W, Shao K, Ye L, et al. Brain-targeting gene delivery and cellular internalization mechanisms for modified rabies virus glycoprotein RVG29 nanoparticles. Biomaterials. 2009;30(25):4195–202.PubMedCrossRefGoogle Scholar
  144. 144.
    Gao H, Qian J, Cao S, Yang Z, Pang Z, Pan S, et al. Precise glioma targeting of and penetration by aptamer and peptide dual-functioned nanoparticles. Biomaterials. 2012;33(20):5115–23.PubMedCrossRefGoogle Scholar
  145. 145.
    Delač M, Motaln H, Ulrich H, Lah TT. Aptamer for imaging and therapeutic targeting of brain tumor glioblastoma: aptamers in glioblastoma. Cytometry. 2015;87(9):806–16.PubMedCrossRefGoogle Scholar
  146. 146.
    Guo J, Gao X, Su L, Xia H, Gu G, Pang Z, et al. Aptamer-functionalized PEG–PLGA nanoparticles for enhanced anti-glioma drug delivery. Biomaterials. 2011;32(31):8010–20.PubMedCrossRefGoogle Scholar
  147. 147.
    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(11):3324–33.PubMedCrossRefGoogle Scholar
  148. 148.
    Lu Y-J, Wei K-C, Ma C-CM, Yang S-Y, Chen J-P. Dual targeted delivery of doxorubicin to cancer cells using folate-conjugated magnetic multi-walled carbon nanotubes. Colloids Surf B: Biointerfaces. 2012;89:1–9.PubMedCrossRefGoogle Scholar
  149. 149.
    Li S, Peng Z, Dallman J, Baker J, Othman AM, Blackwelder PL, et al. Crossing the blood–brain–barrier with transferrin conjugated carbon dots: a zebrafish model study. Colloids Surf B: Biointerfaces. 2016;145:251–6.PubMedCrossRefGoogle Scholar
  150. 150.
    Li S, Amat D, Peng Z, Vanni S, Raskin S, De Angulo G, et al. Transferrin conjugated nontoxic carbon dots for doxorubicin delivery to target pediatric brain tumor cells. Nanoscale. 2016;8(37):16662–9.PubMedCrossRefGoogle Scholar
  151. 151.
    Huang R, Han L, Li J, Liu S, Shao K, Kuang Y, et al. Chlorotoxin-modified macromolecular contrast agent for MRI tumor diagnosis. Biomaterials. 2011;32(22):5177–86.PubMedCrossRefGoogle Scholar
  152. 152.
    Jiang W, Xie H, Ghoorah D, Shang Y, Shi H, Liu F, et al. Conjugation of functionalized SPIONs with transferrin for targeting and imaging brain glial tumors in rat model. Brechbiel MW, editor. PLoS One. 2012;7(5):e37376.PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    Xie H, Zhu Y, Jiang W, Zhou Q, Yang H, Gu N, et al. Lactoferrin-conjugated superparamagnetic iron oxide nanoparticles as a specific MRI contrast agent for detection of brain glioma in vivo. Biomaterials. 2011;32(2):495–502.PubMedCrossRefGoogle Scholar
  154. 154.
    Yan H, Wang J, Yi P, Lei H, Zhan C, Xie C, et al. Imaging brain tumor by dendrimer-based optical/paramagnetic nanoprobe across the blood-brain barrier. Chem Commun. 2011;47(28):8130–2.CrossRefGoogle Scholar
  155. 155.
    Cai W, Shin D-W, Chen K, Gheysens O, Cao Q, Wang SX, et al. Peptide-labeled near-infrared quantum dots for imaging tumor vasculature in living subjects. Nano Lett. 2006;6(4):669–76.PubMedCrossRefGoogle Scholar
  156. 156.
    Cui L, Lin Q, Jin CS, Jiang W, Huang H, Ding L, et al. A PEGylation-free biomimetic porphyrin nanoplatform for personalized cancer theranostics. ACS Nano. 2015;9(4):4484–95.PubMedCrossRefGoogle Scholar
  157. 157.
    Dixit S, Miller K, Zhu Y, McKinnon E, Novak T, Kenney ME, et al. Dual receptor-targeted theranostic nanoparticles for localized delivery and activation of photodynamic therapy drug in glioblastomas. Mol Pharm. 2015;12(9):3250–60.PubMedPubMedCentralCrossRefGoogle Scholar
  158. 158.
    Rajora MA, Ding L, Valic M, Jiang W, Overchuk M, Chen J, et al. Tailored theranostic apolipoprotein E3 porphyrin-lipid nanoparticles target glioblastoma. Chem Sci. 2017;8(8):5371–84.PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Yoo B, Ifediba MA, Ghosh S, Medarova Z, Moore A. Combination treatment with theranostic nanoparticles for glioblastoma sensitization to TMZ. Mol Imaging Biol. 2014;16(5):680–9.PubMedCrossRefGoogle Scholar
  160. 160.
    Kuang Y, Zhang K, Cao Y, Chen X, Wang K, Liu M, et al. Hydrophobic IR-780 dye encapsulated in cRGD-conjugated solid lipid nanoparticles for NIR imaging-guided photothermal therapy. ACS Appl Mater Interfaces. 2017;9(14):12217–26.PubMedCrossRefGoogle Scholar
  161. 161.
    Fang J-Y, Wen C-J, Zhang LW, Al-Suwayeh SA, Yen T-C. Theranostic liposomes loaded with quantum dots and apomorphine for brain targeting and bioimaging. Int J Nanomed. 2012;7:1599.CrossRefGoogle Scholar
  162. 162.
    Cytotoxic T cells and interleukin-2 in treating adult patients with recurrent brain tumors – full text view – ClinicalTrials.gov [Internet]. [cited 2019 Jun 16]. Available from: https://clinicaltrials.gov/ct2/show/NCT00002572.
  163. 163.
    ANG1005 in breast cancer patients with recurrent brain metastases – full text view – ClinicalTrials.gov [Internet]. [cited 2019 Jun 16]. Available from: https://clinicaltrials.gov/ct2/show/NCT02048059.
  164. 164.
    Cellular immunotherapy study for brain cancer – full text view – ClinicalTrials.gov [Internet]. [cited 2019 Jun 16]. Available from: https://clinicaltrials.gov/ct2/show/NCT01144247.
  165. 165.
    IL-4(38-37)-PE38KDEL immunotoxin in treating patients with recurrent malignant astrocytoma – full text view – ClinicalTrials.gov [Internet]. [cited 2019 Jun 16]. Available from: https://clinicaltrials.gov/ct2/show/NCT00003842.
  166. 166.
    Study of therapy with TransMID™ compared to best standard of care in patients with glioblastoma multiforme – full text view – ClinicalTrials.gov [Internet]. [cited 2019 Jun 16]. Available from: https://clinicaltrials.gov/ct2/show/NCT00083447.
  167. 167.
    T cells expressing HER2-specific chimeric antigen receptors(CAR) for patients with HER2-positive CNS tumors – full text view – ClinicalTrials.gov [Internet]. [cited 2019 Jun 16]. Available from: https://clinicaltrials.gov/ct2/show/NCT02442297.
  168. 168.
    Chemotherapy and vaccine therapy followed by bone marrow or peripheral stem cell transplantation and interleukin-2 in treating patients with recurrent or refractory brain cancer – full text view – ClinicalTrials.gov [Internet]. [cited 2019 Jun 16]. Available from: https://clinicaltrials.gov/ct2/show/NCT00014573.
  169. 169.
    EGFRBi-armed autologous T cells in treating patients with recurrent or refractory glioblastoma – full text view – ClinicalTrials.gov [Internet]. [cited 2019 Jun 16]. Available from: https://clinicaltrials.gov/ct2/show/NCT02521090.
  170. 170.
    A study of ABT-414 in subjects with newly diagnosed glioblastoma (GBM) with epidermal growth factor receptor (EGFR) amplification – full text view – ClinicalTrials.gov [Internet]. [cited 2019 Jun 16]. Available from: https://clinicaltrials.gov/ct2/show/NCT02573324.

Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Rijo John
    • 1
  • Heero Vaswani
    • 1
  • Prajakta Dandekar
    • 2
  • Padma V. Devarajan
    • 2
    Email author
  1. 1.Department of Pharmaceutical Sciences &TechnologyInstitute of Chemical Technology, MatungaMumbaiIndia
  2. 2.Department of Pharmaceutical SciencesInsitute of Chemical Technology, Deemed University, Elite Status and Centre of Excellence, Government of MaharashtraMumbaiIndia

Personalised recommendations