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Surface-Modified Nanodrug Carriers for Brain Cancer Treatment

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Nanotherapy for Brain Tumor Drug Delivery

Part of the book series: Neuromethods ((NM,volume 163))

Abstract

Brain cancers, especially glioblastomas (GBM), are among the most deadly human tumors due to high proliferation rates, invasion into functioning brain parenchyma, genomic instability, cellular and molecular heterogeneity, and more. The brain exhibits a uniquely complex physiology and utilizes specialized mechanisms, including blood-brain barrier formation, to prevent the influx of many molecules from the external environment, including most systemically administered chemotherapeutics. Nanoparticles are particularly promising for drug delivery to the brain due to their small size, ability to encapsulate drugs, controlled drug release profiles, and their potential to be actively targeted to cells and structures within the brain. In this chapter, we outline why targeted nanotechnology is poised to overcome the brain’s specialized barriers to drug delivery and introduce some of the cell surface molecules, including the fibroblast growth factor-inducible 14 (Fn14) receptor, employed for targeting nanodrug carriers to GBM. Importantly, we review an advanced nanotherapeutic formulation developed by our team designed for optimal (1) brain tumor accumulation and penetration by reducing nonspecific interactions with blood plasma proteins and extracellular matrix proteins (off-target effects) and (2) brain tumor targeting by increasing specific interactions with targeting molecules that are overexpressed on cancer cells (on-target effects). These decreased adhesivity, receptor-targeted (DART) nanoparticles were developed for GBM treatment by balancing and maintaining low nonspecific adhesivity and high Fn14 receptor binding.

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References

  1. Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359(5):492–507

    Article  CAS  PubMed  Google Scholar 

  2. Gladson CL, Prayson RA, Liu WM (2010) The pathobiology of glioma tumors. Annu Rev Pathol 5:33–50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Cloughesy TF, Cavenee WK, Mischel PS (2014) Glioblastoma: from molecular pathology to targeted treatment. Annu Rev Pathol 9:1–25

    Article  CAS  PubMed  Google Scholar 

  4. Aldape K et al (2015) Glioblastoma: pathology, molecular mechanisms and markers. Acta Neuropathol 129(6):829–848

    Article  CAS  PubMed  Google Scholar 

  5. Louis DN et al (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131(6):803–820

    Article  PubMed  Google Scholar 

  6. Stupp R et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996

    Article  CAS  PubMed  Google Scholar 

  7. Woodworth GF et al (2014) Emerging insights into barriers to effective brain tumor therapeutics. Front Oncol 4:126

    Article  PubMed  PubMed Central  Google Scholar 

  8. Galicich JH, French LA, Melby JC (1961) Use of dexamethasone in treatment of cerebral edema associated with brain tumors. J Lancet 81:46–53

    CAS  PubMed  Google Scholar 

  9. Shibamoto Y et al (1990) Supratentorial malignant glioma: an analysis of radiation therapy in 178 cases. Radiother Oncol 18(1):9–17

    Article  CAS  PubMed  Google Scholar 

  10. Stewart LA (2002) Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet 359(9311):1011–1018

    Article  CAS  PubMed  Google Scholar 

  11. Brem H et al (1995) Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group. Lancet 345(8956):1008–1012

    Article  CAS  PubMed  Google Scholar 

  12. Brem H et al (1995) The safety of interstitial chemotherapy with BCNU-loaded polymer followed by radiation therapy in the treatment of newly diagnosed malignant gliomas: phase I trial. J Neuro-Oncol 26(2):111–123

    Article  CAS  Google Scholar 

  13. Valtonen S et al (1997) Interstitial chemotherapy with carmustine-loaded polymers for high-grade gliomas: a randomized double-blind study. Neurosurgery 41(1):44–48; discussion 48-9

    Article  CAS  PubMed  Google Scholar 

  14. Westphal M et al (2003) A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro-Oncology 5(2):79–88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Westphal M et al (2006) Gliadel wafer in initial surgery for malignant glioma: long-term follow-up of a multicenter controlled trial. Acta Neurochir 148(3):269–275. discussion 275

    Article  CAS  PubMed  Google Scholar 

  16. Giese A et al (2003) Cost of migration: invasion of malignant gliomas and implications for treatment. J Clin Oncol 21(8):1624–1636

    Article  CAS  PubMed  Google Scholar 

  17. Vehlow A, Cordes N (2013) Invasion as target for therapy of glioblastoma multiforme. Biochim Biophys Acta 1836(2):236–244

    CAS  PubMed  Google Scholar 

  18. van Tellingen O et al (2015) Overcoming the blood-brain tumor barrier for effective glioblastoma treatment. Drug Resist Updat 19:1–12

    Article  PubMed  Google Scholar 

  19. Armulik A et al (2010) Pericytes regulate the blood-brain barrier. Nature 468(7323):557–561

    Article  CAS  PubMed  Google Scholar 

  20. Pardridge WM (2005) The blood-brain barrier: bottleneck in brain drug development. NeuroRx 2(1):3–14

    Article  PubMed  PubMed Central  Google Scholar 

  21. Obermeier B, Daneman R, Ransohoff RM (2013) Development, maintenance and disruption of the blood-brain barrier. Nat Med 19(12):1584–1596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Groothuis DR (2000) The blood-brain and blood-tumor barriers: a review of strategies for increasing drug delivery. Neuro-Oncology 2(1):45–59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Tate MC, Aghi MK (2009) Biology of angiogenesis and invasion in glioma. Neurotherapeutics 6(3):447–457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Plog BA, Nedergaard M (2018) The Glymphatic system in central nervous system health and disease: past, present, and future. Annu Rev Pathol 13:379–394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Louveau A et al (2015) Structural and functional features of central nervous system lymphatic vessels. Nature 523(7560):337–341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bellail AC et al (2004) Microregional extracellular matrix heterogeneity in brain modulates glioma cell invasion. Int J Biochem Cell Biol 36(6):1046–1069

    Article  CAS  PubMed  Google Scholar 

  27. Nicholson C, Tao L (1993) Hindered diffusion of high molecular weight compounds in brain extracellular microenvironment measured with integrative optical imaging. Biophys J 65(6):2277–2290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Diaz RJ et al (2014) Focused ultrasound delivery of Raman nanoparticles across the blood-brain barrier: potential for targeting experimental brain tumors. Nanomedicine 10(5):1075–1087

    Article  CAS  PubMed  Google Scholar 

  29. Alonso MJ (2004) Nanomedicines for overcoming biological barriers. Biomed Pharmacother 58(3):168–172

    Article  PubMed  CAS  Google Scholar 

  30. Jain RK, Stylianopoulos T (2010) Delivering nanomedicine to solid tumors. Nat Rev Clin Oncol 7(11):653–664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hersh DS et al (2016) Evolving drug delivery strategies to overcome the blood brain barrier. Curr Pharm Des 22(9):1177–1193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Calvo P et al (2001) Long-circulating PEGylated polycyanoacrylate nanoparticles as new drug carrier for brain delivery. Pharm Res 18(8):1157–1166

    Article  CAS  PubMed  Google Scholar 

  33. Blanco E, Shen H, Ferrari M (2015) Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol 33(9):941–951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Wadajkar AS et al (2017) Tumor-targeted nanotherapeutics: overcoming treatment barriers for glioblastoma. Wiley Interdiscip Rev Nanomed Nanobiotechnol 9(4)

    Google Scholar 

  35. Pourgholi F et al (2016) Nanoparticles: novel vehicles in treatment of glioblastoma. Biomed Pharmacother 77:98–107

    Article  CAS  PubMed  Google Scholar 

  36. Householder KT et al (2015) Intravenous delivery of camptothecin-loaded PLGA nanoparticles for the treatment of intracranial glioma. Int J Pharm 479(2):374–380

    Article  CAS  PubMed  Google Scholar 

  37. Ambruosi A et al (2006) Biodistribution of polysorbate 80-coated doxorubicin-loaded [14C]-poly(butyl cyanoacrylate) nanoparticles after intravenous administration to glioblastoma-bearing rats. J Drug Target 14(2):97–105

    Article  CAS  PubMed  Google Scholar 

  38. Nance E et al (2014) Non-invasive delivery of stealth, brain-penetrating nanoparticles across the blood-brain barrier using MRI-guided focused ultrasound. J Control Release 189:123–132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Byrne JD, Betancourt T, Brannon-Peppas L (2008) Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev 60(15):1615–1626

    Article  CAS  PubMed  Google Scholar 

  40. Peer D et al (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2(12):751–760

    Article  CAS  PubMed  Google Scholar 

  41. Yang Z et al (2010) A review of nanoparticle functionality and toxicity on the central nervous system. J R Soc Interface 7(Suppl 4):S411–S422

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Cheng Y et al (2014) Blood-brain barrier permeable gold nanoparticles: An efficient delivery platform for enhanced malignant glioma therapy and imaging. Small 10(24):5137–5150

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Barbu E et al (2009) The potential for nanoparticle-based drug delivery to the brain: overcoming the blood-brain barrier. Expert Opin Drug Deliv 6(6):553–565

    Article  CAS  PubMed  Google Scholar 

  44. Kreuter J et al (2002) Apolipoprotein-mediated transport of nanoparticle-bound drugs across the blood-brain barrier. J Drug Target 10(4):317–325

    Article  CAS  PubMed  Google Scholar 

  45. Zensi A et al (2009) Albumin nanoparticles targeted with Apo E enter the CNS by transcytosis and are delivered to neurones. J Control Release 137(1):78–86

    Article  CAS  PubMed  Google Scholar 

  46. Ren T et al (2009) Preparation and therapeutic efficacy of polysorbate-80-coated amphotericin B/PLA-b-PEG nanoparticles. J Biomater Sci Polym Ed 20(10):1369–1380

    Article  CAS  PubMed  Google Scholar 

  47. Samad A, Sultana Y, Aqil M (2007) Liposomal drug delivery systems: an update review. Curr Drug Deliv 4(4):297–305

    Article  CAS  PubMed  Google Scholar 

  48. Chastagner P et al (2015) Phase I study of non-pegylated liposomal doxorubicin in children with recurrent/refractory high-grade glioma. Cancer Chemother Pharmacol 76(2):425–432

    Article  CAS  PubMed  Google Scholar 

  49. Fabel K et al (2001) Long-term stabilization in patients with malignant glioma after treatment with liposomal doxorubicin. Cancer 92(7):1936–1942

    Article  CAS  PubMed  Google Scholar 

  50. Linot B et al (2014) Use of liposomal doxorubicin-cyclophosphamide combination in breast cancer patients with brain metastases: a monocentric retrospective study. J Neuro-Oncol 117(2):253–259

    Article  CAS  Google Scholar 

  51. Qin J et al (2014) cRGD mediated liposomes enhanced antidepressant-like effects of edaravone in rats. Eur J Pharm Sci 58:63–71

    Article  CAS  PubMed  Google Scholar 

  52. Ying X et al (2010) Dual-targeting daunorubicin liposomes improve the therapeutic efficacy of brain glioma in animals. J Control Release 141(2):183–192

    Article  CAS  PubMed  Google Scholar 

  53. Padfield E, Ellis HP, Kurian KM (2015) Current therapeutic advances targeting EGFR and EGFRvIII in glioblastoma. Front Oncol 5:5

    Article  PubMed  PubMed Central  Google Scholar 

  54. Eller JL et al (2002) Activity of anti-epidermal growth factor receptor monoclonal antibody C225 against glioblastoma multiforme. Neurosurgery 51(4):1005–1013; discussion 1013-4

    PubMed  Google Scholar 

  55. Kaluzova M et al (2015) Targeted therapy of glioblastoma stem-like cells and tumor non-stem cells using cetuximab-conjugated iron-oxide nanoparticles. Oncotarget 6(11):8788–8806

    Article  PubMed  PubMed Central  Google Scholar 

  56. An Z et al (2018) Epidermal growth factor receptor and EGFRvIII in glioblastoma: signaling pathways and targeted therapies. Oncogene 37(12):1561–1575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Frederick L et al (2000) Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas. Cancer Res 60(5):1383–1387

    CAS  PubMed  Google Scholar 

  58. Hadjipanayis CG et al (2010) EGFRvIII antibody-conjugated iron oxide nanoparticles for magnetic resonance imaging-guided convection-enhanced delivery and targeted therapy of glioblastoma. Cancer Res 70(15):6303–6312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kim C, Ye F, Ginsberg MH (2011) Regulation of integrin activation. Annu Rev Cell Dev Biol 27:321–345

    Article  CAS  PubMed  Google Scholar 

  60. Mattern RH et al (2005) Glioma cell integrin expression and their interactions with integrin antagonists: Research Article. Cancer Ther 3a:325–340

    PubMed  PubMed Central  Google Scholar 

  61. Reardon DA et al (2008) Cilengitide: an integrin-targeting arginine-glycine-aspartic acid peptide with promising activity for glioblastoma multiforme. Expert Opin Investig Drugs 17(8):1225–1235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Jiang X et al (2013) Integrin-facilitated transcytosis for enhanced penetration of advanced gliomas by poly(trimethylene carbonate)-based nanoparticles encapsulating paclitaxel. Biomaterials 34(12):2969–2979

    Article  CAS  PubMed  Google Scholar 

  63. 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(5):629–640

    Article  CAS  PubMed  Google Scholar 

  64. Rosager AM et al (2017) Transferrin receptor-1 and ferritin heavy and light chains in astrocytic brain tumors: expression and prognostic value. PLoS One 12(8):e0182954

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Pang Z et al (2011) Enhanced intracellular delivery and chemotherapy for glioma rats by transferrin-conjugated biodegradable polymersomes loaded with doxorubicin. Bioconjug Chem 22(6):1171–1180

    Article  CAS  PubMed  Google Scholar 

  66. Lam FC et al (2018) Enhanced efficacy of combined temozolomide and bromodomain inhibitor therapy for gliomas using targeted nanoparticles. Nat Commun 9(1):1991

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Lillis AP, Mikhailenko I, Strickland DK (2005) Beyond endocytosis: LRP function in cell migration, proliferation and vascular permeability. J Thromb Haemost 3(8):1884–1893

    Article  CAS  PubMed  Google Scholar 

  68. Pang Z et al (2010) Lactoferrin-conjugated biodegradable polymersome holding doxorubicin and tetrandrine for chemotherapy of glioma rats. Mol Pharm 7(6):1995–2005

    Article  CAS  PubMed  Google Scholar 

  69. Ruan S et al (2015) Tumor microenvironment sensitive doxorubicin delivery and release to glioma using angiopep-2 decorated gold nanoparticles. Biomaterials 37:425–435

    Article  CAS  PubMed  Google Scholar 

  70. Benarroch EE (2014) Brain glucose transporters: implications for neurologic disease. Neurology 82(15):1374–1379

    Article  PubMed  Google Scholar 

  71. Patching SG (2017) Glucose transporters at the blood-brain barrier: function, regulation and gateways for drug delivery. Mol Neurobiol 54(2):1046–1077

    Article  CAS  PubMed  Google Scholar 

  72. Devraj K et al (2011) GLUT-1 glucose transporters in the blood-brain barrier: differential phosphorylation. J Neurosci Res 89(12):1913–1925

    Article  CAS  PubMed  Google Scholar 

  73. Jiang X et al (2014) Nanoparticles of 2-deoxy-D-glucose functionalized poly(ethylene glycol)-co-poly(trimethylene carbonate) for dual-targeted drug delivery in glioma treatment. Biomaterials 35(1):518–529

    Article  CAS  PubMed  Google Scholar 

  74. Oliveira R et al (2005) Contribution of gap junctional communication between tumor cells and astroglia to the invasion of the brain parenchyma by human glioblastomas. BMC Cell Biol 6(1):7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Schulz R et al (2015) Connexin 43 is an emerging therapeutic target in ischemia/reperfusion injury, cardioprotection and neuroprotection. Pharmacol Ther 153:90–106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Bates DC et al (2007) Connexin43 enhances glioma invasion by a mechanism involving the carboxy terminus. Glia 55(15):1554–1564

    Article  PubMed  Google Scholar 

  77. Chekhonin VP et al (2012) Targeted delivery of liposomal nanocontainers to the peritumoral zone of glioma by means of monoclonal antibodies against GFAP and the extracellular loop of Cx43. Nanomedicine 8(1):63–70

    Article  CAS  PubMed  Google Scholar 

  78. Cheng E et al (2013) TWEAK/Fn14 Axis-targeted therapeutics: moving basic science discoveries to the clinic. Front Immunol 4:473

    Article  PubMed  PubMed Central  Google Scholar 

  79. Winkles JA (2008) The TWEAK-Fn14 cytokine-receptor axis: discovery, biology and therapeutic targeting. Nat Rev Drug Discov 7(5):411–425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Burkly LC (2014) TWEAK/Fn14 axis: the current paradigm of tissue injury-inducible function in the midst of complexities. Semin Immunol 26(3):229–236

    Article  CAS  PubMed  Google Scholar 

  81. Burkly LC, Michaelson JS, Zheng TS (2011) TWEAK/Fn14 pathway: an immunological switch for shaping tissue responses. Immunol Rev 244(1):99–114

    Article  CAS  PubMed  Google Scholar 

  82. Perez JG et al (2016) The TWEAK receptor Fn14 is a potential cell surface portal for targeted delivery of glioblastoma therapeutics. Oncogene 35(17):2145–2155

    Article  CAS  PubMed  Google Scholar 

  83. Tran NL et al (2003) The human Fn14 receptor gene is up-regulated in migrating glioma cells in vitro and overexpressed in advanced glial tumors. Am J Pathol 162(4):1313–1321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Tran NL et al (2006) Increased fibroblast growth factor-inducible 14 expression levels promote glioma cell invasion via Rac1 and nuclear factor-kappaB and correlate with poor patient outcome. Cancer Res 66(19):9535–9542

    Article  CAS  PubMed  Google Scholar 

  85. Fortin SP et al (2012) Cdc42 and the guanine nucleotide exchange factors Ect2 and trio mediate Fn14-induced migration and invasion of glioblastoma cells. Mol Cancer Res 10(7):958–968

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Hersh DS et al (2018) Differential expression of the TWEAK receptor Fn14 in IDH1 wild-type and mutant gliomas. J Neuro-Oncol 138(2):241–250

    Article  CAS  Google Scholar 

  87. Hersh DS et al (2018) The TNF receptor family member Fn14 is highly expressed in recurrent glioblastoma and in GBM patient-derived xenografts with acquired temozolomide resistance. Neuro-Oncology 20(10):1321–1330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Bouras A, Kaluzova M, Hadjipanayis CG (2015) Radiosensitivity enhancement of radioresistant glioblastoma by epidermal growth factor receptor antibody-conjugated iron-oxide nanoparticles. J Neuro-Oncol 124(1):13–22

    Article  CAS  Google Scholar 

  89. Jiang X et al (2011) Self-aggregated pegylated poly (trimethylene carbonate) nanoparticles decorated with c(RGDyK) peptide for targeted paclitaxel delivery to integrin-rich tumors. Biomaterials 32(35):9457–9469

    Article  CAS  PubMed  Google Scholar 

  90. Jiang X et al (2013) Solid tumor penetration by integrin-mediated pegylated poly(trimethylene carbonate) nanoparticles loaded with paclitaxel. Biomaterials 34(6):1739–1746

    Article  CAS  PubMed  Google Scholar 

  91. Wadajkar AS et al (2017) Decreased non-specific adhesivity, receptor targeted (DART) nanoparticles exhibit improved dispersion, cellular uptake, and tumor retention in invasive gliomas. J Control Release 267:144–153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. 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(15):3899–3908

    Article  CAS  PubMed  Google Scholar 

  93. Porru M et al (2014) Medical treatment of orthotopic glioblastoma with transferrin-conjugated nanoparticles encapsulating zoledronic acid. Oncotarget 5(21):10446–10459

    Article  PubMed  PubMed Central  Google Scholar 

  94. Kim SS et al (2014) The clinical potential of targeted nanomedicine: delivering to cancer stem-like cells. Mol Ther 22(2):278–291

    Article  CAS  PubMed  Google Scholar 

  95. Jain A et al (2015) Surface engineered polymeric nanocarriers mediate the delivery of transferrin-methotrexate conjugates for an improved understanding of brain cancer. Acta Biomater 24:140–151

    Article  CAS  PubMed  Google Scholar 

  96. Kim SS et al (2015) Encapsulation of temozolomide in a tumor-targeting nanocomplex enhances anti-cancer efficacy and reduces toxicity in a mouse model of glioblastoma. Cancer Lett 369(1):250–258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Xin H et al (2012) Anti-glioblastoma efficacy and safety of paclitaxel-loading Angiopep-conjugated dual targeting PEG-PCL nanoparticles. Biomaterials 33(32):8167–8176

    Article  CAS  PubMed  Google Scholar 

  98. Thorne RG, Nicholson C (2006) In vivo diffusion analysis with quantum dots and dextrans predicts the width of brain extracellular space. Proc Natl Acad Sci U S A 103(14):5567–5572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Nance EA et al (2012) A dense poly(ethylene glycol) coating improves penetration of large polymeric nanoparticles within brain tissue. Sci Transl Med 4(149):149ra119

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Dancy JG et al (2016) Non-specific binding and steric hindrance thresholds for penetration of particulate drug carriers within tumor tissue. J Control Release 238:139–148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Schneider CS et al (2015) Minimizing the non-specific binding of nanoparticles to the brain enables active targeting of Fn14-positive glioblastoma cells. Biomaterials 42:42–51

    Article  CAS  PubMed  Google Scholar 

  102. Cheng CJ et al (2015) A holistic approach to targeting disease with polymeric nanoparticles. Nat Rev Drug Discov 14(4):239–247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Lesniak MS, Brem H (2004) Targeted therapy for brain tumours. Nat Rev Drug Discov 3(6):499–508

    Article  CAS  PubMed  Google Scholar 

  104. Nance E et al (2014) Brain-penetrating nanoparticles improve paclitaxel efficacy in malignant glioma following local administration. ACS Nano 8(10):10655–10664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Zhang C et al (2017) Convection enhanced delivery of cisplatin-loaded brain penetrating nanoparticles cures malignant glioma in rats. J Control Release 263:112–119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Zhou J et al (2013) Highly penetrative, drug-loaded nanocarriers improve treatment of glioblastoma. Proc Natl Acad Sci U S A 110(29):11751–11756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported, in part, by the National Institutes of Health (R37 CA218617 (A.J.K.), K08 NS09043 (G.F.W.), RO1 NS107813 (G.F.W.), an Institutional Research Grant IRG-97-153-10 (A.S.W.) from the American Cancer Society. A.S.W. and N.P.C. were supported in part by NIH Training Grant T32 CA154274.

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Authors and Affiliations

  1. Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA

    Aniket S. Wadajkar, Nina P. Connolly, Christine P. Carney, Pranjali P. Kanvinde, Jeffrey A. Winkles, Graeme F. Woodworth & Anthony J. Kim

  2. Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA

    Aniket S. Wadajkar, Nina P. Connolly, Christine P. Carney, Pranjali P. Kanvinde, Graeme F. Woodworth & Anthony J. Kim

  3. Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA

    Jeffrey A. Winkles

  4. Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, USA

    Jeffrey A. Winkles

  5. Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA

    Anthony J. Kim

  6. Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USA

    Anthony J. Kim

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  1. Aniket S. Wadajkar
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  2. Nina P. Connolly
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  3. Christine P. Carney
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  4. Pranjali P. Kanvinde
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  5. Jeffrey A. Winkles
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  6. Graeme F. Woodworth
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  7. Anthony J. Kim
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Corresponding authors

Correspondence to Aniket S. Wadajkar or Anthony J. Kim .

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Editors and Affiliations

  1. CONRAD / Eastern Virginia Medical School, Arlington, VA, USA

    Vivek Agrahari

  2. Department of Neurosurgery and Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA

    Anthony Kim

  3. Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Science Center, Oklahoma City, OK, USA

    Vibhuti Agrahari

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Wadajkar, A.S. et al. (2021). Surface-Modified Nanodrug Carriers for Brain Cancer Treatment. In: Agrahari, V., Kim, A., Agrahari, V. (eds) Nanotherapy for Brain Tumor Drug Delivery. Neuromethods, vol 163. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1052-7_5

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  • DOI: https://doi.org/10.1007/978-1-0716-1052-7_5

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