Skip to main content
SpringerLink
Log in

Nano-engineering Nanoparticles for Clinical Use in the Central Nervous System: Clinically Applicable Nanoparticles and Their Potential Uses in the Diagnosis and Treatment of CNS Aliments

  • Chapter
  • First Online:
Nanoengineering Materials for Biomedical Uses

  • 372 Accesses

Abstract

Nano-engineering materials-based diagnosis and treatment of central nervous systems (CNS) ailments has significantly advanced with our deepened knowledge of the pathophysiology of the blood–brain barrier. Unlike other nanoparticle-based tissue engineering strategies, the use of nanoparticles in the CNS must be specifically engineered to circumvent or penetrate the blood–brain barrier, which selectively inhibits drugs and nanoparticles from infiltrating. Current research in the field of CNS nanoparticles has future applications in the fields of diagnostic imaging, drug delivery, specific drug targeting, and tissue regeneration. This chapter highlights some of the nano-engineering of these promising nanoparticle-based biomaterials and their applications in the diagnosis and treatment of brain and spinal cord disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 16.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Pardridge WM. Drug targeting to the brain. Pharm Res. 2007;24(9):1733–44.

    Article  CAS  Google Scholar 

  2. Pardridge WM. Molecular biology of the blood-brain barrier. Mol Biotechnol. 2005;30(1):57–70.

    Article  CAS  Google Scholar 

  3. Popovic N, Brundin P. Therapeutic potential of controlled drug delivery systems in neurodegenerative diseases. Int J Pharm. 2006;314(2):120–6.

    Article  CAS  Google Scholar 

  4. Aloe L, Rocco ML, Omar Balzamino B, Micera A. Nerve growth factor: a focus on neuroscience and therapy. Curr Neuropharmacol. 2015;13(3):294–303.

    Article  CAS  Google Scholar 

  5. Sarkadi B, Homolya L, Szakacs G, Varadi A. Human multidrug resistance ABCB and ABCG transporters: participation in a chemoimmunity defense system. Physiol Rev. 2006;86(4):1179–236.

    Article  CAS  Google Scholar 

  6. Marchesi VT. The role of pinocytic vesicles in the transport of materials across the walls of small blood vessels. Invest. Ophthalmol. 1965;4(6):1111–21.

    CAS  Google Scholar 

  7. Zhou Y, Peng Z, Seven ES, Leblanc RM. Crossing the blood-brain barrier with nanoparticles. J Control Release. 2018;270:290–303.

    Article  CAS  Google Scholar 

  8. Baker D, Gerritsen W, Rundle J, Amor S. Critical appraisal of animal models of multiple sclerosis. Mult Scler. 2011;17(6):647–57.

    Article  Google Scholar 

  9. Sloane E, Ledeboer A, Seibert W, Coats B, van Strien M, Maier SF, Johnson KW, Chavez R, Watkins LR, Leinwand L and others. Anti-inflammatory cytokine gene therapy decreases sensory and motor dysfunction in experimental Multiple Sclerosis: MOG-EAE behavioral and anatomical symptom treatment with cytokine gene therapy. Brain Behav. Immun. 2009;23(1):92–100.

    Article  CAS  Google Scholar 

  10. Male D, Gromnicova R, McQuaid C. Gold nanoparticles for imaging and drug transport to the CNS. Int Rev Neurobiol. 2016;130:155–98.

    Article  CAS  Google Scholar 

  11. Brodell DW, Jain A, Elfar JC, Mesfin A. National trends in the management of central cord syndrome: an analysis of 16,134 patients. Spine J. 2015;15(3):435–42.

    Article  Google Scholar 

  12. Cardoso AM, Guedes JR, Cardoso AL, Morais C, Cunha P, Viegas AT, Costa R, Jurado A, Pedroso de Lima MC. Recent trends in nanotechnology toward CNS diseases: lipid-based nanoparticles and exosomes for targeted therapeutic delivery. Int Rev Neurobiol. 2016;130:1–40.

    Article  CAS  Google Scholar 

  13. Patel T, Zhou J, Piepmeier JM, Saltzman WM. Polymeric nanoparticles for drug delivery to the central nervous system. Adv Drug Deliv Rev. 2012;64(7):701–5.

    Article  CAS  Google Scholar 

  14. Lecesne R, Drouillard J, Cisse R, Schiratti M. Contribution of Abdoscan in MRI cholangio-pancreatography and MRI urography. J Radiol. 1998;79(6):573–5.

    CAS  Google Scholar 

  15. Zong Y, Wu J, Shen K. Nanoparticle albumin-bound paclitaxel as neoadjuvant chemotherapy of breast cancer: a systematic review and meta-analysis. Oncotarget. 2017;8(10):17360–72.

    Article  Google Scholar 

  16. Olivier JC, Fenart L, Chauvet R, Pariat C, Cecchelli R, Couet W. Indirect evidence that drug brain targeting using polysorbate 80-coated polybutylcyanoacrylate nanoparticles is related to toxicity. Pharm Res. 1999;16(12):1836–42.

    Article  CAS  Google Scholar 

  17. Kreuter J, Alyautdin RN, Kharkevich DA, Ivanov AA. Passage of peptides through the blood-brain barrier with colloidal polymer particles (nanoparticles). Brain Res. 1995;674(1):171–4.

    Article  CAS  Google Scholar 

  18. Schroeder U, Sommerfeld P, Sabel BA. Efficacy of oral dalargin-loaded nanoparticle delivery across the blood-brain barrier. Peptides. 1998;19(4):777–80.

    Article  CAS  Google Scholar 

  19. Schroeder U, Schroeder H, Sabel BA. Body distribution of 3H-labelled dalargin bound to poly(butyl cyanoacrylate) nanoparticles after i.v. injections to mice. Life Sci. 2000;66(6):495–502.

    Article  CAS  Google Scholar 

  20. Koffie RM, Farrar CT, Saidi LJ, William CM, Hyman BT, Spires-Jones TL. Nanoparticles enhance brain delivery of blood-brain barrier-impermeable probes for in vivo optical and magnetic resonance imaging. PNAS. 2011;108(46):18837–42.

    Article  CAS  Google Scholar 

  21. Ramot Y, Haim-Zada M, Domb AJ, Nyska A. Biocompatibility and safety of PLA and its copolymers. Adv Drug Deliv Rev. 2016;107:153–62.

    Article  CAS  Google Scholar 

  22. Mahapatro A, Singh DK. Biodegradable nanoparticles are excellent vehicle for site directed in-vivo delivery of drugs and vaccines. J. Nanobiotechnology. 2011;9:55.

    Article  CAS  Google Scholar 

  23. Lu JM, Wang X, Marin-Muller C, Wang H, Lin PH, Yao Q, Chen C. Current advances in research and clinical applications of PLGA-based nanotechnology. Expert Rev. Mol. Diagn. 2009;9(4):325–41.

    Article  CAS  Google Scholar 

  24. Grabrucker AM, Garner CC, Boeckers TM, Bondioli L, Ruozi B, Forni F, Vandelli MA, Tosi G. Development of novel Zn2 + loaded nanoparticles designed for cell-type targeted drug release in CNS neurons: in vitro evidences. PLoS ONE. 2011;6(3):e17851.

    Article  CAS  Google Scholar 

  25. Mathew A, Fukuda T, Nagaoka Y, Hasumura T, Morimoto H, Yoshida Y, Maekawa T, Venugopal K, Kumar DS. Curcumin loaded-PLGA nanoparticles conjugated with Tet-1 peptide for potential use in Alzheimer’s disease. PLoS ONE. 2012;7(3):e32616.

    Article  CAS  Google Scholar 

  26. Lei C, Davoodi P, Zhan W, Kah-Hoe Chow P, Wang CH. Development of Nanoparticles for Drug Delivery to Brain Tumor: The Effect of Surface Materials on Penetration into Brain Tissue. Sci: J. Pharm; 2018.

    Google Scholar 

  27. Nabeshima T, Nitta A. Memory impairment and neuronal dysfunction induced by beta-amyloid protein in rats. Tohoku J Exp Med. 1994;174(3):241–9.

    Article  CAS  Google Scholar 

  28. Ringman JM, Frautschy SA, Cole GM, Masterman DL, Cummings JL. A potential role of the curry spice curcumin in Alzheimer’s disease. Curr Alzheimer Res. 2005;2(2):131–6.

    Article  CAS  Google Scholar 

  29. Mulik RS, Monkkonen J, Juvonen RO, Mahadik KR, Paradkar AR. ApoE3 mediated poly(butyl) cyanoacrylate nanoparticles containing curcumin: study of enhanced activity of curcumin against beta amyloid induced cytotoxicity using in vitro cell culture model. Mol Pharm. 2010;7(3):815–25.

    Article  CAS  Google Scholar 

  30. Doggui S, Sahni JK, Arseneault M, Dao L, Ramassamy C. Neuronal uptake and neuroprotective effect of curcumin-loaded PLGA nanoparticles on the human SK-N-SH cell line. J Alzheimers Dis. 2012;30(2):377–92.

    Article  CAS  Google Scholar 

  31. Cheng KK, Yeung CF, Ho SW, Chow SF, Chow AH, Baum L. Highly stabilized curcumin nanoparticles tested in an in vitro blood-brain barrier model and in Alzheimer’s disease Tg2576 mice. AAPS J. 2013;15(2):324–36.

    Article  CAS  Google Scholar 

  32. Mathur R, Ince PG, Minett T, Garwood CJ, Shaw PJ, Matthews FE, Brayne C, Simpson JE, Wharton SB. A reduced astrocyte response to beta-amyloid plaques in the ageing brain associates with cognitive impairment. PLoS ONE. 2015;10(2):e0118463.

    Article  CAS  Google Scholar 

  33. Zhou Y, Sharma S, Peng Z, Leblanc R. Polymers in Carbon Dots: A Review. Polymers. 2017;9(2):67.

    Article  CAS  Google Scholar 

  34. Li S, Peng Z, Leblanc RM. Method To Determine Protein Concentration in the Protein-Nanoparticle Conjugates Aqueous Solution Using Circular Dichroism Spectroscopy. Anal Chem. 2015;87(13):6455–9.

    Article  CAS  Google Scholar 

  35. Peng Z, Li S, Han X, Al-Youbi AO, Bashammakh AS, El-Shahawi MS, Leblanc RM. Determination of the composition, encapsulation efficiency and loading capacity in protein drug delivery systems using circular dichroism spectroscopy. Anal Chim Acta. 2016;937:113–8.

    Article  CAS  Google Scholar 

  36. Xu G, Mahajan S, Roy I, Yong KT. Theranostic quantum dots for crossing blood-brain barrier in vitro and providing therapy of HIV-associated encephalopathy. Front Pharmacol. 2013;4:140.

    Google Scholar 

  37. Zheng M, Ruan S, Liu S, Sun T, Qu D, Zhao H, Xie Z, Gao H, Jing X, Sun Z. Self-Targeting Fluorescent Carbon Dots for Diagnosis of Brain Cancer Cells. ACS Nano. 2015;9(11):11455–61.

    Article  CAS  Google Scholar 

  38. Li S, Amat D, Peng Z, Vanni S, Raskin S, De Angulo G, Othman AM, Graham RM, Leblanc RM. Transferrin conjugated nontoxic carbon dots for doxorubicin delivery to target pediatric brain tumor cells. Nanoscale. 2016;8(37):16662–9.

    Article  CAS  Google Scholar 

  39. Liu Y, Lu W. Recent advances in brain tumor-targeted nano-drug delivery systems. Expert Opin Drug Deliv. 2012;9(6):671–86.

    Article  CAS  Google Scholar 

  40. Luciani A, Olivier JC, Clement O, Siauve N, Brillet PY, Bessoud B, Gazeau F, Uchegbu IF, Kahn E, Frija G and others. Glucose-receptor MR imaging of tumors: study in mice with PEGylated paramagnetic niosomes. Radiology 2004;231(1):135–42.

    Article  Google Scholar 

  41. DeMarino C, Schwab A, Pleet M, Mathiesen A, Friedman J, El-Hage N, Kashanchi F. Biodegradable Nanoparticles for Delivery of Therapeutics in CNS Infection. J. Neuroimmune Pharmacol. 2017;12(1):31–50.

    Article  Google Scholar 

  42. Helm F, Fricker G. Liposomal conjugates for drug delivery to the central nervous system. Pharmaceutics. 2015;7(2):27–42.

    Article  CAS  Google Scholar 

  43. Pardridge WM. Molecular Trojan horses for blood-brain barrier drug delivery. Curr Opin Pharmacol. 2006;6(5):494–500.

    Article  CAS  Google Scholar 

  44. McConnell EM, Ventura K, Dwyer Z, Hunt V, Koudrina A, Holahan MR, DeRosa MC. In Vivo Use of a Multi-DNA Aptamer-Based Payload/Targeting System To Study Dopamine Dysregulation in the Central Nervous System. Neurosci: ACS Chem; 2018.

    Google Scholar 

  45. Jin SX, Bi DZ, Wang J, Wang YZ, Hu HG, Deng YH. Pharmacokinetics and tissue distribution of zidovudine in rats following intravenous administration of zidovudine myristate loaded liposomes. Pharmazie. 2005;60(11):840–3.

    CAS  Google Scholar 

  46. Laquintana V, Trapani A, Denora N, Wang F, Gallo JM, Trapani G. New strategies to deliver anticancer drugs to brain tumors. Expert Opin Drug Deliv. 2009;6(10):1017–32.

    Article  CAS  Google Scholar 

  47. Salvati E, Re F, Sesana S, Cambianica I, Sancini G, Masserini M, Gregori M. Liposomes functionalized to overcome the blood-brain barrier and to target amyloid-beta peptide: the chemical design affects the permeability across an in vitro model. Int. J. Nanomedicine. 2013;8:1749–58.

    Google Scholar 

  48. Rueda Dominguez A, Olmos Hidalgo D, Viciana Garrido R, Torres Sanchez E. Liposomal cytarabine (DepoCyte) for the treatment of neoplastic meningitis. Clin Transl Oncol. 2005;7(6):232–8.

    Article  Google Scholar 

  49. Khatri P. Evaluation and management of acute ischemic stroke. Continuum (Minneap Minn) 2014;20(2 Cerebrovascular Disease):283–95.

    Google Scholar 

  50. Kim H, Britton GL, Peng T, Holland CK, McPherson DD, Huang SL. Nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage. Int. J. Nanomedicine. 2014;9:155–65.

    Google Scholar 

  51. Hwang H, Jeong HS, Oh PS, Na KS, Kwon J, Kim J, Lim S, Sohn MH, Jeong HJ. Improving Cerebral Blood Flow Through Liposomal Delivery of Angiogenic Peptides: Potential of (1)(8)F-FDG PET Imaging in Ischemic Stroke Treatment. J Nucl Med. 2015;56(7):1106–11.

    Article  CAS  Google Scholar 

  52. Bernard ED, Beking MA, Rajamanickam K, Tsai EC, Derosa MC. Target binding improves relaxivity in aptamer-gadolinium conjugates. J Biol Inorg Chem. 2012;17(8):1159–75.

    Article  CAS  Google Scholar 

  53. Du Y, Qin Y, Li Z, Yang X, Zhang J, Westwick H, Tsai E, Cao X. Development of multifunctional nanoparticles towards applications in non-invasive magnetic resonance imaging and axonal tracing. J Biol Inorg Chem. 2017;22(8):1305–16.

    Article  CAS  Google Scholar 

  54. Hainfeld JF, Smilowitz HM, O’Connor MJ, Dilmanian FA, Slatkin DN. Gold nanoparticle imaging and radiotherapy of brain tumors in mice. Nanomedicine (Lond). 2013;8(10):1601–9.

    Article  CAS  Google Scholar 

  55. Gibson JD, Khanal BP, Zubarev ER. Paclitaxel-functionalized gold nanoparticles. J Am Chem Soc. 2007;129(37):11653–61.

    Article  CAS  Google Scholar 

  56. Kim B, Han G, Toley BJ, Kim C-k, Rotello VM, Forbes NS. Tuning payload delivery in tumour cylindroids using gold nanoparticles. Nat. Nanotechnol. 2010;5:465.

    Article  CAS  Google Scholar 

  57. Zhang Y, Walker JB, Minic Z, Liu F, Goshgarian H, Mao G. Transporter protein and drug-conjugated gold nanoparticles capable of bypassing the blood-brain barrier. Sci. Rep. 2016;6:25794.

    Article  CAS  Google Scholar 

  58. de Robles P, Fiest KM, Frolkis AD, Pringsheim T, Atta C, St. Germaine-Smith C, Day L, Lam D, Jette N. The worldwide incidence and prevalence of primary brain tumors: a systematic review and meta-analysis. Neuro-Oncology 2015;17(6):776–783.

    Google Scholar 

  59. Lara-Velazquez M, Al-Kharboosh R, Jeanneret S, Vazquez-Ramos C, Mahato D, Tavanaiepour D, Rahmathulla G, Quinones-Hinojosa A. Advances in Brain Tumor Surgery for Glioblastoma in Adults. Brain Sci. 2017;7(12):166.

    Article  CAS  Google Scholar 

  60. Joh DY, Sun L, Stangl M, Al Zaki A, Murty S, Santoiemma PP, Davis JJ, Baumann BC, Alonso-Basanta M, Bhang D and others. Selective targeting of brain tumors with gold nanoparticle-induced radiosensitization. PLoS One 2013;8(4):e62425.

    Article  CAS  Google Scholar 

  61. Shilo M, Motiei M, Hana P, Popovtzer R. Transport of nanoparticles through the blood–brain barrier for imaging and therapeutic applications. Nanoscale. 2014;6(4):2146–52.

    Article  CAS  Google Scholar 

  62. Trickler WJ, Lantz SM, Murdock RC, Schrand AM, Robinson BL, Newport GD, Schlager JJ, Oldenburg SJ, Paule MG, Slikker JW and others. Silver Nanoparticle Induced Blood-Brain Barrier Inflammation and Increased Permeability in Primary Rat Brain Microvessel Endothelial Cells. Toxicol Sci. 2010;118(1):160–170.

    Article  CAS  Google Scholar 

  63. Ajetunmobi A, Prina-Mello A, Volkov Y, Corvin A, Tropea D. Nanotechnologies for the study of the central nervous system. Prog Neurobiol. 2014;123:18–36.

    Article  CAS  Google Scholar 

  64. Provenzale JM, Silva GA. Uses of nanoparticles for central nervous system imaging and therapy. AJNR Am J Neuroradiol. 2009;30(7):1293–301.

    Article  CAS  Google Scholar 

  65. Neuwelt EA, Varallyay CG, Manninger S, Solymosi D, Haluska M, Hunt MA, Nesbit G, Stevens A, Jerosch-Herold M, Jacobs PM and others. The potential of ferumoxytol nanoparticle magnetic resonance imaging, perfusion, and angiography in central nervous system malignancy: a pilot study. Neurosurgery 2007;60(4):601–11; discussion 611-2.

    Article  Google Scholar 

  66. Neuwelt EA, Varallyay P, Bago AG, Muldoon LL, Nesbit G, Nixon R. Imaging of iron oxide nanoparticles by MR and light microscopy in patients with malignant brain tumours. Neuropathol Appl Neurobiol. 2004;30(5):456–71.

    Article  CAS  Google Scholar 

  67. Jiang W, Xie H, Ghoorah D, Shang Y, Shi H, Liu F, Yang X, Xu H. Conjugation of functionalized SPIONs with transferrin for targeting and imaging brain glial tumors in rat model. PLoS ONE. 2012;7(5):e37376.

    Article  CAS  Google Scholar 

  68. Hu Y, Hu H, Yan J, Zhang C, Li Y, Wang M, Tan W, Liu J, Pan Y. Multifunctional Porous Iron Oxide Nanoagents for MRI and Photothermal/Chemo Synergistic Therapy. Bioconjug Chem. 2018;29(4):1283–90.

    Article  CAS  Google Scholar 

  69. Pardridge WM. The blood-brain barrier: Bottleneck in brain drug development. NeuroRX. 2005;2(1):3–14.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Ottawa Hospital Research Institute, Loeb Building, 725 Parkdale Ave, Ottawa, ON, K1Y 4E9, Canada

    Suzan Chen, Angela Auriat & Eve C. Tsai

  2. Department of Chemistry and Institute of Biochemistry, Carleton University, 225 Steacie Building 1125 Colonel by Drive, Ottawa, ON, K1S 5B6, Canada

    Anna Koudrina & Maria DeRosa

  3. Faculty of Engineering, University of Ottawa, Colonel by Hall 161 Louis Pasteur Private, Room CBY A-337, Ottawa, ON, K1N 6N5, Canada

    Xudong Cao

  4. Division of Neurosurgery, Suruchi Bhargava Chair in Spinal Cord and Brain Regeneration Research, University of Ottawa, The Ottawa Hospital—Civic Campus C2, 1053 Carling Ave, Ottawa, ON, K1Y 4E9, Canada

    Eve C. Tsai

Authors
  1. Suzan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Angela Auriat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anna Koudrina
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria DeRosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xudong Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eve C. Tsai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eve C. Tsai .

Editor information

Editors and Affiliations

  1. Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, ON, Canada

    Emilio I. Alarcon

  2. Center for Applied Nanotechnology, Universidad Mayor, Santiago, RM, Chile

    Manuel Ahumada

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Chen, S., Auriat, A., Koudrina, A., DeRosa, M., Cao, X., Tsai, E.C. (2019). Nano-engineering Nanoparticles for Clinical Use in the Central Nervous System: Clinically Applicable Nanoparticles and Their Potential Uses in the Diagnosis and Treatment of CNS Aliments. In: Alarcon, E., Ahumada, M. (eds) Nanoengineering Materials for Biomedical Uses. Springer, Cham. https://doi.org/10.1007/978-3-030-31261-9_7

Download citation

Publish with us

Policies and ethics

Search

Navigation