Skip to main content

Upconversion Nanoparticle-Based Strategy for Crossing the Blood-Brain Barrier to Treat the Central Nervous System Disease

  • Protocol
  • First Online:
Theranostics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2054))

Abstract

The blood-brain barrier (BBB) is a major challenge for the treatment of central nervous system (CNS) diseases. The BBB strictly regulates the movement of molecules into and out of the brain, and therefore protects the brain from noxious agents. However, for this reason the BBB also acts as a major obstacle that prevents most therapeutic molecules from getting into the target site of the brain. Therefore, it is essential to develop an efficient and general approach to overcome the BBB and transport the drug to the targeted region. Nanoparticle-based drug delivery systems are emerging as a promising drug delivery platform, due to their distinct advantages of tunable biophysical properties such as surface chemistry, size, and shape leading to various biological actions (like clearance, biodistribution, and biocompatibility) in the body. Therefore, it was hypothesized that the surface and shape of nanoparticles will influence their BBB permeation efficiency. Here, we describe a series of upconversion nanoparticles with different surfaces (oleic acid-free, DNA-modified, Silica coating, and PEG-encapsulated), PEGylated UCNPs with various shapes were generated (including sphere and rod). The cellular uptake ability, biodistribution, and BBB penetration of those UCNPs were assessed in cultured cells (NSC-34 neuron- like cells) and in vivo (zebrafish models).

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

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
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

References

  1. Petros RA, Desimone JM (2010) Strategies in the design of nanoparticles for therapeutic applications. Nat Rev Drug Discov 9:615–627

    Article  CAS  Google Scholar 

  2. Bogdan N, Vetrone F, Ozin GA, Capobianco JA (2011) Synthesis of ligand-free colloidally stable water dispersible brightly luminescent lanthanide-doped upconverting nanoparticles. Nano Lett 11:835–840

    Article  CAS  Google Scholar 

  3. Champion JA, Katare YK, Mitragotri S (2007) Particle shape: a new design parameter for micro- and nanoscale drug delivery carriers. J Control Release 121:3–9

    Article  CAS  Google Scholar 

  4. Chen C, Duan Z, Yuan Y, Li R, Pang L, Liang J, Xu X, Wang J (2017) Peptide-22 and cyclic RGD functionalized liposomes for glioma targeting drug delivery overcoming BBB and BBTB. ACS Appl Mater Interfaces 9:5864–5873

    Article  CAS  Google Scholar 

  5. Kim JH, Kim JH, Kim KW, Kim MH, Yu YS (2009) Intravenously administered gold nanoparticles pass through the blood-retinal barrier depending on the particle size, and induce no retinal toxicity. Nanotechnology 20:505101

    Article  Google Scholar 

  6. Cheng D, Shami GJ, Morsch M, Chung RS, Braet F (2016) Ultrastructural mapping of the zebrafish gastrointestinal system as a basis for experimental drug studies. Biomed Res Int 2016:1–13

    Google Scholar 

  7. Choi HS, Ipe BI, Misra P, Lee JH, Bawendi MG, Frangioni JV (2009) Tissue- and organ-selective biodistribution of NIR fluorescent quantum dots. Nano Lett 9:2354–2359

    Article  CAS  Google Scholar 

  8. Don EK, Formella I, Badrock AP, Hall TE, Morsch M, Hortle E, Hogan A, Chow S, Gwee SSL, Stoddart JJ, Nicholson G, Chung R, Cole NJ (2017) A Tol2 gateway-compatible toolbox for the study of the nervous system and neurodegenerative disease. Zebrafish 14:69–72

    Article  Google Scholar 

  9. Masserini M (2013) Nanoparticles for brain drug delivery. ISRN Biochem 2013:1–18

    Article  Google Scholar 

  10. Ge X, Dong L, Sun L, Song Z, Wei R, Shi L, Chen H (2015) New nanoplatforms based on UCNPs linking with polyhedral oligomeric silsesquioxane (POSS) for multimodal bioimaging. Nanoscale 7:7206–7215

    Article  CAS  Google Scholar 

  11. Gref R, Couvreur P, Barratt G, Mysiakine E (2003) Surface-engineered nanoparticles for multiple ligand coupling. Biomaterials 24:4529–4537

    Article  CAS  Google Scholar 

  12. Haase M, Schäfer H (2011) Upconverting nanoparticles. Angew Chem Int Ed 50:5808–5829

    Article  CAS  Google Scholar 

  13. Huang X, Teng X, Chen D, Tang F, He J (2010) The effect of the shape of mesoporous silica nanoparticles on cellular uptake and cell function. Biomaterials 31:438–448

    Article  CAS  Google Scholar 

  14. Jiang W, Kim BYS, Rutka JT, Chan WCW (2008) Nanoparticle-mediated cellular response is size-dependent. Nat Nanotechnol 9:615–627

    Google Scholar 

  15. Kuang Y, An S, Guo Y, Huang S, Shao K, Liu Y, Li J, Ma H, Jiang C (2013) T7 peptide-functionalized nanoparticles utilizing RNA interference for glioma dual targeting. Int J Pharm 454:11–20

    Article  CAS  Google Scholar 

  16. Kurakhmaeva KB, Djindjikhashvili IA, Petrov VE, Balabanyan VU, Voronina TA, Trofimov SS, Kreuter J, Gelperina S, Begley D, Alyautdin RN (2009) Brain targeting of nerve growth factor using poly(butyl cyanoacrylate) nanoparticles. J Drug Target 17:564–574

    Article  CAS  Google Scholar 

  17. Lin S, Li M, Dujardin E, Girard C, Mann S (2005) One-dimensional Plasmon coupling by facile self-assembly of gold nanoparticles into branched chain networks. Adv Mater 17:2553–2559

    Article  CAS  Google Scholar 

  18. Lin YS, Haynes CL (2010) Impacts of mesoporous silica nanoparticle size, pore ordering, and pore integrity on hemolytic activity. J Am Chem Soc 132:4834–4842

    Article  CAS  Google Scholar 

  19. Liu C, Gao Z, Zeng J, Hou Y, Fang F, Li Y, Qiao R, Shen L, Lei H, Yang W, Gao M (2013) Magnetic/upconversion fluorescent dual-modal molecular probes for imaging tiny tumors in vivo. ACS Nano 7:7227–7240

    Article  CAS  Google Scholar 

  20. Liu D, Xu X, Du Y, Qin X, Zhang Y, Ma C, Wen S, Ren W, Goldys EM, Piper JA, Dou S, Liu X, Jin D (2016) Three-dimensional controlled growth of monodisperse sub-50 nm heterogeneous nanocrystals. Nat Commun 7:10254

    Article  CAS  Google Scholar 

  21. Liu L, Venkatraman SS, Yang YY, Guo K, Lu J, He B, Moochhala S, Kan L (2008) Polymeric micelles anchored with TAT for delivery of antibiotics across the blood-brain barrier. Pept Sci 90:617–623

    Article  CAS  Google Scholar 

  22. Lu J, Chen Y, Liu D, Ren W, Lu Y, Shi Y, Piper J, Paulsen I, Jin D (2015) One-step protein conjugation to upconversion nanoparticles. Anal Chem 87:10406–10413

    Article  CAS  Google Scholar 

  23. Lu Y, Zhao J, Zhang R, Liu Y, Liu D, Goldys EM, Yang X, Xi P, Sunna A, Lu J, Shi Y, Leif RC, Huo Y, Shen J, Piper JA, Robinson JP, Jin D (2014) Tunable lifetime multiplexing using luminescent nanocrystals. Nat Photonics 8:32

    Article  CAS  Google Scholar 

  24. Mistry A, Stolnik S, Illum L (2009) Nanoparticles for direct nose-to-brain delivery of drugs. Int J Pharm 379:146–157

    Article  CAS  Google Scholar 

  25. Morsch M, Radford R, Lee A, Don EK, Badrock AP, Hall TE, Cole NJ, Chung R (2015) In vivo characterization of microglial engulfment of dying neurons in the zebrafish spinal cord. Front Cell Neurosci 9:321

    Article  Google Scholar 

  26. Park J, Mattessich T, Jay SM, Agawu A, Saltzman WM, Fahmy TM (2011) Enhancement of surface ligand display on PLGA nanoparticles with amphiphilic ligand conjugates. J Control Release 56:109–115

    Google Scholar 

  27. Shi B, Zhang H, Qiao SZ, Bi J, Dai S (2014) Intracellular microenvironment-responsive label-free autofluorescent nanogels for traceable gene delivery. Adv Healthc Mater 3:1839–1848

    Article  CAS  Google Scholar 

  28. Shi Y, Shi B, Dass AVE, Lu Y, Sayyadi N, Kautto L, Willows RD, Chung R, Piper J, Nevalainen H, Walsh B, Jin D, Packer NH (2016) Stable upconversion nanohybrid particles for specific prostate cancer cell immunodetection. Sci Rep 8:1–11

    CAS  Google Scholar 

  29. Singh SR, Grossniklaus HE, Kang SJ, Edelhauser HF, Ambati BK, Kompella UB (2009) Intravenous transferrin, RGD peptide and dual-targeted nanoparticles enhance anti-VEGF intraceptor gene delivery to laser-induced CNV. Gene Ther 16:645–659

    Article  CAS  Google Scholar 

  30. Sun W, Xie C, Wang H, Hu Y (2004) Specific role of polysorbate 80 coating on the targeting of nanoparticles to the brain. Biomaterials 25:3065–3071

    Article  CAS  Google Scholar 

  31. Tang J, Kemp KW, Hoogland S, Jeong KS, Liu H, Levina L, Furukawa M, Wang X, Debnath R, Cha D, Chou KW, Fischer A, Amassian A, Asbury JB, Sargent EH (2011) Colloidal-quantum-dot photovoltaics using atomic-ligand passivation. Nat Mater 10:765–771

    Article  CAS  Google Scholar 

  32. Wang F, Deng R, Liu X (2014) Preparation of core-shell NaGdF4 nanoparticles doped with luminescent lanthanide ions to be used as upconversion-based probes. Nat Protoc 9:1634–1644

    Article  CAS  Google Scholar 

  33. Wang F, Liu X (2009) Recent advances in the chemistry of lanthanide-doped upconversion nanocrystals. Chem Soc Rev 38:976–989

    Article  CAS  Google Scholar 

  34. Wang H, Zhang S, Liao Z, Wang C, Liu Y, Feng S, Jiang X, Chang J (2010) PEGlated magnetic polymeric liposome anchored with TAT for delivery of drugs across the blood-spinal cord barrier. Biomaterials 31:6589–6596

    Article  CAS  Google Scholar 

  35. Wong AC, Wright DW (2016) Size-dependent cellular uptake of DNA functionalized gold nanoparticles. Small 12:5592–5600

    Article  CAS  Google Scholar 

  36. Yi DK, Selvan ST, Lee SS, Papaefthymiou GC, Kundaliya D, Ying JY (2005) Silica-coated nanocomposites of magnetic nanoparticles and quantum dots. J Am Chem Soc 127:4990–4991

    Article  CAS  Google Scholar 

  37. Fu LB, Shi BY, Jin DY, Chung R (2017) A versatile upconversion surface evaluation platform for bio–nano surface selection for the nervous system. Nanoscale 9:13683–13692

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This project has been supported by NHMRC grants awarded to R.C. (APP1095215) and B.S. (APP1111611).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bingyang Shi .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Fu, L., Chung, R., Shi, B. (2019). Upconversion Nanoparticle-Based Strategy for Crossing the Blood-Brain Barrier to Treat the Central Nervous System Disease. In: Batra, J., Srinivasan, S. (eds) Theranostics. Methods in Molecular Biology, vol 2054. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9769-5_17

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-9769-5_17

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9768-8

  • Online ISBN: 978-1-4939-9769-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics