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Brain-Penetrating Nanoparticles for Analysis of the Brain Microenvironment

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Biomedical Nanotechnology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1570))

Abstract

The past decade has witnessed explosive growth in the development of nanoparticle-based therapies for the treatment of neurological disorders and diseases. The systemic delivery of therapeutic carriers to the central nervous system (CNS) is hindered by both the blood–brain barrier (BBB) and the porous and electrostatically charged brain extracellular matrix (ECM), which acts as a steric and adhesive barrier. Therapeutic delivery to the brain is influenced by changes in the brain microenvironment, which can occur as a function of physiology, biology, pathology, and developmental age. Brain-penetrating nanoparticles (BPNs) are an optimal platform not only for therapeutic delivery to the brain, but also for evaluating changes in the brain microenvironment. BPNs possess both the capability to readily move within their local environment to survey their surroundings and the ability to reach the diffuse disease cells often associated with CNS disorders. To achieve effective delivery of BPNs to specific locations within the brain requires careful control over the nanoparticle’s transport properties. Here, we describe the process of conjugating a dense layer of poly(ethylene glycol) (PEG) to the surface of nonbiodegradable nanoparticles to achieve brain-penetrating capabilities.

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References

  1. Patel T, Zhou J, Piepmeier JM, Saltzman WM (2012) Polymeric nanoparticles for drug delivery to the central nervous system. Adv Drug Deliv Rev 64(7):701–705. doi:10.1016/j.addr.2011.12.006

    Article  CAS  Google Scholar 

  2. Nance EA, Woodworth GF, Sailor KA, Shih TY, Xu Q, Swaminathan G, Xiang D, Eberhart C, Hanes J (2012) A dense poly(ethylene glycol) coating improves penetration of large polymeric nanoparticles within brain tissue. Sci Transl Med 4(149):149ra119. doi:10.1126/scitranslmed.3003594

    Article  Google Scholar 

  3. Nance E, Timbie K, Miller GW, Song J, Louttit C, Klibanov AL, Shih TY, Swaminathan G, Tamargo RJ, Woodworth GF, Hanes J, Price RJ (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. doi:10.1016/j.jconrel.2014.06.031

    Article  CAS  Google Scholar 

  4. Strohbehn G, Coman D, Han L, Ragheb RR, Fahmy TM, Huttner AJ, Hyder F, Piepmeier JM, Saltzman WM, Zhou J (2015) Imaging the delivery of brain-penetrating PLGA nanoparticles in the brain using magnetic resonance. J Neurooncol 121(3):441–449. doi:10.1007/s11060-014-1658-0

    Article  CAS  Google Scholar 

  5. Nance E, Zhang C, Shih TY, Xu Q, Schuster BS, Hanes J (2014) Brain-penetrating nanoparticles improve paclitaxel efficacy in malignant glioma following local administration. ACS Nano 8(10):10655–10664. doi:10.1021/nn504210g

    Article  CAS  Google Scholar 

  6. Mead BP, Mastorakos P, Suk JS, Klibanov AL, Hanes J, Price RJ (2016) Targeted gene transfer to the brain via the delivery of brain-penetrating DNA nanoparticles with focused ultrasound. J Control Release 223:109–117. doi:10.1016/j.jconrel.2015.12.034

    Article  CAS  Google Scholar 

  7. Burke CW, Suk JS, Kim AJ, Hsiang YH, Klibanov AL, Hanes J, Price RJ (2012) Markedly enhanced skeletal muscle transfection achieved by the ultrasound-targeted delivery of non-viral gene nanocarriers with microbubbles. J Control Release 162(2):414–421. doi:10.1016/j.jconrel.2012.07.005

    Article  CAS  Google Scholar 

  8. Wohlfart S, Gelperina S, Kreuter J (2012) Transport of drugs across the blood-brain barrier by nanoparticles. J Control Release 161(2):264–273. doi:10.1016/j.jconrel.2011.08.017

    Article  CAS  Google Scholar 

  9. Kreuter J (2014) Drug delivery to the central nervous system by polymeric nanoparticles: what do we know? Adv Drug Deliv Rev 71:2–14. doi:10.1016/j.addr.2013.08.008

    Article  CAS  Google Scholar 

  10. Zhou J, Patel TR, Sirianni RW, Strohbehn G, Zheng MQ, Duong N, Schafbauer T, Huttner AJ, Huang Y, Carson RE, Zhang Y, Sullivan DJ Jr, Piepmeier JM, Saltzman WM (2013) Highly penetrative, drug-loaded nanocarriers improve treatment of glioblastoma. Proc Natl Acad Sci USA 110(29):11751–11756. doi:10.1073/pnas.1304504110

    Article  CAS  Google Scholar 

  11. Yang M, Lai SK, Wang YY, Zhong W, Happe C, Zhang M, Fu J, Hanes J (2011) Biodegradable nanoparticles composed entirely of safe materials that rapidly penetrate human mucus. Angew Chem Int Ed Engl 50(11):2597–2600. doi:10.1002/anie.201006849

    Article  CAS  Google Scholar 

  12. Tang BC, Dawson M, Lai SK, Wang YY, Suk JS, Yang M, Zeitlin P, Boyle MP, Fu J, Hanes J (2009) Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier. Proc Natl Acad Sci USA 106(46):19268–19273. doi:10.1073/pnas.0905998106

    Article  CAS  Google Scholar 

  13. Nance E, Porambo M, Zhang F, Mishra MK, Buelow M, Getzenberg R, Johnston M, Kannan RM, Fatemi A, Kannan S (2015) Systemic dendrimer-drug treatment of ischemia-induced neonatal white matter injury. J Control Release 214:112–120. doi:10.1016/j.jconrel.2015.07.009

    Article  CAS  Google Scholar 

  14. Kannan S, Dai H, Navath RS, Balakrishnan B, Jyoti A, Janisse J, Romero R, Kannan RM (2012) Dendrimer-based postnatal therapy for neuroinflammation and cerebral palsy in a rabbit model. Sci Transl Med 4(130):130ra146. doi:10.1126/scitranslmed.3003162

    Article  Google Scholar 

  15. Jenkins SI, Weinberg D, Al-Shakli AF, Fernandes AR, Yiu HH, Telling ND, Roach P, Chari DM (2016) ‘Stealth’ nanoparticles evade neural immune cells but also evade major brain cell populations: implications for PEG-based neurotherapeutics. J Control Release 224:136–145. doi:10.1016/j.jconrel.2016.01.013

    Article  CAS  Google Scholar 

  16. Suk JS, Xu Q, Kim N, Hanes J, Ensign LM (2015) PEGylation as a strategy for improving nanoparticle-based drug and gene delivery, Adv Drug Deliv Rev. doi:10.1016/j.addr.2015.09.012

  17. Popielarski SR, Pun SH, Davis ME (2005) A nanoparticle-based model delivery system to guide the rational design of gene delivery to the liver. 1. Synthesis and characterization. Bioconjug Chem 16(5):1063–1070. doi:10.1021/bc050113d

    Article  CAS  Google Scholar 

  18. Wang YY, Lai SK, Suk JS, Pace A, Cone R, Hanes J (2008) Addressing the PEG mucoadhesivity paradox to engineer nanoparticles that “slip” through the human mucus barrier. Angew Chem Int Ed Engl 47(50):9726–9729. doi:10.1002/anie.200803526

    Article  CAS  Google Scholar 

  19. Perry JL, Reuter KG, Kai MP, Herlihy KP, Jones SW, Luft JC, Napier M, Bear JE, DeSimone JM (2012) PEGylated PRINT nanoparticles: the impact of PEG density on protein binding, macrophage association, biodistribution, and pharmacokinetics. Nano Lett 12(10):5304–5310. doi:10.1021/nl302638g

    Article  CAS  Google Scholar 

  20. Pombo Garcia K, Zarschler K, Barbaro L, Barreto JA, O’Malley W, Spiccia L, Stephan H, Graham B (2014) Zwitterionic-coated “stealth” nanoparticles for biomedical applications: recent advances in countering biomolecular corona formation and uptake by the mononuclear phagocyte system. Small 10(13):2516–2529. doi:10.1002/smll.201303540

    Article  Google Scholar 

  21. Amoozgar Z, Yeo Y (2012) Recent advances in stealth coating of nanoparticle drug delivery systems. Wiley Interdiscip Rev Nanomed Nanobiotechnol 4(2):219–233. doi:10.1002/wnan.1157

    Article  CAS  Google Scholar 

  22. Yang Q, Lai SK (2015) Anti-PEG immunity: emergence, characteristics, and unaddressed questions. Wiley Interdiscip Rev Nanomed Nanobiotechnol 7(5):655–677. doi:10.1002/wnan.1339

    Article  Google Scholar 

  23. Rizzo V, Pinciroli V (2005) Quantitative NMR in synthetic and combinatorial chemistry. J Pharm Biomed Anal 38(5):851–857. doi:10.1016/j.jpba.2005.01.045

    Article  CAS  Google Scholar 

  24. Suk JS, Xu Q, Kim N, Hanes J, Ensign LM (2016) PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv Drug Deliv Rev 99(Pt A):28–51. doi:10.1016/j.addr.2015.09.012

    Article  CAS  Google Scholar 

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Acknowledgements

The author would like to acknowledge J. Hanes and the Center for Nanomedicine at Johns Hopkins University.

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Authors and Affiliations

  1. Department of Chemical Engineering, University of Washington, 105 Benson Hall, Box 351750, Seattle, WA, 98195, USA

    Elizabeth Nance

Authors
  1. Elizabeth Nance
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Correspondence to Elizabeth Nance .

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Editors and Affiliations

  1. Department of Chemistry and International Institute for Nanotechnology, Northwestern University, Evanston, Illinois, USA

    Sarah Hurst Petrosko

  2. Department of Biomedical Engineering, University of Delaware, Newark, Delaware, USA

    Emily S. Day

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Nance, E. (2017). Brain-Penetrating Nanoparticles for Analysis of the Brain Microenvironment. In: Petrosko, S., Day, E. (eds) Biomedical Nanotechnology. Methods in Molecular Biology, vol 1570. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6840-4_6

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  • DOI: https://doi.org/10.1007/978-1-4939-6840-4_6

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6838-1

  • Online ISBN: 978-1-4939-6840-4

  • eBook Packages: Springer Protocols

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