Skip to main content
SpringerLink
Log in

CD44 Targeted Lipid Nanoparticles for MicroRNA Therapy

  • Protocol
  • First Online:
Targeted Drug Delivery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1831))

Abstract

MicroRNAs are small noncoding RNAs that function as powerful endogenous regulators of gene expression. Dysregulation of MicroRNA biogenesis has been correlated with the onset and progression of many human diseases. MicroRNA therapy involves the re-equilibration of aberrant intracellular MicroRNA expression profiles for long-term disease management. Despite the significant potential of MicroRNA therapy, the utilization of MicroRNA-based therapeutics has been drastically hindered in practice by the lack of a targeted and translatable delivery vehicle. CD44 is a cell surface glycoprotein that facilitates cellular communication and motility through cell-cell and cell-extracellular matrix interactions. CD44 has been shown to be elevated in multiple disease states including cancer making it a potential diagnostic biomarker and an ideal receptor for targeted drug delivery systems. We describe a method for targeting CD44 using a lipid nanocarrier for the cytoplasmic delivery of active MicroRNA.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
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. Liu Z, Sall A, Yang D (2008) MicroRNA: an emerging therapeutic target and intervention tool. Int J Mol Sci 9(6):978–999. https://doi.org/10.3390/ijms9060978

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Cho WC (2010) MicroRNAs: potential biomarkers for cancer diagnosis, prognosis and targets for therapy. Int J Biochem Cell Biol 42(8):1273–1281. https://doi.org/10.1016/j.biocel.2009.12.014

    Article  PubMed  CAS  Google Scholar 

  3. Jonas S, Izaurralde E (2015) Towards a molecular understanding of microRNA-mediated gene silencing. Nat Rev Genet 16:421–433. https://doi.org/10.1038/nrg3965

    Article  PubMed  CAS  Google Scholar 

  4. Ha M, Kim VN (2014) Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol 15(8):509–524. https://doi.org/10.1038/nrm3838

    Article  PubMed  CAS  Google Scholar 

  5. Sassen S, Miska EA, Caldas C (2008) MicroRNA: implications for cancer. Virchows Arch 452(1):1–10. https://doi.org/10.1007/s00428-007-0532-2

    Article  PubMed  CAS  Google Scholar 

  6. Wiemer EAC (2007) The role of microRNAs in cancer: no small matter. Eur J Cancer 43(10):1529–1544. https://doi.org/10.1016/j.ejca.2007.04.002

    Article  PubMed  CAS  Google Scholar 

  7. Mishra PK, Tyagi N, Kumar M et al (2009) MicroRNAs as a therapeutic target for cardiovascular diseases. J Cell Mol Med 13(4):778–789. https://doi.org/10.1111/j.1582-4934.2009.00744.x

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Urbich C, Kuehbacher A, Dimmeler S (2008) Role of microRNAs in vascular diseases, inflammation, and angiogenesis. Cardiovasc Res 79(4):581–588. https://doi.org/10.1093/cvr/cvn156

    Article  PubMed  CAS  Google Scholar 

  9. Szabo G, Bala S (2013) MicroRNAs in liver disease. Nat Rev Gastroenterol Hepatol 10(9):542–552. https://doi.org/10.1038/nrgastro.2013.87

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Scaria V, Hariharan M, Brahmachari SK et al (2007) microRNA: an emerging therapeutic. ChemMedChem 2(6):789–792. https://doi.org/10.1002/cmdc.200600278

    Article  PubMed  CAS  Google Scholar 

  11. Nana-Sinkam SP, Croce CM (2013) Clinical applications for microRNAs in cancer. Clin Pharmacol Ther 93(1):98–104. https://doi.org/10.1038/clpt.2012.192

    Article  PubMed  CAS  Google Scholar 

  12. Muthiah M, Park I-K, Cho CS (2013) Nanoparticle mediated delivery of therapeutic genes- focus on miRNA therapeutics. Expert Opin Drug Deliv 10(9):1259–1273

    Article  CAS  PubMed  Google Scholar 

  13. Zhang Y, Wang Z, Gemeinhart RA (2013) Progress in microRNA delivery. J Control Release 172(3):962–974. https://doi.org/10.1016/j.jconrel.2013.09.015

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Torchilin VP (2010) Passive and active drug targeting: drug delivery to tumors as an example. In: Drug delivery. Springer, Berlin, pp 3–53

    Chapter  Google Scholar 

  15. Negi LM, Talegaonkar S, Jaggi M et al (2012) Role of CD44 in tumour progression and strategies for targeting. J Drug Target 20(7):561–573

    Article  CAS  PubMed  Google Scholar 

  16. Eliaz RE, Szoka FC (2001) Liposome-encapsulated doxorubicin targeted to CD44 a strategy to kill CD44-overexpressing tumor cells. Cancer Res 61(6):2592–2601

    PubMed  CAS  Google Scholar 

  17. Peer D, Margalit R (2004) Loading mitomycin C inside long circulating hyaluronan targeted nano-liposomes increases its antitumor activity in three mice tumor models. Int J Cancer 108(5):780–789. https://doi.org/10.1002/ijc.11615

    Article  PubMed  CAS  Google Scholar 

  18. Peer D, Park EJ, Morishita Y et al (2008) Systemic leukocyte-directed siRNA delivery revealing cyclin D1 as an anti-inflammatory target. Science 319(5863):627–630. https://doi.org/10.1126/science.1149859

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Hayward SL, Francis DM, Sis MJ et al (2015) Ionic driven embedment of hyaluronic acid coated liposomes in polyelectrolyte multilayer films for local therapeutic delivery. Sci Rep. https://doi.org/10.1038/srep14683

  20. Hayward SL, Francis DM, Kholmatov P et al (2016) Targeted delivery of MicroRNA-125a-5p by engineered lipid nanoparticles for the treatment of HER2 positive metastatic breast Cancer. J Biomed Nanotechnol. https://doi.org/10.1166/jbn.2016.2194

  21. Hayward SL, Wilson CL, Kidambi S (2016) Hyaluronic acid-conjugated liposome nanoparticles for targeted delivery to CD44 overexpressing glioblastoma cells. Oncotarget 7(23):34158–34171. https://doi.org/10.18632/oncotarget.8926

    Article  PubMed  PubMed Central  Google Scholar 

  22. Band V, Zajchowski D, Swisshelm K et al (1990) Tumor progression in four mammary epithelial cell lines derived from the same patient. Cancer Res 50(22):7351–7357

    PubMed  CAS  Google Scholar 

  23. Bangham A, Hill M, Miller N (1974) Preparation and use of liposomes as models of biological membranes. In: Methods in membrane biology, vol 1. Springer, Boston, pp 1–68. https://doi.org/10.1007/978-1-4615-7422-4_1

    Chapter  Google Scholar 

  24. Gregoriadis G (ed) (1988) Liposomes as drug carriers: recent trends and progress. John Wiley and Sons, Chichester

    Google Scholar 

  25. Mozafari M (2005) Liposomes an overview of manufacturing techniques. Cell Mol Biol Lett 10:711–719

    PubMed  CAS  Google Scholar 

  26. Akbarzadeh A, Rezaei-Sadabady R, Davaran S et al (2013) Liposome: classification, preparation, and applications. Nanoscale Res Lett 8(1):102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Mahmood T, Yang P-C (2012) Western blot: technique, theory, and trouble shooting. N Am J Med Sci 4(9):429–434. https://doi.org/10.4103/1947-2714.100998

    Article  PubMed  PubMed Central  Google Scholar 

  28. Hirano S (2012) Western blot analysis. Meth Mol Biol (Clifton, NJ) 926:87–97. https://doi.org/10.1007/978-1-62703-002-1_6

    Article  CAS  Google Scholar 

  29. Engel RH, Kaklamani VG (2007) HER2-positive breast cancer: current and future treatment strategies. Drugs 67(9):1329–1341

    Article  CAS  PubMed  Google Scholar 

  30. Scott GK, Goga A, Bhaumik D et al (2007) Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. J Biol Chem 282(2):1479–1486. https://doi.org/10.1074/jbc.M609383200

    Article  PubMed  CAS  Google Scholar 

  31. Rapley R, Manning DL (1998) RNA isolation and characterization protocols, vol 86. Humana Press, New York

    Book  Google Scholar 

  32. Landesman-Milo D, Goldsmith M, Leviatan Ben-Arye S et al (2013) Hyaluronan grafted lipid-based nanoparticles as RNAi carriers for cancer cells. Cancer Lett 334(2):221–227. https://doi.org/10.1016/j.canlet.2012.08.024

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. Vimla Band (University of Nebraska Medical Center) for kindly providing the 21MT-1 cells. We also thank Dr. Yusong Li for being able to use their labs DLS and Zeta potential machine. Lastly, we want to thank the UNL microscopy core facility for their assistance with confocal microscopy. This work was supported, in whole or in part, by P20 GM104320 (to the Nebraska Center for the Prevention of Obesity Diseases Pilot Grant to S.K.) and P20 GM113126 (to the Nebraska Center for Integrated Biomolecular Communication-Project Leader S.K.); UNL Office of Research and Development Biomedical Seed Grant (to S.K.); start up funds from University of Nebraska-Lincoln, Layman’s Award, MRSEC Seed Grant, and UNL Interdisciplinary Award.

Author information

Authors and Affiliations

  1. Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, Lincoln, NE, USA

    Stephen L. Hayward & Srivatsan Kidambi

  2. Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA

    Stephen L. Hayward

  3. Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA

    Srivatsan Kidambi

  4. Nebraska Center for Integrated Biomolecular Communication, University of Nebraska, Lincoln, NE, USA

    Srivatsan Kidambi

  5. Nebraska Center for the Prevention of Obesity Diseases, University of Nebraska, Lincoln, NE, USA

    Srivatsan Kidambi

  6. Nebraska Center for Materials and Nanoscience, University of Nebraska, Lincoln, NE, USA

    Srivatsan Kidambi

  7. Mary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE, USA

    Srivatsan Kidambi

Authors
  1. Stephen L. Hayward
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Srivatsan Kidambi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Srivatsan Kidambi .

Editor information

Editors and Affiliations

  1. Vivian L. Smith Department of Neurosurgery, University of Texas Health Science, Center at Houston, Houston, Texas, USA

    Rachael W. Sirianni

  2. Department of Mechanical Engineering, Virginia Tech, Blacksburg, Virginia, USA

    Bahareh Behkam

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Hayward, S.L., Kidambi, S. (2018). CD44 Targeted Lipid Nanoparticles for MicroRNA Therapy. In: Sirianni, R., Behkam, B. (eds) Targeted Drug Delivery. Methods in Molecular Biology, vol 1831. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8661-3_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-8661-3_8

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8659-0

  • Online ISBN: 978-1-4939-8661-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation