Skip to main content
SpringerLink
Log in

Delivery of Cargo to Lysosomes Using GNeosomes

  • Protocol
  • First Online:
Lysosomes

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1594))

Abstract

Liposomes have been used to improve the intracellular delivery of a variety of cargos. Encapsulation of cargos in liposomes leads to improved plasma half-lives and minimized degradation. Here, we present a method for improving the selective delivery of liposomes to the lysosomes using a guanidinylated neomycin (GNeo) transporter. The method for synthesizing GNeo-lipids, incorporating them into liposomes, and the enhanced lysosomal delivery of encapsulated cargo are presented. GNeo-liposomes, termed GNeosomes, are capable of delivering a fluorescent dye to the lysosomes of Chinese hamster ovary cells as shown using confocal microscopy. GNeosomes can also be used to deliver therapeutic quantities of lysosomal enzymes to fibroblasts isolated from patients with a lysosomal storage disorder.

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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. Pattni BS, Chupin VV, Torchilin VP (2015) New developments in liposomal drug delivery. Chem Rev 115(19):10938–10966. doi:10.1021/acs.chemrev.5b00046

    Article  CAS  PubMed  Google Scholar 

  2. Allen TM, Cullis PR (2013) Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev 65(1):36–48

    Article  CAS  PubMed  Google Scholar 

  3. Appelqvist H, Waster P, Kagedal K, Ollinger K (2013) The lysosome: from waste bag to potential therapeutic target. J Mol Cell Biol 5(4):214–226. doi:10.1093/jmcb/mjt022

    Article  CAS  PubMed  Google Scholar 

  4. Fehrenbacher N, Jaattela M (2005) Lysosomes as targets for cancer therapy. Cancer Res 65(8):2993–2995. doi:10.1158/0008-5472.can-05-0476

    CAS  PubMed  Google Scholar 

  5. Grubb JH, Vogler C, Sly WS (2010) New strategies for enzyme replacement therapy for lysosomal storage diseases. Rejuvenation Res 13(2–3):229–236. doi:10.1089/rej.2009.0920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sarrazin S, Wilson B, Sly WS, Tor Y, Esko JD (2010) Guanidinylated neomycin mediates heparan sulfate-dependent transport of active enzymes to lysosomes. Mol Ther 18(7):1268–1274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Maniganda S, Sankar V, Nair JB, Raghu KG, Maiti KK (2014) A lysosome-targeted drug delivery system based on sorbitol backbone towards efficient cancer therapy. Org Biomol Chem 12(34):6564–6569. doi:10.1039/c4ob01153h

    Article  CAS  PubMed  Google Scholar 

  8. Xiang HJ, Deng Q, An L, Guo M, Yang SP, Liu JG (2016) Tumor cell specific and lysosome-targeted delivery of nitric oxide for enhanced photodynamic therapy triggered by 808 nm near-infrared light. Chem Commun (Camb) 52(1):148–151. doi:10.1039/c5cc07006f

    Article  CAS  Google Scholar 

  9. Wexselblatt E, Esko JD, Tor Y (2015) GNeosomes: highly lysosomotropic nanoassemblies for lysosomal delivery. ACS Nano 9(4):3961–3968. doi:10.1021/nn507382n

    Article  CAS  PubMed  Google Scholar 

  10. Zhang Z, Zhang X, Xu X, Li Y, Li Y, Zhong D, He Y, Gu Z (2015) Virus-inspired mimics based on dendritic lipopeptides for efficient tumor-specific infection and systemic drug delivery. Adv Funct Mater 25(33):5250–5260. doi:10.1002/adfm.201502049

    Article  CAS  Google Scholar 

  11. Fry DW, White JC, Goldman ID (1978) Rapid separation of low molecular weight solutes from liposomes without dilution. Anal Biochem 90(2):809–815

    Article  CAS  PubMed  Google Scholar 

  12. Natarajan A, Du W, Xiong CY, DeNardo GL, DeNardo SJ, Gervay-Hague J (2007) Construction of di-scFv through a trivalent alkyne-azide 1,3-dipolar cycloaddition. Chem Commun (Camb) (7):695–697. doi:10.1039/b611636a

  13. Inoue M, Tong W, Esko JD, Tor Y (2013) Aggregation-mediated macromolecular uptake by a molecular transporter. ACS Chem Biol 8(7):1383–1388. doi:10.1021/cb400172h

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kojima R, Takakura H, Ozawa T, Tada Y, Nagano T, Urano Y (2013) Rational design and development of near-infrared-emitting firefly luciferins available in vivo. Angew Chem Int Ed 52(4):1175–1179. doi:10.1002/anie.201205151

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, 92093-0358, USA

    Kristina M. Hamill, Ezequiel Wexselblatt & Yitzhak Tor

  2. Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, 92093-0687, USA

    Wenyong Tong & Jeffrey D. Esko

Authors
  1. Kristina M. Hamill
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ezequiel Wexselblatt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wenyong Tong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jeffrey D. Esko
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yitzhak Tor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yitzhak Tor .

Editor information

Editors and Affiliations

  1. Experimental Pathology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden

    Karin Öllinger

  2. Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden

    Hanna Appelqvist

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media LLC

About this protocol

Cite this protocol

Hamill, K.M., Wexselblatt, E., Tong, W., Esko, J.D., Tor, Y. (2017). Delivery of Cargo to Lysosomes Using GNeosomes. In: Öllinger, K., Appelqvist, H. (eds) Lysosomes. Methods in Molecular Biology, vol 1594. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6934-0_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-6934-0_9

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6932-6

  • Online ISBN: 978-1-4939-6934-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation