Skip to main content
SpringerLink
Log in

Preparation and Evaluation of Folate Receptor Mediated Targeting Liposomes

  • Living reference work entry
  • First Online:
Liposome-Based Drug Delivery Systems

Part of the book series: Biomaterial Engineering ((BIOENG))

  • 174 Accesses

Abstract

Liposomes have been well used as an efficient delivery system for cancer therapy. Overexpressed folate receptor is a confirmed tumor-associated antigen that binds folate and folate-targeted liposomes with very high affinity. Folate receptor shuttles these bound molecules inside cells via an endocytic mechanism. It is described as an efficient folate-modified liposome preparation method in this chapter based on a post-insertion technique. Conjugate of 1,2-dipalmitoyl-sn-glycerophosphoethanolamine-polyethylene glycol-folate (DPPE-PEG-folate), derived from PEG with molecular masses of 2000 Da, is synthesized and characterized by 1H NMR and mass spectrometer. By micellization of folate conjugates and their controlled insertion into preformed liposomes, DOX-loaded folate-targeted liposome is prepared. The selectivity and specificity of folate target liposome is evaluated in KB, C6, and cortical cells. It was found that KB cells took up significant amounts of DOX relative to the C6 cells or relative to normal cortical tissue.

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

Access this chapter

Log in via an institution

Institutional subscriptions

References

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

    Article  CAS  Google Scholar 

  • Anderson RG, Kamen BA, Rothberg KG, Lacey SW (1992a) Potocytosis: sequestration and transport of small molecules by caveolae. Science 255:410–411

    Article  CAS  Google Scholar 

  • Anderson RGW, Kamen BA, Rothberg KG, Lacey SW (1992b) Potocytosis – sequestration and transport of small molecules by caveolae. Science 255:410–411

    Article  CAS  Google Scholar 

  • Antony AC (1992) The biological chemistry of folate receptors. Blood 79:2807–2820

    CAS  Google Scholar 

  • Choi SW, Mason JB (2000) Folate and carcinogenesis: an integrated scheme. J Nutr 130:129–132

    Article  CAS  Google Scholar 

  • Fang J, Nakamura H, Maeda H (2011) The EPR effect: unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv Drug Deliv Rev 63:136–151

    Article  CAS  Google Scholar 

  • Gabizon A, Horowitz AT, Goren D, Tzemach D, Mandelbaum-Shavit F, Qazen MM, Zalipsky S (1999) Targeting folate receptor with folate linked to extremities of poly(ethylene glycol)-grafted liposomes: in vitro studies. Bioconjug Chem 10:289–298

    Article  CAS  Google Scholar 

  • Iden DL, Allen TM (2001) In vitro and in vivo comparison of immunoliposomes made by conventional coupling techniques with those made by a new post-insertion approach. BBA-Biomembranes 1513:207–216

    Article  CAS  Google Scholar 

  • Immordino ML, Dosio F, Cattel L (2006) Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int J Nanomedicine 1:297–315

    Article  CAS  Google Scholar 

  • Ishida T, Iden DL, Allen TM (1999) A combinatorial approach to producing sterically stabilized (stealth) immunoliposomal drugs. FEBS Lett 460:129–133

    Article  CAS  Google Scholar 

  • Kamen BA, Capdevila A (1986) Receptor-mediated folate accumulation is regulated by the cellular folate content. P Natl Acad Sci USA 83:5983–5987

    Article  CAS  Google Scholar 

  • Kamen BA, Wang MT, Streckfuss AJ, Peryea X, Anderson RGW (1988) Delivery of folates to the cytoplasm of Ma104 cells is mediated by a surface-membrane receptor that recycles. J Biol Chem 263:13602–13609

    CAS  Google Scholar 

  • Lee RJ, Low PS (1994) Delivery of liposomes into cultured kb cells via folate receptor-mediated endocytosis. J Biol Chem 269:3198–3204

    CAS  Google Scholar 

  • Lee RJ, Low PS (1995) Folate-mediated tumor-cell targeting of liposome-entrapped doxorubicin in-vitro. BBA-Biomembranes 1233:134–144

    Article  Google Scholar 

  • Lee RJ, Low PS (1997) Folate-targeted liposomes for drug delivery. J Liposome Res 7:455–466

    Article  CAS  Google Scholar 

  • Low PS, Henne WA, Doorneweerd DD (2008) Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases. Acc Chem Res 41:120–129

    Article  CAS  Google Scholar 

  • Lu Y, Low PS (2002) Folate-mediated delivery of macromolecular anticancer therapeutic agents. Adv Drug Deliv Rev 54:675–693

    Article  CAS  Google Scholar 

  • Maruyama K (2011) Intracellular targeting delivery of liposomal drugs to solid tumors based on EPR effects. Adv Drug Deliv Rev 63:161–169

    Article  CAS  Google Scholar 

  • Matherly LH, Hou Z, Deng Y (2007) Human reduced folate carrier: translation of basic biology to cancer etiology and therapy. Cancer Metastasis Rev 26:111–128

    Article  CAS  Google Scholar 

  • Papahadjopoulos D, Allen TM, Gabizon A, Mayhew E, Matthay K, Huang SK, Lee KD, Woodle MC, Lasic DD, Redemann C, Martin FJ (1991) Sterically stabilized liposomes – improvements in pharmacokinetics and antitumor therapeutic efficacy. P Natl Acad Sci USA 88:11460–11464

    Article  CAS  Google Scholar 

  • Park JW (2002) Liposome-based drug delivery in breast cancer treatment. Breast Cancer Res : BCR 4:95–99

    Article  CAS  Google Scholar 

  • Parker N, Turk MJ, Westrick E, Lewis JD, Low PS, Leamon CP (2005) Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay. Anal Biochem 338:284–293

    Article  CAS  Google Scholar 

  • Rothberg KG, Ying YS, Kolhouse JF, Kamen BA, Anderson RGW (1990) The glycophospholipid-linked folate receptor internalizes folate without entering the clathrin-coated pit endocytic pathway. J Cell Biol 110:637–649

    Article  CAS  Google Scholar 

  • Saul JM, Annapragada A, Natarajan JV, Bellamkonda RV (2003) Controlled targeting of liposomal doxorubicin via the folate receptor in vitro. J Control Release 92:49–67

    Article  CAS  Google Scholar 

  • Shen F, Ross JF, Wang X, Ratnam M (1994) Identification of a novel folate receptor, a truncated receptor, and receptor type beta in hematopoietic cells: cDNA cloning, expression, immunoreactivity, and tissue specificity. Biochemistry-Us 33:1209–1215

    Article  CAS  Google Scholar 

  • Toffoli G, Cernigoi C, Russo A, Gallo A, Bagnoli M, Boiocchi M (1997) Overexpression of folate binding protein in ovarian cancers. Int J Cancer 74:193–198

    Article  CAS  Google Scholar 

  • Torchilin VP, Klibanov AL, Huang L, Odonnell S, Nossiff ND, Khaw BA (1992) Targeted accumulation of polyethylene glycol-coated immunoliposomes in infarcted rabbit myocardium. FASEB J 6:2716–2719

    Article  CAS  Google Scholar 

  • Uster PS, Allen TM, Daniel BE, Mendez CJ, Newman MS, Zhu GZ (1996) Insertion of poly(ethylene glycol) derivatized phospholipid into pre-formed liposomes results in prolonged in vivo circulation time. FEBS Lett 386:243–246

    Article  CAS  Google Scholar 

  • van der Heijden JW, Oerlemans R, Dijkmans BAC, Qi H, van der Laken CJ, Lems WF, Jackman AL, Kraan MC, Tak PP, Ratnam M, Jansen G (2009) Folate receptor beta as a potential delivery route for novel folate antagonists to macrophages in the synovial tissue of rheumatoid arthritis patients. Arthritis Rheum-Us 60:12–21

    Article  Google Scholar 

  • Yan Y, Qi XR (2008) Preparation and properties of folate receptor-targeted cationic liposomes. Yao xue xue bao = Acta pharmaceutica Sinica 43:1134–1139

    CAS  Google Scholar 

  • Zalipsky S, Brandeis E, Newman MS, Woodle MC (1994) Long circulating, cationic liposomes containing amino-PEG-phosphatidylethanolamine. FEBS Lett 353:71–74

    Article  CAS  Google Scholar 

  • Zhang Y, Qi XR, Gao Y, Wei L, Maitani Y, Nagai T (2007) Mechanisms of co-modified liver-targeting liposomes as gene delivery carriers based on cellular uptake and antigens inhibition effect. J Control Release 117:281–290

    Article  CAS  Google Scholar 

  • Zhao XB, Li H, Lee RJ (2008) Targeted drug delivery via folate receptors. Expert Opin Drug Del 5:309–319

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, IN, USA

    Wei Gao

Authors
  1. Wei Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wei Gao .

Editor information

Editors and Affiliations

  1. Department of Pharmaceutics, Peking University Department of Pharmaceutics, Beijing, China

    Wan-Liang Lu

  2. Department of Pharmaceutics, Peking University Department of Pharmaceutics, Beijing, China

    Xiang-Rong Qi

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer-Verlag GmbH Germany

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Gao, W. (2018). Preparation and Evaluation of Folate Receptor Mediated Targeting Liposomes. In: Lu, WL., Qi, XR. (eds) Liposome-Based Drug Delivery Systems. Biomaterial Engineering. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-49231-4_12-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-49231-4_12-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-49231-4

  • Online ISBN: 978-3-662-49231-4

  • eBook Packages: Springer Reference Chemistry and Mat. ScienceReference Module Physical and Materials ScienceReference Module Chemistry, Materials and Physics

Publish with us

Policies and ethics

Search

Navigation