Advertisement

Preparation and Evaluation of Folate Receptor Mediated Targeting Liposomes

Living reference work entry
Part of the Biomaterial Engineering book series (BIOENG)

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.

Keywords

Folate Ligand-modified targeting liposome Cancer Drug delivery Post-insertion 

References

  1. Allen TM, Cullis PR (2013) Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev 65:36–48CrossRefGoogle Scholar
  2. Anderson RG, Kamen BA, Rothberg KG, Lacey SW (1992a) Potocytosis: sequestration and transport of small molecules by caveolae. Science 255:410–411CrossRefGoogle Scholar
  3. Anderson RGW, Kamen BA, Rothberg KG, Lacey SW (1992b) Potocytosis – sequestration and transport of small molecules by caveolae. Science 255:410–411CrossRefGoogle Scholar
  4. Antony AC (1992) The biological chemistry of folate receptors. Blood 79:2807–2820Google Scholar
  5. Choi SW, Mason JB (2000) Folate and carcinogenesis: an integrated scheme. J Nutr 130:129–132CrossRefGoogle Scholar
  6. 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 63:136–151CrossRefGoogle Scholar
  7. 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 10:289–298CrossRefGoogle Scholar
  8. 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 1513:207–216CrossRefGoogle Scholar
  9. Immordino ML, Dosio F, Cattel L (2006) Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int J Nanomedicine 1:297–315CrossRefGoogle Scholar
  10. Ishida T, Iden DL, Allen TM (1999) A combinatorial approach to producing sterically stabilized (stealth) immunoliposomal drugs. FEBS Lett 460:129–133CrossRefGoogle Scholar
  11. Kamen BA, Capdevila A (1986) Receptor-mediated folate accumulation is regulated by the cellular folate content. P Natl Acad Sci USA 83:5983–5987CrossRefGoogle Scholar
  12. 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 263:13602–13609Google Scholar
  13. Lee RJ, Low PS (1994) Delivery of liposomes into cultured kb cells via folate receptor-mediated endocytosis. J Biol Chem 269:3198–3204Google Scholar
  14. Lee RJ, Low PS (1995) Folate-mediated tumor-cell targeting of liposome-entrapped doxorubicin in-vitro. BBA-Biomembranes 1233:134–144CrossRefGoogle Scholar
  15. Lee RJ, Low PS (1997) Folate-targeted liposomes for drug delivery. J Liposome Res 7:455–466CrossRefGoogle Scholar
  16. 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 41:120–129CrossRefGoogle Scholar
  17. Lu Y, Low PS (2002) Folate-mediated delivery of macromolecular anticancer therapeutic agents. Adv Drug Deliv Rev 54:675–693CrossRefGoogle Scholar
  18. Maruyama K (2011) Intracellular targeting delivery of liposomal drugs to solid tumors based on EPR effects. Adv Drug Deliv Rev 63:161–169CrossRefGoogle Scholar
  19. Matherly LH, Hou Z, Deng Y (2007) Human reduced folate carrier: translation of basic biology to cancer etiology and therapy. Cancer Metastasis Rev 26:111–128CrossRefGoogle Scholar
  20. 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 88:11460–11464CrossRefGoogle Scholar
  21. Park JW (2002) Liposome-based drug delivery in breast cancer treatment. Breast Cancer Res : BCR 4:95–99CrossRefGoogle Scholar
  22. 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 338:284–293CrossRefGoogle Scholar
  23. 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 110:637–649CrossRefGoogle Scholar
  24. Saul JM, Annapragada A, Natarajan JV, Bellamkonda RV (2003) Controlled targeting of liposomal doxorubicin via the folate receptor in vitro. J Control Release 92:49–67CrossRefGoogle Scholar
  25. 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 33:1209–1215CrossRefGoogle Scholar
  26. Toffoli G, Cernigoi C, Russo A, Gallo A, Bagnoli M, Boiocchi M (1997) Overexpression of folate binding protein in ovarian cancers. Int J Cancer 74:193–198CrossRefGoogle Scholar
  27. 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 6:2716–2719CrossRefGoogle Scholar
  28. 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 386:243–246CrossRefGoogle Scholar
  29. 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 60:12–21CrossRefGoogle Scholar
  30. Yan Y, Qi XR (2008) Preparation and properties of folate receptor-targeted cationic liposomes. Yao xue xue bao = Acta pharmaceutica Sinica 43:1134–1139Google Scholar
  31. Zalipsky S, Brandeis E, Newman MS, Woodle MC (1994) Long circulating, cationic liposomes containing amino-PEG-phosphatidylethanolamine. FEBS Lett 353:71–74CrossRefGoogle Scholar
  32. 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 117:281–290CrossRefGoogle Scholar
  33. Zhao XB, Li H, Lee RJ (2008) Targeted drug delivery via folate receptors. Expert Opin Drug Del 5:309–319CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2018

Authors and Affiliations

  1. 1.Department of Industrial and Physical Pharmacy, College of PharmacyPurdue UniversityWest LafayetteUSA

Personalised recommendations