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Utilizing the folate receptor for active targeting of cancer nanotherapeutics

Zwicke, Grant L., Ali Mansoori, G., Jeffery, Constance J.·2012·Nano Reviews
DOI 10.3402/nano.v3i0.18496PMC PMC3521101
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Crossref · 10.3402/nano.v3i0.18496

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Fig. 1 The vasculature of cancerous tissues can be more leaky than that of healthy tissues. This difference in leakiness can be exploited in anticancer drug delivery. Vasculature of the tissue on the left is normal while the tissue on the right is leaky. The nanoparticles passively enter through the leaky vasculature into the tumor tissue due to the enhanced permeability and retention (EPR) effect. (Illustrated by Samantha L. Lindberg).
Fig. 1 The vasculature of cancerous tissues can be more leaky than that of healthy tissues. This difference in leakiness can be exploited in anticancer drug delivery. Vasculature of the tissue on the left is normal while the tissue on the right is leaky. The nanoparticles passively enter through the leaky vasculature into the tumor tissue due to the enhanced permeability and retention (EPR) effect. (Illustrated by Samantha L. Lindberg).CC BY · PubMed Central
Fig. 2 A variety of nanoparticle materials are being studied for use in imaging and drug targeting. These include liposomes, quantum dots (QD), gold-nanoshells, mesoporous materials, micelles, magnetic nanoparticles, dendrimers, and CNTs. (Illustrated by Grant Zwicke).
Fig. 2 A variety of nanoparticle materials are being studied for use in imaging and drug targeting. These include liposomes, quantum dots (QD), gold-nanoshells, mesoporous materials, micelles, magnetic nanoparticles, dendrimers, and CNTs. (Illustrated by Grant Zwicke).CC BY · PubMed Central
Fig. 3 Structures of the molecules (A) 99mTc-EC20, (B) methotrexate, and (C) folic acid.
Fig. 3 Structures of the molecules (A) 99mTc-EC20, (B) methotrexate, and (C) folic acid.CC BY · PubMed Central
Fig. 4 Overview of the folate cycle. The folate cycle is essential for rapidly growing cells. In cells, the endocytosis of folate is chiefly mediated through the alpha, beta, and gamma folate receptors (FOLR1-3) which have high affinities. (Reproduced with permission from Garcia-Bennett, Nees, Fadeel, 2011) (6).
Fig. 4 Overview of the folate cycle. The folate cycle is essential for rapidly growing cells. In cells, the endocytosis of folate is chiefly mediated through the alpha, beta, and gamma folate receptors (FOLR1-3) which have high affinities. (Reproduced with permission from Garcia-Bennett, Nees, Fadeel, 2011) (6).CC BY · PubMed Central
Fig. 5 Receptor-mediated endocytosis of a drug conjugated to folate. (1) The drug–folate conjugate binds to folate receptors in caveolae. (2) Membrane invagination occurs and the drug–folate conjugate is engulfed by the cell and internalized by the endocytotic pathway. (3) Drug release is initiated by the low pH environment of the endosome. (4) Drug and imaging agents are released into the cell. (5) The folate receptor can be recycled and returned to the cell membrane. (Illustrated by Samantha L. Lindberg).
Fig. 5 Receptor-mediated endocytosis of a drug conjugated to folate. (1) The drug–folate conjugate binds to folate receptors in caveolae. (2) Membrane invagination occurs and the drug–folate conjugate is engulfed by the cell and internalized by the endocytotic pathway. (3) Drug release is initiated by the low pH environment of the endosome. (4) Drug and imaging agents are released into the cell. (5) The folate receptor can be recycled and returned to the cell membrane. (Illustrated by Samantha L. Lindberg).CC BY · PubMed Central
Fig. 6 An example of an image resulting from a small animal that has undergone micro-SPECT imaging. The fluorescent blue areas indicate the locations of cancer cells. (Reproduced with permission from Bioscan) (67).
Fig. 6 An example of an image resulting from a small animal that has undergone micro-SPECT imaging. The fluorescent blue areas indicate the locations of cancer cells. (Reproduced with permission from Bioscan) (67).CC BY · PubMed Central
Fig. 7 Structure of folate linked gold nanoparticles and doxorubicin-polyethylene glycol-folate nanoaggregates (A) folate-4-Aminothiophenol-gold nanoparticle (FOL-4Atp-AuNP) (B) folate-6-mercapto-1-hexanol-gold nanoparticle (FOL-MH-AuNP) (C) doxorubicin-polyethylene glycol-folate (DOX–PEG–FOL) nanoaggregates.
Fig. 7 Structure of folate linked gold nanoparticles and doxorubicin-polyethylene glycol-folate nanoaggregates (A) folate-4-Aminothiophenol-gold nanoparticle (FOL-4Atp-AuNP) (B) folate-6-mercapto-1-hexanol-gold nanoparticle (FOL-MH-AuNP) (C) doxorubicin-polyethylene glycol-folate (DOX–PEG–FOL) nanoaggregates.CC BY · PubMed Central

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Research works printed but not linked: 5

  1. Garin-Chesa P, Campbell I, Saigo PE, Lewis JL, Old LJ, Rettig WJ. Trophoblast and ovarian cancer antigen LK26: sensitivity and specificity in immunopathology and molecular identification as a folate-binding protein. Am J Pathol. 1993; 142: 557–67.
  2. 10.1148/radiology.219.2.r01ma19316 · DOI · Paper page
  3. 10.1002/cmdc.200800091 · DOI
  4. Lasic DD, Papahadjopoulos D. Medical application of liposomes. Elsevier. Amsterdam The Netherlands, 1998
  5. 10.2147/IJN.S27823 · DOI

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Metadata

Authors
Zwicke, G. L., Ali Mansoori, G., & Jeffery, C. J.
Affiliations
,
Venue
Nano Reviews
Publisher
Informa UK Limited
Published
2012-01
Volume
3
Issue
1
ISSN
2000-5121
DOI
10.3402/nano.v3i0.18496
PMC
PMC3521101
Cited by
458
References
2
Language
en

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