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n2:pmcid
PMC0
bibo:doi
10.1083%2Fjcb.200910104
n7:contains
_:vb7259863
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_:vb7259863
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n7:Section
dc:title
introduction
n7:contains
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Traditionally, such molecules were detected with antibodies, but screening of peptide and aptamer libraries has greatly expanded the number of tools available for selective binding to tumor cells (for reviews see Ruoslahti, >>2002<<; Peer et al., 2007).
n2:mentions
n3:12635171
Subject Item
_:vb7259865
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such molecules were detected with antibodies, but screening of peptide and aptamer libraries has greatly expanded the number of tools available for selective binding to tumor cells (for reviews see Ruoslahti, 2002; Peer et al., >>2007<<). Leukemia and lymphoma treatments with antibodies conjugated to a radioisotope have been in clinical use for several years (Sharkey and Goldenberg, 2005).
n2:mentions
n3:18654426
Subject Item
_:vb7259866
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rdf:value
Leukemia and lymphoma treatments with antibodies conjugated to a radioisotope have been in clinical use for several years (Sharkey and Goldenberg, >>2005<<). However, this approach has not been as successful with solid tumors. The apparent reason is the difficulty in delivering drugs into these tumors; drugs only penetrate a few cell diameters into the extravascular tumor tissue from blood
n2:mentions
n3:15653660
Subject Item
_:vb7259867
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The apparent reason is the difficulty in delivering drugs into these tumors; drugs only penetrate a few cell diameters into the extravascular tumor tissue from blood vessels (Hambley and Hait, >>2009<<). This low penetration appears to arise from two main factors: first, tumor vessels are poorly perfused with blood and are dysfunctional, which limits the delivery of blood-borne compounds to tumors (Jain, 1999). Second, tumors have a
n2:mentions
n3:19208831
Subject Item
_:vb7259868
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n2:Context
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This low penetration appears to arise from two main factors: first, tumor vessels are poorly perfused with blood and are dysfunctional, which limits the delivery of blood-borne compounds to tumors (Jain, >>1999<<). Second, tumors have a high interstitial pressure thought to result from dysfunctional lymphatics, which causes tissue fluid to flow out of the tumor, working against diffusion of drugs from the blood vessels into the tumor (Jain, 1999;
n2:mentions
n3:11701489
Subject Item
_:vb7259869
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n2:Context
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Second, tumors have a high interstitial pressure thought to result from dysfunctional lymphatics, which causes tissue fluid to flow out of the tumor, working against diffusion of drugs from the blood vessels into the tumor (Jain, >>1999<<; Heldin et al., 2004).
n2:mentions
n3:11701489
Subject Item
_:vb7259870
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n2:Context
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a high interstitial pressure thought to result from dysfunctional lymphatics, which causes tissue fluid to flow out of the tumor, working against diffusion of drugs from the blood vessels into the tumor (Jain, 1999; Heldin et al., >>2004<<). The leakiness of tumor vessels partially makes up for the poor penetration (the so-called enhanced permeability and retention [EPR] effect), but EPR is not very effective, and its size dependency and variability from tumor to tumor
n2:mentions
n3:15510161
Subject Item
_:vb7259871
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makes up for the poor penetration (the so-called enhanced permeability and retention [EPR] effect), but EPR is not very effective, and its size dependency and variability from tumor to tumor limit its usefulness (Maeda et al., >>2000<<; Iyer et al., 2006; Sugahara et al., 2009). Interstitial fibrosis can further retard the diffusion of compounds through tumors (Olive et al., 2009).
n2:mentions
n3:10699287
Subject Item
_:vb7259872
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the poor penetration (the so-called enhanced permeability and retention [EPR] effect), but EPR is not very effective, and its size dependency and variability from tumor to tumor limit its usefulness (Maeda et al., 2000; Iyer et al., >>2006<<; Sugahara et al., 2009). Interstitial fibrosis can further retard the diffusion of compounds through tumors (Olive et al., 2009).
n2:mentions
n3:16935749
Subject Item
_:vb7259873
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n2:Context
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(the so-called enhanced permeability and retention [EPR] effect), but EPR is not very effective, and its size dependency and variability from tumor to tumor limit its usefulness (Maeda et al., 2000; Iyer et al., 2006; Sugahara et al., >>2009<<). Interstitial fibrosis can further retard the diffusion of compounds through tumors (Olive et al., 2009).
n2:mentions
n3:19962669
Subject Item
_:vb7259874
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n2:Context
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Interstitial fibrosis can further retard the diffusion of compounds through tumors (Olive et al., >>2009<<). Targeting treatments to selective markers in tumor vessels does not suffer from some of these drawbacks of targeting tumor cells; in particular, no tissue penetration is required for the compound to reach its target. The luminal side of
n2:mentions
n3:19460966
Subject Item
_:vb7259875
rdf:type
n2:Context
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being tortuous, uneven in diameter, and leaky, tumor vessels express various cell surface and extracellular matrix proteins that normal vessels do not express or do so at much lower levels than tumor vessels (for review see Ruoslahti, >>2002<<). The expression of many of these proteins in tumor vessels is associated with angiogenesis, and they are often functionally important in that process (Hanahan and Folkman, 1996; Alitalo and Carmeliet, 2002).
n2:mentions
n3:12635171
Subject Item
_:vb7259876
rdf:type
n2:Context
rdf:value
The expression of many of these proteins in tumor vessels is associated with angiogenesis, and they are often functionally important in that process (Hanahan and Folkman, >>1996<<; Alitalo and Carmeliet, 2002).
n2:mentions
n3:8756718
Subject Item
_:vb7259877
rdf:type
n2:Context
rdf:value
The expression of many of these proteins in tumor vessels is associated with angiogenesis, and they are often functionally important in that process (Hanahan and Folkman, 1996; Alitalo and Carmeliet, >>2002<<). Tumors also contain lymphatic vessels, and many tumors produce growth factors that stimulate lymphangiogenesis (Karpanen and Alitalo, 2008). Lymphatics are not necessary for tumor growth but are important conduits of metastasis. Like
n2:mentions
n3:12086857
Subject Item
_:vb7259878
rdf:type
n2:Context
rdf:value
Tumors also contain lymphatic vessels, and many tumors produce growth factors that stimulate lymphangiogenesis (Karpanen and Alitalo, >>2008<<). Lymphatics are not necessary for tumor growth but are important conduits of metastasis. Like tumor blood vessels, tumor lymphatics can also express specific molecular markers.
n2:mentions
n3:18039141
Subject Item
_:vb7259879
rdf:type
n2:Context
rdf:value
Screening of phage-displayed peptide libraries, particularly when performed in vivo, has provided a very useful discovery tool for vascular markers in tumor vessels and elsewhere (Pasqualini and Ruoslahti, >>1996<<). A major advantage of the in vivo phage screening is that it is unbiased in revealing what works in vivo.
n2:mentions
n3:8598934
Subject Item
_:vb7259880
rdf:type
n2:Context
rdf:value
Other unbiased methods, such as antibody-based screens (Jacobson et al., >>1996<<), cloning strategies (Carson-Walter et al., 2001), and in vivo biotinylation (Borgia et al., 2010), have also been used successfully in analyzing tumor vasculature.
n2:mentions
n3:8597963
Subject Item
_:vb7259881
rdf:type
n2:Context
rdf:value
Other unbiased methods, such as antibody-based screens (Jacobson et al., 1996), cloning strategies (Carson-Walter et al., >>2001<<), and in vivo biotinylation (Borgia et al., 2010), have also been used successfully in analyzing tumor vasculature.
n2:mentions
n3:11559528
Subject Item
_:vb7259882
rdf:type
n2:Context
rdf:value
Other unbiased methods, such as antibody-based screens (Jacobson et al., 1996), cloning strategies (Carson-Walter et al., 2001), and in vivo biotinylation (Borgia et al., >>2010<<), have also been used successfully in analyzing tumor vasculature.
n2:mentions
n3:19996283
Subject Item
_:vb7259883
rdf:type
n2:Context
rdf:value
Phage screening has uncovered a large number of tumor-homing peptides that have been used to identify the corresponding binding protein (receptor). An early study on tumor-homing peptides (Arap et al., >>1998<<) validated the method by producing tumor-homing peptides with RGD (arginine/glycine/aspartice acid) and NGR (asparagine/glycine/arginine) motifs, which had been previously identified in screens for integrin-binding peptides performed in
n2:mentions
n3:9430587
Subject Item
_:vb7259884
rdf:type
n2:Context
rdf:value
F3 is an example of a novel tumor-homing peptide identified by in vivo phage screening (Porkka et al., >>2002<<). F3 binds to nucleolin, which is ubiquitous as an intracellular protein but is expressed at the cell surface of endothelial cells and tumor cells in vivo (Christian et al., 2003). In vitro, all cells seem to be positive for cell surface
n2:mentions
n3:12032302
Subject Item
_:vb7259885
rdf:type
n2:Context
rdf:value
F3 binds to nucleolin, which is ubiquitous as an intracellular protein but is expressed at the cell surface of endothelial cells and tumor cells in vivo (Christian et al., >>2003<<). In vitro, all cells seem to be positive for cell surface nucleolin (Borer et al., 1989; Bonnet et al., 1996) presumably because cultured cells resemble cells that have been activated in vivo. Cell surface nucleolin is an angiogenesis
n2:mentions
n3:14638862
Subject Item
_:vb7259886
rdf:type
n2:Context
rdf:value
In vitro, all cells seem to be positive for cell surface nucleolin (Borer et al., >>1989<<; Bonnet et al., 1996) presumably because cultured cells resemble cells that have been activated in vivo.
n2:mentions
n3:2914325
Subject Item
_:vb7259887
rdf:type
n2:Context
rdf:value
In vitro, all cells seem to be positive for cell surface nucleolin (Borer et al., 1989; Bonnet et al., >>1996<<) presumably because cultured cells resemble cells that have been activated in vivo.
n2:mentions
n3:8798749
Subject Item
_:vb7259888
rdf:type
n2:Context
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Cell surface nucleolin is an angiogenesis marker that is both a suitable target for drug delivery (Christian et al., >>2001<<; Reddy et al., 2006; Henke et al., 2008; Drecoll et al., 2009) and involved in the angiogenesis process (Fogal et al., 2009).
n2:mentions
n3:11084048
Subject Item
_:vb7259889
rdf:type
n2:Context
rdf:value
Cell surface nucleolin is an angiogenesis marker that is both a suitable target for drug delivery (Christian et al., 2001; Reddy et al., >>2006<<; Henke et al., 2008; Drecoll et al., 2009) and involved in the angiogenesis process (Fogal et al., 2009).
n2:mentions
n3:17121886
Subject Item
_:vb7259890
rdf:type
n2:Context
rdf:value
Cell surface nucleolin is an angiogenesis marker that is both a suitable target for drug delivery (Christian et al., 2001; Reddy et al., 2006; Henke et al., >>2008<<; Drecoll et al., 2009) and involved in the angiogenesis process (Fogal et al., 2009).
n2:mentions
n3:18176556
Subject Item
_:vb7259891
rdf:type
n2:Context
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Cell surface nucleolin is an angiogenesis marker that is both a suitable target for drug delivery (Christian et al., 2001; Reddy et al., 2006; Henke et al., 2008; Drecoll et al., >>2009<<) and involved in the angiogenesis process (Fogal et al., 2009).
n2:mentions
n3:19479088
Subject Item
_:vb7259892
rdf:type
n2:Context
rdf:value
nucleolin is an angiogenesis marker that is both a suitable target for drug delivery (Christian et al., 2001; Reddy et al., 2006; Henke et al., 2008; Drecoll et al., 2009) and involved in the angiogenesis process (Fogal et al., >>2009<<). The in vivo screening of phage libraries has also produced several potent tumor-homing peptides, the target molecules of which remain to be identified (Hoffman et al., 2003; Joyce et al., 2003; Järvinen and Ruoslahti, 2007; Chang et al.
n2:mentions
n3:19225898
Subject Item
_:vb7259893
rdf:type
n2:Context
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The in vivo screening of phage libraries has also produced several potent tumor-homing peptides, the target molecules of which remain to be identified (Hoffman et al., >>2003<<; Joyce et al., 2003; Järvinen and Ruoslahti, 2007; Chang et al., 2009).
n2:mentions
n3:14667505
Subject Item
_:vb7259894
rdf:type
n2:Context
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The in vivo screening of phage libraries has also produced several potent tumor-homing peptides, the target molecules of which remain to be identified (Hoffman et al., 2003; Joyce et al., >>2003<<; Järvinen and Ruoslahti, 2007; Chang et al., 2009).
n2:mentions
n3:14667506
Subject Item
_:vb7259895
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n2:Context
rdf:value
The in vivo screening of phage libraries has also produced several potent tumor-homing peptides, the target molecules of which remain to be identified (Hoffman et al., 2003; Joyce et al., 2003; Järvinen and Ruoslahti, >>2007<<; Chang et al., 2009).
n2:mentions
n3:17600129
Subject Item
_:vb7259896
rdf:type
n2:Context
rdf:value
in vivo screening of phage libraries has also produced several potent tumor-homing peptides, the target molecules of which remain to be identified (Hoffman et al., 2003; Joyce et al., 2003; Järvinen and Ruoslahti, 2007; Chang et al., >>2009<<).
n2:mentions
n3:19276080
Subject Item
_:vb7259897
rdf:type
n2:Context
rdf:value
In addition to aforementioned nucleolin, the cytoplasmic proteins annexin1 (Oh et al., >>2004<<) and plectin-1 (Kelly et al., 2008) have been found to be present at the cell surface of endothelial cells in tumors but not in normal tissues.
n2:mentions
n3:15190345
Subject Item
_:vb7259898
rdf:type
n2:Context
rdf:value
In addition to aforementioned nucleolin, the cytoplasmic proteins annexin1 (Oh et al., 2004) and plectin-1 (Kelly et al., >>2008<<) have been found to be present at the cell surface of endothelial cells in tumors but not in normal tissues.
n2:mentions
n3:18416599
Subject Item
_:vb7259899
rdf:type
n2:Context
rdf:value
This protein is primarily a mitochondrial protein, but it is also expressed at the cell surface of lymphatic, myeloid, and cancer cells in tumors but not in normal tissues (Fogal et al., >>2008<<). This protein is the receptor for the tumor-homing peptide LyP-1, originally discovered using in vivo phage display (Laakkonen et al., 2002).
n2:mentions
n3:18757437
Subject Item
_:vb7259900
rdf:type
n2:Context
rdf:value
This protein is the receptor for the tumor-homing peptide LyP-1, originally discovered using in vivo phage display (Laakkonen et al., >>2002<<).
n2:mentions
n3:12053175
Subject Item
_:vb7259901
rdf:type
n2:Context
rdf:value
A prime example is the overexpression of αvβ3 and αvβ5 integrins in angiogenic vessels (Brooks et al., >>1994<<; Erdreich-Epstein et al., 2000; Desgrosellier and Cheresh, 2010).
n2:mentions
n3:7512751
Subject Item
_:vb7259902
rdf:type
n2:Context
rdf:value
A prime example is the overexpression of αvβ3 and αvβ5 integrins in angiogenic vessels (Brooks et al., 1994; Erdreich-Epstein et al., >>2000<<; Desgrosellier and Cheresh, 2010).
n2:mentions
n3:10676658
Subject Item
_:vb7259903
rdf:type
n2:Context
rdf:value
A prime example is the overexpression of αvβ3 and αvβ5 integrins in angiogenic vessels (Brooks et al., 1994; Erdreich-Epstein et al., 2000; Desgrosellier and Cheresh, >>2010<<). These integrins are prime targets for synaphic drug delivery. Vascular markers expressed on the surface of the endothelium, such as the integrins, are most readily available for the binding of blood-borne compounds. However, the ECM
n2:mentions
n3:20029421
Subject Item
_:vb7259904
rdf:type
n2:Context
rdf:value
An alternatively spliced form of fibronectin containing an additional type III domain, ED-B, is selectively expressed in tumor (and other) angiogenic vessels (Nilsson et al., >>2001<<). Antibodies to ED-B have been used to construct immunotoxins and other compounds for tumor targeting. Proteolytically processed type IV collagen is another matrix component that can be detected with antibodies or peptides (Roth et al.,
n2:mentions
n3:11212273
Subject Item
_:vb7259905
rdf:type
n2:Context
rdf:value
Proteolytically processed type IV collagen is another matrix component that can be detected with antibodies or peptides (Roth et al., >>2006<<; Mueller et al., 2009).
n2:mentions
n3:16651624
Subject Item
_:vb7259906
rdf:type
n2:Context
rdf:value
Proteolytically processed type IV collagen is another matrix component that can be detected with antibodies or peptides (Roth et al., 2006; Mueller et al., >>2009<<). The support cells (mural cells) in the vascular wall also contain markers that are specific for tumor vessels and that can be potentially useful in tumor targeting. NG2, a membrane-spanning chondroitin sulfate proteoglycan, is a cell
n2:mentions
n3:19584266
Subject Item
_:vb7259907
rdf:type
n2:Context
rdf:value
NG2, a membrane-spanning chondroitin sulfate proteoglycan, is a cell surface marker of pericytes (and smooth muscle cells) in angiogenic vessels not expressed in the pericytes of normal vessels (Stallcup and Huang, >>2008<<). One of the PDFG receptors is another marker that is expressed at high levels in pericytes (Song et al., 2005).
n2:mentions
n3:19262111
Subject Item
_:vb7259908
rdf:type
n2:Context
rdf:value
One of the PDFG receptors is another marker that is expressed at high levels in pericytes (Song et al., >>2005<<).
n2:mentions
n3:16113679
Subject Item
_:vb7259909
rdf:type
n2:Context
rdf:value
Leaked fibrinogen is converted to a fibrin meshwork by tissue-procoagulant proteins such as tissue factor (Dvorak et al., >>1985<<; Abe et al., 1999; Pilch et al., 2006).
n2:mentions
n3:3975602
Subject Item
_:vb7259910
rdf:type
n2:Context
rdf:value
Leaked fibrinogen is converted to a fibrin meshwork by tissue-procoagulant proteins such as tissue factor (Dvorak et al., 1985; Abe et al., >>1999<<; Pilch et al., 2006).
n2:mentions
n3:10411932
Subject Item
_:vb7259911
rdf:type
n2:Context
rdf:value
Leaked fibrinogen is converted to a fibrin meshwork by tissue-procoagulant proteins such as tissue factor (Dvorak et al., 1985; Abe et al., 1999; Pilch et al., >>2006<<). Other plasma proteins, plasma fibronectin in particular, become covalently linked or otherwise bound to the fibrin meshwork. These fibrin–fibronectin complexes in the walls of tumor vessels and in the tumor interstitial stroma can be
n2:mentions
n3:16476999
Subject Item
_:vb7259912
rdf:type
n2:Context
rdf:value
These fibrin–fibronectin complexes in the walls of tumor vessels and in the tumor interstitial stroma can be accessed with peptides derived from phage screening, such as the nine–amino acid cyclic peptide CLT-1 (Pilch et al., >>2006<<; Ye et al., 2008) and the pentapeptide CREKA (Simberg et al., 2007). Fibrin-binding peptides isolated for the purpose of targeting blood clots in cardiovascular disease would presumably behave similarly if tested for tumor homing.
n2:mentions
n3:16476999
Subject Item
_:vb7259913
rdf:type
n2:Context
rdf:value
complexes in the walls of tumor vessels and in the tumor interstitial stroma can be accessed with peptides derived from phage screening, such as the nine–amino acid cyclic peptide CLT-1 (Pilch et al., 2006; Ye et al., >>2008<<) and the pentapeptide CREKA (Simberg et al., 2007). Fibrin-binding peptides isolated for the purpose of targeting blood clots in cardiovascular disease would presumably behave similarly if tested for tumor homing.
n2:mentions
n3:19053180
Subject Item
_:vb7259914
rdf:type
n2:Context
rdf:value
and in the tumor interstitial stroma can be accessed with peptides derived from phage screening, such as the nine–amino acid cyclic peptide CLT-1 (Pilch et al., 2006; Ye et al., 2008) and the pentapeptide CREKA (Simberg et al., >>2007<<). Fibrin-binding peptides isolated for the purpose of targeting blood clots in cardiovascular disease would presumably behave similarly if tested for tumor homing.
n2:mentions
n3:17215365
Subject Item
_:vb7259915
rdf:type
n2:Context
rdf:value
The CREKA peptide has been used to confer a new function to nanoparticles: self-amplification of tumor homing (see Amplified tumor homing; Simberg et al., >>2007<<).
n2:mentions
n3:17215365
Subject Item
_:vb7259916
rdf:type
n2:Context
rdf:value
by the serial analysis of gene expression technique has revealed a large number of striking differences between endothelial cells isolated from human colon cancers and those from adjacent normal tissue (Carson-Walter et al., >>2001<<). Among these TEMs are collagens, some of which are expressed at strikingly high levels in tumor endothelial cells, at least at the mRNA level.
n2:mentions
n3:11559528
Subject Item
_:vb7259917
rdf:type
n2:Context
rdf:value
The high collagen expression may relate to the extensive fibrosis found in many tumors and recently shown to contribute to the poor penetration of drugs into tumors (Olive et al., >>2009<<). Perhaps the most interesting among the TEMs is TEM 8, which is one of the two receptors for the anthrax toxin (Nanda et al., 2004). An effort is under way to develop anthrax toxin variants that bind only to TEM 8 and that could be used
n2:mentions
n3:19460966
Subject Item
_:vb7259918
rdf:type
n2:Context
rdf:value
Perhaps the most interesting among the TEMs is TEM 8, which is one of the two receptors for the anthrax toxin (Nanda et al., >>2004<<). An effort is under way to develop anthrax toxin variants that bind only to TEM 8 and that could be used to target tumor vasculature for destruction. Table I provides a list of the principal cell surface markers available in tumor
n2:mentions
n3:14871805
Subject Item
_:vb7259919
rdf:type
n2:Context
rdf:value
ReceptorReferencesRGD-directed integrins (αvβ3 and αvβ5)Ruoslahti, >>2002<<; Desgrosellier and Cheresh, 2010Aminopeptidase NPasqualini et al., 2000TEMsCarson-Walter et al., 2001EndosialinChristian et al., 2001Cell surface nucleolinChristian et al., 2003Cell surface annexin-1Oh et al., 2004Cell surface p32/gC1q
n2:mentions
n3:12635171
Subject Item
_:vb7259920
rdf:type
n2:Context
rdf:value
ReceptorReferencesRGD-directed integrins (αvβ3 and αvβ5)Ruoslahti, 2002; Desgrosellier and Cheresh, >>2010<<Aminopeptidase NPasqualini et al., 2000TEMsCarson-Walter et al., 2001EndosialinChristian et al., 2001Cell surface nucleolinChristian et al., 2003Cell surface annexin-1Oh et al., 2004Cell surface p32/gC1q receptorFogal et al., 2008Cell
n2:mentions
n3:20029421
Subject Item
_:vb7259921
rdf:type
n2:Context
rdf:value
ReceptorReferencesRGD-directed integrins (αvβ3 and αvβ5)Ruoslahti, 2002; Desgrosellier and Cheresh, 2010Aminopeptidase NPasqualini et al., >>2000<<TEMsCarson-Walter et al., 2001EndosialinChristian et al., 2001Cell surface nucleolinChristian et al., 2003Cell surface annexin-1Oh et al., 2004Cell surface p32/gC1q receptorFogal et al., 2008Cell surface plectin-1Kelly et al.,
n2:mentions
n3:10676659
Subject Item
_:vb7259922
rdf:type
n2:Context
rdf:value
ReceptorReferencesRGD-directed integrins (αvβ3 and αvβ5)Ruoslahti, 2002; Desgrosellier and Cheresh, 2010Aminopeptidase NPasqualini et al., 2000TEMsCarson-Walter et al., >>2001<<EndosialinChristian et al., 2001Cell surface nucleolinChristian et al., 2003Cell surface annexin-1Oh et al., 2004Cell surface p32/gC1q receptorFogal et al., 2008Cell surface plectin-1Kelly et al., 2008Fibronectin ED-BNilsson et al.,
n2:mentions
n3:11559528
Subject Item
_:vb7259923
rdf:type
n2:Context
rdf:value
ReceptorReferencesRGD-directed integrins (αvβ3 and αvβ5)Ruoslahti, 2002; Desgrosellier and Cheresh, 2010Aminopeptidase NPasqualini et al., 2000TEMsCarson-Walter et al., 2001EndosialinChristian et al., >>2001<<Cell surface nucleolinChristian et al., 2003Cell surface annexin-1Oh et al., 2004Cell surface p32/gC1q receptorFogal et al., 2008Cell surface plectin-1Kelly et al., 2008Fibronectin ED-BNilsson et al., 2001Fibrin–fibronectin complexesPilch
n2:mentions
n3:11084048
Subject Item
_:vb7259924
rdf:type
n2:Context
rdf:value
integrins (αvβ3 and αvβ5)Ruoslahti, 2002; Desgrosellier and Cheresh, 2010Aminopeptidase NPasqualini et al., 2000TEMsCarson-Walter et al., 2001EndosialinChristian et al., 2001Cell surface nucleolinChristian et al., >>2003<<Cell surface annexin-1Oh et al., 2004Cell surface p32/gC1q receptorFogal et al., 2008Cell surface plectin-1Kelly et al., 2008Fibronectin ED-BNilsson et al., 2001Fibrin–fibronectin complexesPilch et al., 2006; Simberg et al.,
n2:mentions
n3:14638862
Subject Item
_:vb7259925
rdf:type
n2:Context
rdf:value
and αvβ5)Ruoslahti, 2002; Desgrosellier and Cheresh, 2010Aminopeptidase NPasqualini et al., 2000TEMsCarson-Walter et al., 2001EndosialinChristian et al., 2001Cell surface nucleolinChristian et al., 2003Cell surface annexin-1Oh et al., >>2004<<Cell surface p32/gC1q receptorFogal et al., 2008Cell surface plectin-1Kelly et al., 2008Fibronectin ED-BNilsson et al., 2001Fibrin–fibronectin complexesPilch et al., 2006; Simberg et al., 2007Interleukin-11 receptor αLewis et al.,
n2:mentions
n3:15190345
Subject Item
_:vb7259926
rdf:type
n2:Context
rdf:value
2010Aminopeptidase NPasqualini et al., 2000TEMsCarson-Walter et al., 2001EndosialinChristian et al., 2001Cell surface nucleolinChristian et al., 2003Cell surface annexin-1Oh et al., 2004Cell surface p32/gC1q receptorFogal et al., >>2008<<Cell surface plectin-1Kelly et al., 2008Fibronectin ED-BNilsson et al., 2001Fibrin–fibronectin complexesPilch et al., 2006; Simberg et al., 2007Interleukin-11 receptor αLewis et al., 2009Protease-cleaved collagen IVXu et al., 2001; Mueller
n2:mentions
n3:18757437
Subject Item
_:vb7259927
rdf:type
n2:Context
rdf:value
2000TEMsCarson-Walter et al., 2001EndosialinChristian et al., 2001Cell surface nucleolinChristian et al., 2003Cell surface annexin-1Oh et al., 2004Cell surface p32/gC1q receptorFogal et al., 2008Cell surface plectin-1Kelly et al., >>2008<<Fibronectin ED-BNilsson et al., 2001Fibrin–fibronectin complexesPilch et al., 2006; Simberg et al., 2007Interleukin-11 receptor αLewis et al., 2009Protease-cleaved collagen IVXu et al., 2001; Mueller et al., 2009Stage-specific markers.
n2:mentions
n3:18416599
Subject Item
_:vb7259928
rdf:type
n2:Context
rdf:value
et al., 2001Cell surface nucleolinChristian et al., 2003Cell surface annexin-1Oh et al., 2004Cell surface p32/gC1q receptorFogal et al., 2008Cell surface plectin-1Kelly et al., 2008Fibronectin ED-BNilsson et al., >>2001<<Fibrin–fibronectin complexesPilch et al., 2006; Simberg et al., 2007Interleukin-11 receptor αLewis et al., 2009Protease-cleaved collagen IVXu et al., 2001; Mueller et al., 2009Stage-specific markers.
n2:mentions
n3:11212273
Subject Item
_:vb7259929
rdf:type
n2:Context
rdf:value
nucleolinChristian et al., 2003Cell surface annexin-1Oh et al., 2004Cell surface p32/gC1q receptorFogal et al., 2008Cell surface plectin-1Kelly et al., 2008Fibronectin ED-BNilsson et al., 2001Fibrin–fibronectin complexesPilch et al., >>2006<<; Simberg et al., 2007Interleukin-11 receptor αLewis et al., 2009Protease-cleaved collagen IVXu et al., 2001; Mueller et al., 2009Stage-specific markers.
n2:mentions
n3:16476999
Subject Item
_:vb7259930
rdf:type
n2:Context
rdf:value
al., 2003Cell surface annexin-1Oh et al., 2004Cell surface p32/gC1q receptorFogal et al., 2008Cell surface plectin-1Kelly et al., 2008Fibronectin ED-BNilsson et al., 2001Fibrin–fibronectin complexesPilch et al., 2006; Simberg et al., >>2007<<Interleukin-11 receptor αLewis et al., 2009Protease-cleaved collagen IVXu et al., 2001; Mueller et al., 2009Stage-specific markers.
n2:mentions
n3:17215365
Subject Item
_:vb7259931
rdf:type
n2:Context
rdf:value
2004Cell surface p32/gC1q receptorFogal et al., 2008Cell surface plectin-1Kelly et al., 2008Fibronectin ED-BNilsson et al., 2001Fibrin–fibronectin complexesPilch et al., 2006; Simberg et al., 2007Interleukin-11 receptor αLewis et al., >>2009<<Protease-cleaved collagen IVXu et al., 2001; Mueller et al., 2009Stage-specific markers.
n2:mentions
n3:19244100
Subject Item
_:vb7259932
rdf:type
n2:Context
rdf:value
al., 2008Cell surface plectin-1Kelly et al., 2008Fibronectin ED-BNilsson et al., 2001Fibrin–fibronectin complexesPilch et al., 2006; Simberg et al., 2007Interleukin-11 receptor αLewis et al., 2009Protease-cleaved collagen IVXu et al., >>2001<<; Mueller et al., 2009Stage-specific markers.
n2:mentions
n3:11535623
Subject Item
_:vb7259933
rdf:type
n2:Context
rdf:value
plectin-1Kelly et al., 2008Fibronectin ED-BNilsson et al., 2001Fibrin–fibronectin complexesPilch et al., 2006; Simberg et al., 2007Interleukin-11 receptor αLewis et al., 2009Protease-cleaved collagen IVXu et al., 2001; Mueller et al., >>2009<<Stage-specific markers.
n2:mentions
n3:19584266
Subject Item
_:vb7259934
rdf:type
n2:Context
rdf:value
Initiation of angiogenesis (the angiogenic switch) occurs already in premalignant lesions (Hanahan and Folkman, >>1996<<). Peptide probes that distinguish between the blood vessels of premalignant and fully malignant lesions of some de novo cancers in mice have been reported (Hoffman et al., 2003; Joyce et al., 2003). The vascular molecules recognized by
n2:mentions
n3:8756718
Subject Item
_:vb7259935
rdf:type
n2:Context
rdf:value
Peptide probes that distinguish between the blood vessels of premalignant and fully malignant lesions of some de novo cancers in mice have been reported (Hoffman et al., >>2003<<; Joyce et al., 2003).
n2:mentions
n3:14667505
Subject Item
_:vb7259936
rdf:type
n2:Context
rdf:value
Peptide probes that distinguish between the blood vessels of premalignant and fully malignant lesions of some de novo cancers in mice have been reported (Hoffman et al., 2003; Joyce et al., >>2003<<). The vascular molecules recognized by these peptides remain to be identified. It may also be possible to develop targeting probes that distinguish between physiological and tumor angiogenesis (Seaman et al., 2007).
n2:mentions
n3:14667506
Subject Item
_:vb7259937
rdf:type
n2:Context
rdf:value
It may also be possible to develop targeting probes that distinguish between physiological and tumor angiogenesis (Seaman et al., >>2007<<).
n2:mentions
n3:17560335
Subject Item
_:vb7259938
rdf:type
n2:Context
rdf:value
The idea that this level of specificity can be achieved with tumor vessels has been demonstrated with tumor type–specific peptides (Hoffman et al., >>2003<<; Joyce et al., 2003; Laakkonen et al., 2004).
n2:mentions
n3:14667505
Subject Item
_:vb7259939
rdf:type
n2:Context
rdf:value
The idea that this level of specificity can be achieved with tumor vessels has been demonstrated with tumor type–specific peptides (Hoffman et al., 2003; Joyce et al., >>2003<<; Laakkonen et al., 2004).
n2:mentions
n3:14667506
Subject Item
_:vb7259940
rdf:type
n2:Context
rdf:value
The idea that this level of specificity can be achieved with tumor vessels has been demonstrated with tumor type–specific peptides (Hoffman et al., 2003; Joyce et al., 2003; Laakkonen et al., >>2004<<). Peptides like this should make diagnostic and therapeutic applications possible that are more selective than angiogenesis-based targeting. The use of peptides (or other types of probes) with this kind of focused specificity would likely
n2:mentions
n3:15197262
Subject Item
_:vb7259941
rdf:type
n2:Context
rdf:value
The αv integrins play an important role in angiogenesis, although the details of their involvement in this process remain to be fully elucidated (Desgrosellier and Cheresh, >>2010<<). Peptides containing an NGR sequence motif had previously been shown to bind weakly to the RGD-binding site of integrins (Koivunen et al., 1994), but this motif was later identified as the binding motif in tumor-homing peptides that were
n2:mentions
n3:20029421
Subject Item
_:vb7259942
rdf:type
n2:Context
rdf:value
Peptides containing an NGR sequence motif had previously been shown to bind weakly to the RGD-binding site of integrins (Koivunen et al., >>1994<<), but this motif was later identified as the binding motif in tumor-homing peptides that were more potent than could be expected on the basis of the weak integrin binding (Arap et al., 1998).
n2:mentions
n3:7507494
Subject Item
_:vb7259943
rdf:type
n2:Context
rdf:value
site of integrins (Koivunen et al., 1994), but this motif was later identified as the binding motif in tumor-homing peptides that were more potent than could be expected on the basis of the weak integrin binding (Arap et al., >>1998<<). It was subsequently shown that the NGR peptides recognize aminopeptidase N (Pasqualini et al., 2000) and potentially, after a chemical alteration, αv integrins (Curnis et al., 2008).
n2:mentions
n3:9430587
Subject Item
_:vb7259944
rdf:type
n2:Context
rdf:value
It was subsequently shown that the NGR peptides recognize aminopeptidase N (Pasqualini et al., >>2000<<) and potentially, after a chemical alteration, αv integrins (Curnis et al., 2008).
n2:mentions
n3:10676659
Subject Item
_:vb7259945
rdf:type
n2:Context
rdf:value
It was subsequently shown that the NGR peptides recognize aminopeptidase N (Pasqualini et al., 2000) and potentially, after a chemical alteration, αv integrins (Curnis et al., >>2008<<). Like nucleolin, aminopeptidase N is functionally important in the angiogenesis process (Pasqualini et al., 2000; Rangel et al., 2007). These findings serve as a paradigm to illustrate a discovery process in which a new homing peptide is
n2:mentions
n3:18757422
Subject Item
_:vb7259946
rdf:type
n2:Context
rdf:value
Like nucleolin, aminopeptidase N is functionally important in the angiogenesis process (Pasqualini et al., >>2000<<; Rangel et al., 2007).
n2:mentions
n3:10676659
Subject Item
_:vb7259947
rdf:type
n2:Context
rdf:value
Like nucleolin, aminopeptidase N is functionally important in the angiogenesis process (Pasqualini et al., 2000; Rangel et al., >>2007<<). These findings serve as a paradigm to illustrate a discovery process in which a new homing peptide is discovered in phage screening, the receptor for the peptide is identified by biochemical methods such as affinity chromatography, and
n2:mentions
n3:17360568
Subject Item
_:vb7259948
rdf:type
n2:Context
rdf:value
Both F3 and the NGR motif peptides have been used to target drugs to tumors (Curnis et al., >>2004<<; Reddy et al., 2006; Henke et al., 2008), and aptamers that bind nucleolin are being pursued in phase I clinical trials (Laber, D., V.R. Sharma, D.A. Laber, V.R. Sharma, L.
n2:mentions
n3:14744770
Subject Item
_:vb7259949
rdf:type
n2:Context
rdf:value
Both F3 and the NGR motif peptides have been used to target drugs to tumors (Curnis et al., 2004; Reddy et al., >>2006<<; Henke et al., 2008), and aptamers that bind nucleolin are being pursued in phase I clinical trials (Laber, D., V.R. Sharma, D.A. Laber, V.R. Sharma, L.
n2:mentions
n3:17121886
Subject Item
_:vb7259950
rdf:type
n2:Context
rdf:value
Both F3 and the NGR motif peptides have been used to target drugs to tumors (Curnis et al., 2004; Reddy et al., 2006; Henke et al., >>2008<<), and aptamers that bind nucleolin are being pursued in phase I clinical trials (Laber, D., V.R. Sharma, D.A. Laber, V.R. Sharma, L.
n2:mentions
n3:18176556
Subject Item
_:vb7259951
rdf:type
n2:Context
rdf:value
The αvβ3 and αvβ5 integrins are highly expressed in tumor endothelium, and their level of expression may be highest in the vessels of the most malignant tumors (Erdreich-Epstein et al., >>2000<<). Enhanced drug delivery with vascular homing peptides has been accomplished using a cyclic peptide containing the integrin-binding RGD motif (CRGDC) to deliver doxorubicin to tumors (Arap et al., 1998).
n2:mentions
n3:10676658
Subject Item
_:vb7259952
rdf:type
n2:Context
rdf:value
Enhanced drug delivery with vascular homing peptides has been accomplished using a cyclic peptide containing the integrin-binding RGD motif (CRGDC) to deliver doxorubicin to tumors (Arap et al., >>1998<<).
n2:mentions
n3:9430587
Subject Item
_:vb7259953
rdf:type
n2:Context
rdf:value
reported with RGD and NGR peptides; the targeted cytokine was effective in doses as much as 1,000-fold lower than the usual dose and effectively mitigating side effects as a result of the high toxicity of this cytokine (Curnis et al., >>2004<<). These same peptides have also been used to deliver tissue factor to induce blood clotting specifically in tumor blood vessels, with resulting occlusion of the vessels and tumor necrosis (Bieker et al., 2009).
n2:mentions
n3:14744770
Subject Item
_:vb7259954
rdf:type
n2:Context
rdf:value
These same peptides have also been used to deliver tissue factor to induce blood clotting specifically in tumor blood vessels, with resulting occlusion of the vessels and tumor necrosis (Bieker et al., >>2009<<). A targeted TNF is currently in clinical trials (Paoloni et al. 2009; Gregorc et al., 2010).
n2:mentions
n3:19179306
Subject Item
_:vb7259955
rdf:type
n2:Context
rdf:value
A targeted TNF is currently in clinical trials (Paoloni et al. >>2009<<; Gregorc et al., 2010).
n2:mentions
n3:19330034
Subject Item
_:vb7259956
rdf:type
n2:Context
rdf:value
A targeted TNF is currently in clinical trials (Paoloni et al. 2009; Gregorc et al., >>2010<<).
n2:mentions
n3:19900802
Subject Item
_:vb7259957
rdf:type
n2:Context
rdf:value
of an antibacterial peptide, which destroys mitochondria in mammalian cells causing apoptosis, with either the RGD or NGR peptide also inhibited tumor growth in mice, whereas either peptide alone was inactive (Ellerby et al., >>1999<<). Moreover, targeting the same proapoptotic peptide to the blood vessels of the normal prostate caused partial destruction of the prostate and delayed the development of cancers in transgenic prostate cancer mice (Arap et al., 2002).
n2:mentions
n3:10470080
Subject Item
_:vb7259958
rdf:type
n2:Context
rdf:value
Moreover, targeting the same proapoptotic peptide to the blood vessels of the normal prostate caused partial destruction of the prostate and delayed the development of cancers in transgenic prostate cancer mice (Arap et al., >>2002<<). The potential of synaphic targeting is very well illustrated; the combination of homing peptides with nonselectively toxic compounds, such as proapoptotic peptides and TNF, can profoundly alter the in vivo activity of the toxins. RGD
n2:mentions
n3:11830668
Subject Item
_:vb7259959
rdf:type
n2:Context
rdf:value
RGD peptides and antibodies to αvβ3 integrin have also been successfully used in targeted delivery of diagnostic probes to tumors (Sipkins et al., >>1998<<; Stollman et al., 2009; Sugahara et al., 2009), and imaging probes based on this approach are in clinical trials.
n2:mentions
n3:9585240
Subject Item
_:vb7259960
rdf:type
n2:Context
rdf:value
RGD peptides and antibodies to αvβ3 integrin have also been successfully used in targeted delivery of diagnostic probes to tumors (Sipkins et al., 1998; Stollman et al., >>2009<<; Sugahara et al., 2009), and imaging probes based on this approach are in clinical trials.
n2:mentions
n3:19318127
Subject Item
_:vb7259961
rdf:type
n2:Context
rdf:value
RGD peptides and antibodies to αvβ3 integrin have also been successfully used in targeted delivery of diagnostic probes to tumors (Sipkins et al., 1998; Stollman et al., 2009; Sugahara et al., >>2009<<), and imaging probes based on this approach are in clinical trials.
n2:mentions
n3:19962669
Subject Item
_:vb7259962
rdf:type
n2:Context
rdf:value
Drug-loaded nanoparticles have also been targeted with RGD peptides to suppress tumor growth or metastasis (Hood et al., >>2002<<; Murphy et al., 2008; Sugahara et al., 2009).
n2:mentions
n3:12089446
Subject Item
_:vb7259963
rdf:type
n2:Context
rdf:value
Drug-loaded nanoparticles have also been targeted with RGD peptides to suppress tumor growth or metastasis (Hood et al., 2002; Murphy et al., >>2008<<; Sugahara et al., 2009).
n2:mentions
n3:18607000
Subject Item
_:vb7259964
rdf:type
n2:Context
rdf:value
Drug-loaded nanoparticles have also been targeted with RGD peptides to suppress tumor growth or metastasis (Hood et al., 2002; Murphy et al., 2008; Sugahara et al., >>2009<<). Finally, RGD and other tumor-homing peptides have been used to alter the host range of viral gene therapy vectors (Wickham, 2000; Haviv et al., 2002). Several homing peptides that bind to receptors other than integrins have also been
n2:mentions
n3:19962669
Subject Item
_:vb7259965
rdf:type
n2:Context
rdf:value
Finally, RGD and other tumor-homing peptides have been used to alter the host range of viral gene therapy vectors (Wickham, >>2000<<; Haviv et al., 2002).
n2:mentions
n3:10673715
Subject Item
_:vb7259966
rdf:type
n2:Context
rdf:value
Finally, RGD and other tumor-homing peptides have been used to alter the host range of viral gene therapy vectors (Wickham, 2000; Haviv et al., >>2002<<). Several homing peptides that bind to receptors other than integrins have also been successfully used in preclinical studies to target gene therapy vectors, drugs, and biologicals into tumors (Müller et al., 2003; Hamzah et al., 2008;
n2:mentions
n3:12154029
Subject Item
_:vb7259967
rdf:type
n2:Context
rdf:value
Several homing peptides that bind to receptors other than integrins have also been successfully used in preclinical studies to target gene therapy vectors, drugs, and biologicals into tumors (Müller et al., >>2003<<; Hamzah et al., 2008; Chang et al., 2009; Karmali et al., 2009).
n2:mentions
n3:12897791
Subject Item
_:vb7259968
rdf:type
n2:Context
rdf:value
Several homing peptides that bind to receptors other than integrins have also been successfully used in preclinical studies to target gene therapy vectors, drugs, and biologicals into tumors (Müller et al., 2003; Hamzah et al., >>2008<<; Chang et al., 2009; Karmali et al., 2009).
n2:mentions
n3:18398504
Subject Item
_:vb7259969
rdf:type
n2:Context
rdf:value
peptides that bind to receptors other than integrins have also been successfully used in preclinical studies to target gene therapy vectors, drugs, and biologicals into tumors (Müller et al., 2003; Hamzah et al., 2008; Chang et al., >>2009<<; Karmali et al., 2009).
n2:mentions
n3:19276080
Subject Item
_:vb7259970
rdf:type
n2:Context
rdf:value
receptors other than integrins have also been successfully used in preclinical studies to target gene therapy vectors, drugs, and biologicals into tumors (Müller et al., 2003; Hamzah et al., 2008; Chang et al., 2009; Karmali et al., >>2009<<).
n2:mentions
n3:18829396
Subject Item
_:vb7259971
rdf:type
n2:Context
rdf:value
This problem is particularly prominent with solid tumors, which have a high interstitial pressure, presumably because their blood vessels tend to be leaky and their lymphatic vessels poorly functional (Jain, >>1999<<). Drugs generally do not penetrate further than three to five cell diameters from blood vessels, which leaves more distantly located tumor cells without any drug or exposes them to low drug concentrations that are likely to facilitate the
n2:mentions
n3:11701489
Subject Item
_:vb7259972
rdf:type
n2:Context
rdf:value
to five cell diameters from blood vessels, which leaves more distantly located tumor cells without any drug or exposes them to low drug concentrations that are likely to facilitate the development of resistance (Hambley and Hait, >>2009<<). Despite these limitations, a homing peptide that binds to the Her2 receptor (Gee et al., 2008) has been used to deliver compounds to tumors that overexpress this receptor.
n2:mentions
n3:19208831
Subject Item
_:vb7259973
rdf:type
n2:Context
rdf:value
Despite these limitations, a homing peptide that binds to the Her2 receptor (Gee et al., >>2008<<) has been used to deliver compounds to tumors that overexpress this receptor.
n2:mentions
n3:18647846
Subject Item
_:vb7259974
rdf:type
n2:Context
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Folic acid is another probe commonly used to target the folate receptor, which is overexpressed by tumor cells in many tumors (for review see Salazar and Ratnam, >>2007<<). Experimental and theoretical results indicate that this increase in efficacy is not dominated by changes in overall drug uptake by the tumor (i.e., increased volumetric concentration) but rather changes in cellular internalization of
n2:mentions
n3:17333345
Subject Item
_:vb7259975
rdf:type
n2:Context
rdf:value
efficacy is not dominated by changes in overall drug uptake by the tumor (i.e., increased volumetric concentration) but rather changes in cellular internalization of the drug or how long it is retained in the tumor (Bartlett et al., >>2007<<). Thus, there is little or no specific accumulation of probes targeted solely to tumor cells (Fig.
n2:mentions
n3:17875985
Subject Item
_:vb7259976
rdf:type
n2:Context
rdf:value
The peptides contain a tissue penetration motif, R/KXXR/K, which has to be exposed at the C terminus of a peptide (or protein) to be active (the C-end rule [CendR]; Teesalu et al., >>2009<<). A tumor-homing CendR peptide contains both a tumor-specific homing sequence and a cryptic (not C terminal) CendR sequence. The homing sequence takes the peptide to the vascular endothelium in the target tissue, where the peptide is
n2:mentions
n3:19805273
Subject Item
_:vb7259977
rdf:type
n2:Context
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The iRGD peptide penetrates into tumor tissue and is capable of carrying 10 times more drug cargo into a tumor than a conventional RGD peptide (Sugahara et al., >>2009<<).
n2:mentions
n3:19962669
Subject Item
_:vb7259978
rdf:type
n2:Context
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F3 (Porkka et al., >>2002<<), LyP-1 (Laakkonen et al., 2002), and CRGRRST (Joyce et al., 2003) each contain a potential CendR sequence.
n2:mentions
n3:12032302
Subject Item
_:vb7259979
rdf:type
n2:Context
rdf:value
F3 (Porkka et al., 2002), LyP-1 (Laakkonen et al., >>2002<<), and CRGRRST (Joyce et al., 2003) each contain a potential CendR sequence.
n2:mentions
n3:12053175
Subject Item
_:vb7259980
rdf:type
n2:Context
rdf:value
F3 (Porkka et al., 2002), LyP-1 (Laakkonen et al., 2002), and CRGRRST (Joyce et al., >>2003<<) each contain a potential CendR sequence.
n2:mentions
n3:14667506
Subject Item
_:vb7259981
rdf:type
n2:Context
rdf:value
Moreover, F3 and LyP-1 have been shown to cause extravasation of their cargo, which can be as large as a nanoparticle, with subsequent uptake into tumor endothelial cells and tumor cells (Porkka et al., >>2002<<; Laakkonen et al., 2004; Karmali et al., 2009).
n2:mentions
n3:12032302
Subject Item
_:vb7259982
rdf:type
n2:Context
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Moreover, F3 and LyP-1 have been shown to cause extravasation of their cargo, which can be as large as a nanoparticle, with subsequent uptake into tumor endothelial cells and tumor cells (Porkka et al., 2002; Laakkonen et al., >>2004<<; Karmali et al., 2009).
n2:mentions
n3:15197262
Subject Item
_:vb7259983
rdf:type
n2:Context
rdf:value
LyP-1 have been shown to cause extravasation of their cargo, which can be as large as a nanoparticle, with subsequent uptake into tumor endothelial cells and tumor cells (Porkka et al., 2002; Laakkonen et al., 2004; Karmali et al., >>2009<<). Coating of abraxane, which is a nanoparticle drug composed of paclitaxel and albumin, with the LyP-1 or iRGD peptide made the drug capable of penetrating into tumor tissue, resulting in several-fold higher activity than that of the
n2:mentions
n3:18829396
Subject Item
_:vb7259984
rdf:type
n2:Context
rdf:value
a nanoparticle drug composed of paclitaxel and albumin, with the LyP-1 or iRGD peptide made the drug capable of penetrating into tumor tissue, resulting in several-fold higher activity than that of the original drug (Karmali et al., >>2009<<; Sugahara et al., 2009).
n2:mentions
n3:18829396
Subject Item
_:vb7259985
rdf:type
n2:Context
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of paclitaxel and albumin, with the LyP-1 or iRGD peptide made the drug capable of penetrating into tumor tissue, resulting in several-fold higher activity than that of the original drug (Karmali et al., 2009; Sugahara et al., >>2009<<). The tissue-penetrating properties of these peptides and their internalization into cells makes them particularly efficient in achieving a high concentration of the peptide and any payload attached to it in tumor tissue.
n2:mentions
n3:19962669
Subject Item
_:vb7259986
rdf:type
n2:Context
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Unlike the cell-penetrating peptides related to the human immunodeficiency virus Tat protein, which do not display any cell type specificity (Gump and Dowdy, >>2007<<), the CendR tumor-homing peptides are tumor specific.
n2:mentions
n3:17913584
Subject Item
_:vb7259987
rdf:type
n2:Context
rdf:value
Jiang et al. (>>2004<<) have described a peptide design in which a negatively charged sequence tethered to a cationic cell-penetrating peptide blocks the cell-penetrating activity until a tumor protease cleaves the tether.
n2:mentions
n3:15601762
Subject Item
_:vb7259988
rdf:type
n2:Context
rdf:value
The greater tumor-homing selectivity of peptides derived from in vivo phage display such as iRGD (12-fold) is likely because of the presence of a homing sequence (RGD in iRGD) in these peptides (Sugahara et al., >>2009<<).
n2:mentions
n3:19962669
Subject Item
_:vb7259989
rdf:type
n2:Context
rdf:value
One potential solution to this problem is to use higher affinity ligands for the targeting, but this strong binding can lead to reduced tumor penetration through the so-called binding site barrier (van Osdol et al., >>1991<<; Thurber et al., 2008).
n2:mentions
n3:1893370
Subject Item
_:vb7259990
rdf:type
n2:Context
rdf:value
potential solution to this problem is to use higher affinity ligands for the targeting, but this strong binding can lead to reduced tumor penetration through the so-called binding site barrier (van Osdol et al., 1991; Thurber et al., >>2008<<). Other potential solutions include using anticancer agents with higher potency than most current drugs, using nanoparticle delivery vehicles that deliver more drug per receptor occupied than one to one conjugates, or inducing more
n2:mentions
n3:18541331
Subject Item
_:vb7259991
rdf:type
n2:Context
rdf:value
Once the receptors of the homing peptide have been saturated, the specificity of the targeting declines (adapted from experimental data in Kranenborg et al., >>1998<<). au, arbitrary units.
n2:mentions
n3:9426693
Subject Item
_:vb7259992
rdf:type
n2:Context
rdf:value
Phage display with cells in vitro or tissues in vivo as the target (Hoffman et al., >>2003<<) is a prime example of a system that probes this moderate affinity, multivalent landscape.
n2:mentions
n3:14667505
Subject Item
_:vb7259993
rdf:type
n2:Context
rdf:value
Thus, phage display complements other target discovery methods such as those based on antibodies (Jacobson et al., >>1996<<; Oh et al., 2004) or cloning methods (Seaman et al., 2007).
n2:mentions
n3:8597963
Subject Item
_:vb7259994
rdf:type
n2:Context
rdf:value
Thus, phage display complements other target discovery methods such as those based on antibodies (Jacobson et al., 1996; Oh et al., >>2004<<) or cloning methods (Seaman et al., 2007).
n2:mentions
n3:15190345
Subject Item
_:vb7259995
rdf:type
n2:Context
rdf:value
Thus, phage display complements other target discovery methods such as those based on antibodies (Jacobson et al., 1996; Oh et al., 2004) or cloning methods (Seaman et al., >>2007<<). The enhanced avidity from multivalency is usually the result of an unaffected binding rate (on rate [kon]) but a reduction in off rate (koff) for the multiple interactions. Multivalency is important in nanoparticle-based targeting
n2:mentions
n3:17560335
Subject Item
_:vb7259996
rdf:type
n2:Context
rdf:value
Reulen et al. (>>2009<<) converted a nonbinding variant of a collagen-binding protein into an active targeting probe by inserting multiple copies of the protein into a micelle, artificially producing a multivalent ensemble.
n2:mentions
n3:19469576
Subject Item
_:vb7259997
rdf:type
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rdf:value
enhancement in dendrimer binding to a surface (dendrimers are branched synthetic polymers that can form nanoparticles and present ligands in a multivalent fashion in which the valency can be readily controlled; Montet et al., >>2006<<; Hong et al., 2007). At the same time, multivalent peptide presentation can increase recognition of nanoparticles by the reticuloendothelial system (RES; also known as the mononuclear phagocyte system [MPS]).
n2:mentions
n3:17004722
Subject Item
_:vb7259998
rdf:type
n2:Context
rdf:value
in dendrimer binding to a surface (dendrimers are branched synthetic polymers that can form nanoparticles and present ligands in a multivalent fashion in which the valency can be readily controlled; Montet et al., 2006; Hong et al., >>2007<<). At the same time, multivalent peptide presentation can increase recognition of nanoparticles by the reticuloendothelial system (RES; also known as the mononuclear phagocyte system [MPS]).
n2:mentions
n3:17254956
Subject Item
_:vb7259999
rdf:type
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rdf:value
Multivalency may partially explain the remarkable 1,000-fold increase in the antitumor activity of TNF observed when homing peptides recognizing tumor vessels were added to the protein (Curnis et al., >>2004<<). TNF is a trimeric protein, which would render the homing peptide multivalent.
n2:mentions
n3:14744770
Subject Item
_:vb7260000
rdf:type
n2:Context
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Long circulation times are especially important when the target is outside the vasculature, although tumor-penetrating peptides offer a potential solution to this problem (Sugahara et al., >>2009<<). The half-life primarily depends on the rate of elimination into the urine (small molecules) and uptake by the RES in the liver and spleen (particles). Coupling a small molecular mass drug or probe to polyethylene glycol is commonly used
n2:mentions
n3:19962669
Subject Item
_:vb7260001
rdf:type
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rdf:value
Coupling a small molecular mass drug or probe to polyethylene glycol is commonly used to increase molecular mass above the kidney filtration cut-off size of 5 nm (Choi et al., >>2007<<). Polyethylene glycol coating is also a strategy used to minimize elimination of protein therapeutics. Preventing RES uptake is particularly important when nanoparticles are used in drug delivery.
n2:mentions
n3:17891134
Subject Item
_:vb7260002
rdf:type
n2:Context
rdf:value
Tumor-responsive, cleavable stealth coatings have been used to mitigate this problem (Harris et al., >>2008<<), but the RES/MPS uptake of nanoparticles remains a major problem in the use of nanoparticles in nanomedicine.
n2:mentions
n3:18690639
Subject Item
_:vb7260003
rdf:type
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rdf:value
Kupffer cell receptors in the liver is thought to underlie this phenomenon, but the unfortunate fact is that the molecular mechanisms of the uptake of nanoparticles by the RES are not really understood (for review see Moghimi et al., >>2001<<). It has been empirically shown that particle charge (anionic or neutral), size (<100 nm), and ability to prevent complement binding can reduce rates of RES uptake and extend circulation time in mice (for review see Peer et al., 2007).
n2:mentions
n3:11356986
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_:vb7260004
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It has been empirically shown that particle charge (anionic or neutral), size (<100 nm), and ability to prevent complement binding can reduce rates of RES uptake and extend circulation time in mice (for review see Peer et al., >>2007<<). Other results suggest that the RES uptake may have little to do with plasma protein–mediated opsonization (Simberg et al., 2009). The likely explanation for why this has been such an intractable problem is that the Kupffer cell
n2:mentions
n3:18654426
Subject Item
_:vb7260005
rdf:type
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rdf:value
Other results suggest that the RES uptake may have little to do with plasma protein–mediated opsonization (Simberg et al., >>2009<<). The likely explanation for why this has been such an intractable problem is that the Kupffer cell receptors use multiple low affinity interactions to capture nano (and micro)-particles, rendering conventional receptor identification
n2:mentions
n3:19394687
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_:vb7260006
rdf:type
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Iron oxide nanoparticles coated with the CREKA peptide bind and accumulate in tumor vessels where they cause additional clotting (Simberg et al., >>2007<<). The approach is similar to clotting induced in tumor vessels by tumor-targeted tissue factor (Huang et al., 1997; Bieker et al., 2009) with the exception that the CREKA system is based on self-amplified nanoparticle homing. The clotting
n2:mentions
n3:17215365
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_:vb7260007
rdf:type
n2:Context
rdf:value
The approach is similar to clotting induced in tumor vessels by tumor-targeted tissue factor (Huang et al., >>1997<<; Bieker et al., 2009) with the exception that the CREKA system is based on self-amplified nanoparticle homing.
n2:mentions
n3:8999802
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_:vb7260008
rdf:type
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The approach is similar to clotting induced in tumor vessels by tumor-targeted tissue factor (Huang et al., 1997; Bieker et al., >>2009<<) with the exception that the CREKA system is based on self-amplified nanoparticle homing.
n2:mentions
n3:19179306
Subject Item
_:vb7260009
rdf:type
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These materials are metallic structures that efficiently convert optical radiation into heat by coupling into one or more plasmon modes (Hirsch et al., >>2003<<; Hu et al., 2006).
n2:mentions
n3:14597719
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_:vb7260010
rdf:type
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These materials are metallic structures that efficiently convert optical radiation into heat by coupling into one or more plasmon modes (Hirsch et al., 2003; Hu et al., >>2006<<). We have recently shown that photothermal heating mediated by tumor-targeted gold nanorods can increase binding sites for targeted delivery with thermosensitive drug carriers (Fig. 3; von Maltzahn et al., 2009; Park et al., 2010). Other
n2:mentions
n3:17057837
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_:vb7260011
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3; von Maltzahn et al., >>2009<<; Park et al., 2010). Other biological cascades, such as the protease activity that activates CendR peptides in tumors (Sugahara et al., 2009), can be exploited.
n2:mentions
n3:20174478
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_:vb7260012
rdf:type
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3; von Maltzahn et al., 2009; Park et al., >>2010<<). Other biological cascades, such as the protease activity that activates CendR peptides in tumors (Sugahara et al., 2009), can be exploited.
n2:mentions
n3:20080556
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_:vb7260013
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Other biological cascades, such as the protease activity that activates CendR peptides in tumors (Sugahara et al., >>2009<<), can be exploited.
n2:mentions
n3:19962669
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to guide the surgical procedure (by magnetic resonance imaging) and a high resolution mapping that can be visualized during surgery to identify surgical margins (by fluorescence imaging of quantum dots; Wang et al., 2004; Kim et al., >>2005<<; Sathe et al., 2006; Kim and Taton, 2007; Song et al., 2007; Park et al., 2008; Ye et al., 2008).
n2:mentions
n3:15643877
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procedure (by magnetic resonance imaging) and a high resolution mapping that can be visualized during surgery to identify surgical margins (by fluorescence imaging of quantum dots; Wang et al., 2004; Kim et al., 2005; Sathe et al., >>2006<<; Kim and Taton, 2007; Song et al., 2007; Park et al., 2008; Ye et al., 2008).
n2:mentions
n3:16906704
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_:vb7260016
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resonance imaging) and a high resolution mapping that can be visualized during surgery to identify surgical margins (by fluorescence imaging of quantum dots; Wang et al., 2004; Kim et al., 2005; Sathe et al., 2006; Kim and Taton, >>2007<<; Song et al., 2007; Park et al., 2008; Ye et al., 2008).
n2:mentions
n3:17279714
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_:vb7260017
rdf:type
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and a high resolution mapping that can be visualized during surgery to identify surgical margins (by fluorescence imaging of quantum dots; Wang et al., 2004; Kim et al., 2005; Sathe et al., 2006; Kim and Taton, 2007; Song et al., >>2007<<; Park et al., 2008; Ye et al., 2008). Recently, we have also designed iron oxide nanoparticles (nanoworms; Park et al., 2009b) with improved properties and nontoxic silicon-based quantum dots (Park et al., 2009a) for such purposes.
n2:mentions
n3:17962366
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_:vb7260018
rdf:type
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mapping that can be visualized during surgery to identify surgical margins (by fluorescence imaging of quantum dots; Wang et al., 2004; Kim et al., 2005; Sathe et al., 2006; Kim and Taton, 2007; Song et al., 2007; Park et al., >>2008<<; Ye et al., 2008). Recently, we have also designed iron oxide nanoparticles (nanoworms; Park et al., 2009b) with improved properties and nontoxic silicon-based quantum dots (Park et al., 2009a) for such purposes.
n2:mentions
n3:18696519
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_:vb7260019
rdf:type
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can be visualized during surgery to identify surgical margins (by fluorescence imaging of quantum dots; Wang et al., 2004; Kim et al., 2005; Sathe et al., 2006; Kim and Taton, 2007; Song et al., 2007; Park et al., 2008; Ye et al., >>2008<<). Recently, we have also designed iron oxide nanoparticles (nanoworms; Park et al., 2009b) with improved properties and nontoxic silicon-based quantum dots (Park et al., 2009a) for such purposes.
n2:mentions
n3:19053180
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Recently, we have also designed iron oxide nanoparticles (nanoworms; Park et al., 2009b) with improved properties and nontoxic silicon-based quantum dots (Park et al., 2009a) for such purposes.
n2:mentions
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