Peptides selected for binding to clotted plasma accumulate in tumor stroma and wounds

Pilch, Ján; Brown, Darren M.; Komatsu, Masanobu; Järvinen, Tero A.H.; Yang, Meng; Peters, David G.; Hoffman, Robert M.; Ruoslahti, Erkki

doi:10.1073/pnas.0511219103

Cited by 143 publications

(123 citation statements)

References 28 publications

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“…In another example, a strategy for selecting T7 phage library members that bound to plasma clots, but not to liquid plasma components, identified two cyclic peptides: CGLIIQKNEC (CLT1) and CNAGESSKNC (CLT2) (Pilch et al 2006). Studies in mice strongly indicated that these peptides recognize fibrin-fibrinogen complexes formed by clotting plasma proteins that leaked into the extravascular space in tumors and other lesions.…”

Section: Molecular Imaging Agents Obtained Using Intact Cells and Ex mentioning

confidence: 99%

Phage display and molecular imaging: expanding fields of vision in living subjects

Cochran

2010

Biotechnology and Genetic Engineering Reviews

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In vivo molecular imaging enables non-invasive visualization of biological processes within living subjects, and holds great promise for diagnosis and monitoring of disease. The ability to create new agents that bind to molecular targets and deliver imaging probes to desired locations in the body is critically important to further advance this field. To address this need, phage display, an established technology for the discovery and development of novel binding agents, is increasingly becoming a key component of many molecular imaging research programs. This review discusses the expanding role played by phage display in the field of molecular imaging with a focus on in vivo applications. Furthermore, new methodological advances in phage display that can be directly applied to the discovery and development of molecular imaging agents are described. Various phage library selection strategies are summarized and compared, including selections against purified target, intact cells, and ex vivo tissue, plus in vivo homing strategies. An outline of the process for converting polypeptides obtained from phage display library selections into successful in vivo imaging agents is provided, including strategies to optimize in vivo performance. Additionally, the use To whom correspondence may be addressed (cochran1@stanford.edu) Abbreviations: scFv, single chain variable fragment; Fab, fragment antigen binding; ELISA, Enzyme-Linked Immunosorbent Assay; NEB, New England Biolabs; PET, positron emission tomography; SPECT, single photon emission computed tomography; NIR, near infrared; PEG, polyethylene glycol; SPARC, secreted protein acidic and rich in cysteine; VCAM-1, vascular cell adhesion molecule; MRI, magnetic resonance imaging; DOTA, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; IC 50 , half maximal inhibitory concentration; CT, computed tomography; K D , equilibrium dissociation constant; EGFR, epidermal growth factor receptor; EGFR-ECD, EGFR extracellular domain; Aβ 42 , amyloid-beta; MMP, matrix metalloprotease; uPAR, urokinase-type plasminogen activator receptor; VEGF, vascular endothelial growth factor; IL-11, Interleukin-11; IL-11αR, Interleukin-11 α-receptor. 58F.V. CoChran and J.r. CoChran of phage particles as imaging agents is also described. In the latter part of the review, a survey of phage-derived in vivo imaging agents is presented, and important recent examples are highlighted. Other imaging applications are also discussed, such as the development of peptide tags for site-specific protein labeling and the use of phage as delivery agents for reporter genes. The review concludes with a discussion of how phage display technology will continue to impact both basic science and clinical applications in the field of molecular imaging.

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Section: Molecular Imaging Agents Obtained Using Intact Cells and Ex mentioning

confidence: 99%

Phage display and molecular imaging: expanding fields of vision in living subjects

Cochran

2010

Biotechnology and Genetic Engineering Reviews

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“…Tumors contain a meshwork of clotted plasma proteins in the tumor stroma and the walls of vessels, but no such meshwork is detectable in normal tissues (13)(14)(15). The mesh-like pattern produced by the CREKA peptide in tumors prompted us to study whether clotted plasma proteins might be the target of this peptide.…”

Section: Creka Peptidementioning

confidence: 99%

Biomimetic amplification of nanoparticle homing to tumors

Simberg

Duza

Park

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Nanoparticle-based diagnostics and therapeutics hold great promise because multiple functions can be built into the particles. One such function is an ability to home to specific sites in the body. We describe here biomimetic particles that not only home to tumors, but also amplify their own homing. The system is based on a peptide that recognizes clotted plasma proteins and selectively homes to tumors, where it binds to vessel walls and tumor stroma. Iron oxide nanoparticles and liposomes coated with this tumorhoming peptide accumulate in tumor vessels, where they induce additional local clotting, thereby producing new binding sites for more particles. The system mimics platelets, which also circulate freely but accumulate at a diseased site and amplify their own accumulation at that site. The self-amplifying homing is a novel function for nanoparticles. The clotting-based amplification greatly enhances tumor imaging, and the addition of a drug carrier function to the particles is envisioned.clotting ͉ liver ͉ peptide ͉ tumor targeting ͉ iron oxide

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“…19,20 We have identified 3 tumor-homing peptides that recognize these clotting products in the vessels of a variety of tumor types, including human cancers. 21,22 Tumors grown in mutant mice null for fibrinogen or in mice lacking plasma fibronectin, which becomes covalently bound to fibrin during blood clotting, are not recognized by these peptides, which indicates that the peptides target fibrin-fibronectin complexes.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle-induced vascular blockade in human prostate cancer

Agemy

Sugahara

Kotamraju

et al. 2010

Blood

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153

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The tumor-homing pentapeptide CREKA (Cys-Arg-Glu-Lys-Ala) specifically homes to tumors by binding to fibrin and fibrinassociated clotted plasma proteins in tumor vessels. Previous results show that CREKA-coated superparamagnetic iron oxide particles can cause additional clotting in tumor vessels, which creates more binding sites for the peptide. We have used this self-amplifying homing system to develop theranostic nanoparticles that simultaneously serve as an imaging agent and inhibit tumor growth by obstructing tumor circulation through blood clotting. The CREKA nanoparticles were combined with nanoparticles coated with another tumor-homing peptide, CRKDKC, and nanoparticles with an elongated shape (nanoworms) were used for improved binding efficacy. The efficacy of the CREKA peptide was then increased by replacing some residues with nonproteinogenic counterparts, which increased the stability of the peptide in the circula-

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Peptides selected for binding to clotted plasma accumulate in tumor stroma and wounds

Cited by 143 publications

References 28 publications

Phage display and molecular imaging: expanding fields of vision in living subjects

Phage display and molecular imaging: expanding fields of vision in living subjects

Biomimetic amplification of nanoparticle homing to tumors

Nanoparticle-induced vascular blockade in human prostate cancer

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