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Open Access item Nanoparticle-induced vascular blockade in human prostate cancer

Authors:Agemy, Lilach
Jiménez, Ana I.
Cativiela, Carlos
Zanuy, David
Alemán, Carlos
Nussinov, Ruth
Issue Date:Oct-2010
Publisher:American Society of Hematology
Citation:Blood 116(15): 2847-2856 (2010)
Abstract: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 circulation. Treatment of mice bearing orthotopic human prostate cancer tumors with the targeted nanoworms caused extensive clotting in tumor vessels, whereas no clotting was observed in the vessels of normal tissues. Optical and magnetic resonance imaging confirmed tumorspecific targeting of the nanoworms, and ultrasound imaging showed reduced blood flow in tumor vessels. Treatment of mice with prostate cancer with multiple doses of the nanoworms induced tumor necrosis and a highly significant reduction in tumor growth.
Description:10 páginas, 7 figuras.-- El pdf del artículo es la versión post-print.-- et al.
Publisher version (URL):http://dx.doi.org/10.1182/blood-2010-03-274258
URI:http://hdl.handle.net/10261/47691
ISSN:0006-4971
E-ISSNmetadata.dc.identifier.doi = DOI:1528-0020
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