title: Multifunctional polyurethane-urea nanoparticles to target and arrest inflamed vascular environment: a potential tool for cancer therapy and diagnosis.
abstract: Activation of inflammatory pathways in endothelial cells contributes to tumour growth and progression in multiple human cancers. Cellular adhesion molecules are involved in leukocyte recruitment to the vascular inflammatory environment where it plays a critical role in angiogenesis, suppression of apoptosis, proliferation, invasion and metastasis. We describe here the development of streptavidin-coated polyurethane-urea nanoparticles as multifunctional nanocarriers for fluorescence imaging or targeting of the tumour environment to identify and arrest the vascular network irrigating the tumour tissue. The design of these multifunctional nanoparticles involves incorporating streptavidin to the nanoparticle polymeric matrix. The obtained nanoparticles are spherical and exhibit an average diameter of 70-74 nm. Streptavidin-coated nanoparticles spontaneously bind biotinylated antibodies against VCAM-1 and ICAM-1 which in vitro and in vivo specifically attached to inflamed endothelial cells. Indeed the incorporation of CBO-P11 (a specific inhibitor of the vascular endothelial growth factor proangiogenic and proinflammatory pathway) to these nanoparticles allows a targeted pharmacological effect thereby decreasing the proliferation only in inflamed endothelial cells. The multiple functionalisation strategy described here could be exploited for tumour diagnostics or targeted drug delivery to tumour vasculature with a good safety profile and an attractive array of possibilities for biomedical applications.
authors.affiliation: Departament de Farmàcia i Tecnologia Farmacèutica, Unitat R&D associada al CSIC, Facultat de Farmàcia, Universitat de Barcelona, Av Joan XXIII s/n, 08028 Barcelona, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Morral-Ruíz
authors.forename: P
authors.initials: P
authors.lastname: Melgar-Lesmes
authors.forename: C
authors.initials: C
authors.lastname: Solans
authors.forename: M J
authors.initials: MJ
authors.lastname: García-Celma
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001710:Biotin / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D016228:Endothelial Growth Factors / Q000008:administration & dosage* / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008070:Lipopolysaccharides; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000098:blood supply / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000188:drug therapy*; D010456:Peptides, Cyclic / Q000008:administration & dosage* / Q000737:chemistry; D011140:Polyurethanes / Q000737:chemistry; D019809:Streptavidin / Q000737:chemistry; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D000906:Antibodies; D004337:Drug Carriers; D016228:Endothelial Growth Factors; D008070:Lipopolysaccharides; D010456:Peptides, Cyclic; D011140:Polyurethanes; D019010:Vascular Cell Adhesion Molecule-1; C478485:cyclo-VEGI; D018799:Intercellular Adhesion Molecule-1; D001710:Biotin; D019809:Streptavidin; C044690:polyetherurethane urea; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Angiogenesis; Cell proliferation; Inflammation; Nanoparticle; Polyurethane; Targeting