title: VCAM-1-targeted core/shell nanoparticles for selective adhesion and delivery to endothelial cells with lipopolysaccharide-induced inflammation under shear flow and cellular magnetic resonance imaging in vitro.
abstract: Multifunctional nanomaterials with unique magnetic and luminescent properties have broad potential in biological applications. Because of the overexpression of vascular cell adhesion molecule-1 (VCAM-1) receptors in inflammatory endothelial cells as compared with normal endothelial cells, an anti-VCAM-1 monoclonal antibody can be used as a targeting ligand. Herein we describe the development of multifunctional core-shell Fe(3)O(4)@SiO2 nanoparticles with the ability to target inflammatory endothelial cells via VCAM-1, magnetism, and fluorescence imaging, with efficient magnetic resonance imaging contrast characteristics. Superparamagnetic iron oxide and fluorescein isothiocyanate (FITC) were loaded successfully inside the nanoparticle core and the silica shell, respectively, creating VCAM-1-targeted Fe(3)O(4)@SiO2(FITC) nanoparticles that were characterized by scanning electron microscopy, transmission electron microscopy, fluorescence spectrometry, zeta potential assay, and fluorescence microscopy. The VCAM-1-targeted Fe(3)O(4)@SiO2(FITC) nanoparticles typically had a diameter of 355 ± 37 nm, showed superparamagnetic behavior at room temperature, and cumulative and targeted adhesion to an inflammatory subline of human umbilical vein endothelial cells (HUVEC-CS) activated by lipopolysaccharide. Further, our data show that adhesion of VCAM-1-targeted Fe(3)O(4)@SiO2(FITC) nanoparticles to inflammatory HUVEC-CS depended on both shear stress and duration of exposure to stress. Analysis of internalization into HUVEC-CS showed that the efficiency of delivery of VCAM-1-targeted Fe(3)O(4)@SiO2(FITC) nanoparticles was also significantly greater than that of nontargeted Fe(3)O(4)@SiO2(FITC)-NH2 nanoparticles. Magnetic resonance images showed that the superparamagnetic iron oxide cores of the VCAM-1-targeted Fe(3)O(4)@SiO2(FITC) nanoparticles could also act as a contrast agent for magnetic resonance imaging. Taken together, the cumulative adhesion and uptake potential of these VCAM-1-targeted Fe(3)O(4)@SiO2(FITC) nanoparticles targeted to inflammatory endothelial cells could be used in the transfer of therapeutic drugs/genes into these cells or for diagnosis of vascular disease at the molecular and cellular levels in the future.
authors.affiliation: Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Fenglong
authors.initials: F
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Mingming
authors.initials: M
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Chunhui
authors.initials: C
authors.lastname: Wu
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Yiyao
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D012822:Silicon Dioxide; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D008070:Lipopolysaccharides; D058185:Magnetite Nanoparticles; D019010:Vascular Cell Adhesion Molecule-1; D012822:Silicon Dioxide
keywords: adhesion; endothelial cells; magnetic resonance imaging; silica nanoparticles; vascular cell adhesion molecule-1