Polyethylene glycol–coated gold nanoshells conjugated with anti-VCAM-1 antibody

摘要: Optical fluorescence imaging is increasingly used to monitor biological functions of specific targets in small animals (1-3). However, the intrinsic biomolecules poses a problem when fluorophores that absorb visible light (350–650 nm) are used. Near-infrared (NIR) (650–1,000 detection avoids background interference natural biomolecules, providing high contrast between target and tissues. NIR have wider dynamic range minimal as result reduced scattering compared with detection. They also sensitivity, resulting from low infrared background, extinction coefficients, which provide quantum yields. The region compatible solid-state optical components, such diode lasers silicon detectors. becoming noninvasive alternative radionuclide (4, 5).Photoacoustic (PAI) an emerging hybrid biomedical modality based on photoacoustic effects (6-9). In PAI, non-ionizing pulses delivered into Some energy absorbed converted heat, leading transient thermoelastic expansion thus ultrasonic emission. generated waves then detected by transducers form images. It known absorption closely associated physiological properties, hemoglobin concentration oxygen saturation. As result, magnitude emission (i.e., signal), proportional local deposition, reveals physiologically tissue structures. exogenous agents necessary overcome signal tissue. On other hand, these molecules exhibit fast clearance, cross section, non-targeted specificity. Therefore, there need for long blood circulation targeted specificity.Gold (Au) nanoparticles been studied molecular because their bright 700–900 nm toxicity (10). can be tuned emit wavelengths changing sizes, shapes, composition, broad excitation profiles coefficients. coated capped hydrophilic materials additional conjugation peptides, antibodies, nucleic acids, organic compounds vitro vivo studies. Use Au has approved United States Food Drug Administration treatment patients rheumatoid arthritis. X-ray/computed tomography, coherence tomography (PAT) (3). nanocages (AuNCs) biocompatible, toxicity, tunable strong (11). outer edge ~50 inner ~42 nm, wall thickness ~4 nm. Yang et al. (12) performed PAT cerebral cortex rats polyethylene glycol–coated AuNCs (PEG-AuNCs) agent. investigators observed enhanced vasculature cortex. Song (13) demonstrated use PAI probe sentinel lymph nodes rats.Endothelial cells important inflammatory responses (14, 15). Bacterial lipopolysaccharide, virus, inflammation, injury increase tumor necrosis factor α (TNFα), interleukin-1 (IL-1), cytokine chemokine secretion. Emigration leukocytes dependent ability adhere endothelial cell surfaces. Inflammatory mediators cytokines induce secretion vascular expression surface adhesion molecules, intracellular molecule-1 (ICAM-1), (VCAM-1), integrins, selectins. Chemokines chemotactic toward sites inflammation injury. movement through junctions extravascular space highly orchestrated various interactions different (16).VCAM-1 found very levels resting cells, smooth muscle fibroblasts (16-20). VCAM-1 binds late antigen-4 (VLA-4) integrin leukocytes. IL-1 TNFα leads leukocyte activated endothelium. Furthermore, induced oxidized low-density lipoproteins under atherogenic conditions (21). Overexpression atherosclerotic lesions plays role progression vulnerable plaques, may erode rupture. Rouleau (22) developed gold nanoshells glycol (PEG) anti-VCAM-1 antibody (AuNS-PEG-VCAM-1Ab) plaques mice.