Dysregulated host inflammatory response causes many diseases, including cardiovascular and neurodegenerative diseases, cancer, and sepsis. Sensitive detection of the site of inflammation will, therefore, produce a wide-ranging impact on disease diagnosis and treatment. We hypothesized that nanoprobes designed to mimic the molecular interactions occurring between inflamed leukocytes and endothelium may possess selectivity toward diverse host inflammatory responses. To incorporate inflammation-sensitive molecular interactions, superparamagnetic iron oxide nanoparticles were conjugated with integrin lymphocyte function-associated antigen (LFA)-1 I domain, engineered to mimic activated leukocytes in physiology. Whole body optical and magnetic resonance imaging in vivo revealed that leukocyte-mimetic nanoparticles localized preferentially to the vasculature within and in the invasive front of the tumor, as well as to the site of acute inflammation. This study explored in vivo detection of tumor-associated vasculature with systemically injected inflammation-specific nanoparticles, presenting a possibility of tumor detection by inflamed tumor microenvironment.
The ability to use a systemically injected agent to image tumor is influenced by tumor characteristics such as permeability and vascularity, and the size, shape, and affinity of the imaging agent. In this study, six different imaging biomolecules, with or without specificity to tumor, were examined for tumor uptake and internalization at the whole body, ex-vivo tissue, and cellular levels: antibodies, antibody fragments (Fab), serum albumin, and streptavidin. The time of peak tumor uptake was dependent solely on the size of molecules, suggesting that molecular size is the major factor that influences tumor uptake by its effect on systemic clearance and diffusion into tumor. Affinity to tumor antigen failed to augment tumor uptake of Fab above non-specific accumulation, which suggests that Fab fragments of typical monoclonal antibodies may fall below an affinity threshold for use as molecular imaging agents. Despite abundant localization into the tumor, albumin and streptavidin were not found on cell surface or inside cells. By comparing biomolecules differing in size and affinity, our study highlights that while pharmacokinetics are a dominant factor in tumor uptake for biomolecules, affinity to tumor antigen is required for tumor binding and internalization.
The synthesis of ZnO comprising different ratios of zinc acetate (ZA) and zinc nitrate (ZN) from the respective zinc precursor solutions was successfully completed via a simple precipitation method. Zinc oxide powders with different mole ratios of ZA/ZN were produced—80/1, 40/1, and 20/1. The crystallinity, microstructure, and optical properties of all produced ZnO powders were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), and UV-Vis-NIR spectrophotometry. The average agglomerated particle sizes of ZnO-80/1, ZnO-40/1, and ZnO-20/1 were measured at 655, 640, and 620 nm, respectively, using dynamic light scattering (DLS). The optical properties of ZnO were significantly affected by the extreme ratio differences in the zinc precursors. ZnO-80/1 was found to have a unique coral-sheet structure morphology, which resulted in its superior ability to reflect near-infrared (NIR) radiation compared to ZnO-40/1 and ZnO-20/1. The NIR-shielding performances of ZnO were assessed using a thermal insulation test, where coating with ZnO-80/1 could lower the inner temperature by 5.2 °C compared with the neat glass substrate. Due to the synergistic effects on morphology, ZnO-80/1 exhibited the property of enhanced NIR shielding in curtailing the internal building temperature, which allows for its utilization as an NIR-reflective pigment coating in the construction of building envelopes.
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