The development of new nanoparticles as next-generation diagnostic and therapeutic ("theranostic") drug platforms is an active area of both chemistry and cancer research. Although numerous gadolinium (Gd) containing metallofullerenes as diagnostic magnetic resonance imaging (MRI) contrast agents have been reported, the metallofullerene cage surface, in most cases, consists of negatively charged carboxyl or hydroxyl groups that limit attractive forces with the cellular surface. It has been reported that nanoparticles with a positive charge will bind more efficiently to negatively charged phospholipid bilayer cellular surfaces, and will more readily undergo endocytosis. In this paper, we report the preparation of a new functionalized trimetallic nitride template endohedral metallofullerene (TNT EMF), Gd3N@C80(OH)x(NH2)y, with a cage surface bearing positively charged amino groups (-NH3(+)) and directly compare it with a similar carboxyl and hydroxyl functionalized derivative. This new nanoparticle was characterized by X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), and infrared spectroscopy. It exhibits excellent (1)H MR relaxivity. Previous studies have clearly demonstrated that the cytokine interleukin-13 (IL-13) effectively targets glioblastoma multiforme (GBM) cells, which are known to overexpress IL-13Rα2. We also report that this amino-coated Gd-nanoplatform, when subsequently conjugated with interleukin-13 peptide IL-13-Gd3N@C80(OH)x(NH2)y, exhibits enhanced targeting of U-251 GBM cell lines and can be effectively delivered intravenously in an orthotopic GBM mouse model.
Appendicitis remains the most common surgical pathology responsible for right lower quadrant (RLQ) abdominal pain presenting to emergency departments in the United States, where the incidence continues to increase. Appropriate imaging in the diagnosis of appendicitis has resulted in decreased negative appendectomy rate from as high as 25% to approximately 1% to 3%. Contrast-enhanced CT remains the primary and most appropriate imaging modality to evaluate this patient population. MRI is approaching CT in sensitivity and specificity as this technology becomes more widely available and utilization increases. Unenhanced MRI and ultrasound remain the diagnostic procedures of choice in the pregnant patient. MRI and ultrasound continue to perform best in the hands of experts.
Flow-dependent vasodilation in isolated perfused segments of bovine carotid arteries was maximal when the intraluminal pressures were low and when the vessels were precontracted with norepinephrine. Flow-dependent vasodilation was inhibited by methylene blue and was associated with increases in the phosphorylation of HSP20, suggesting that the vasodilation was mediated by endothelial production of nitric oxide.
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