Here we report the synthesis of hybrid hollow chitosan-silica nanospheres (CS-Silica NPs) with chitosan-polyacrylic acid (CS-PAA) nanoparticles as the template and doxorubicin (DOX) delivery based on CS-Silica NPs. The morphology and the microstructure of CS-Silica NPs were characterized by field emission scanning electron microscopy (FESEM) and X-ray photoelectron spectroscopy (XPS). The confocal laser scanning microscopy (CLSM) and flow cytometry experiments showed that the cellular uptake of the DOX-loaded CS-Silica NPs was time dependent. In addition, cellular internalization and intracellular distribution of DOX-loaded CS-Silica NPs indicated that the DOX was mainly distributed in the cell nucleus while the carriers were primarily located in the cytoplasm. In vivo antitumor response indicated that the DOX loaded CS-Silica hybrid hollow nanospheres exhibited superior antitumor effect over the free drug in vivo, which might be ascribable to the enhanced cellular uptake efficiency and the effective delivery of drug to the cell nucleus.
Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/ 18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials.
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