Changqiang Wu

Amphiphilic starlike dextran wrapped superparamagnetic iron oxide nanoparticle clsuters as effective magnetic resonance imaging probes

Starlike polymers have been widely used in various fields, such as tissue engineering, imaging, gene and drug delivery because of their unique structures and properties. Dextran has long been used as a temporary plasma substitute because of its excellent biocompatibility. In this study, starlike polysaccharide with multiple dextran arms was designed and developed by attaching dextran to a β-cyclodextrin core through click chemistry. Next, starlike dextran was modified with aliphatic chains and these amphiphilic polymers can self-assemble into nanoscale micelles in water, and their critical micelle concentration values (3.7 × 10(-8) M) are much lower comparing to its linear analogs (1.7 × 10(-7) M), resulting in more stable nanostructures in aqueous environment. These micelles can encapsulate multiple superparamagnetic iron oxide nanoparticles and forming clustering particle nanostructures in water, and the resulting nanocomposites have a high T(2) relaxivity of 436.8 Fe mm(-1) s(-1) under a 1.5T clinical magnetic resonance imaging (MRI) scanner. Further, dual functional probes were developed by loading both superparamagnetic iron oxide nanoparticles and small molecule anticancer drug doxorubicin into polymeric micelles. Multidrug-resistant breast cancer cells MCF-7/Adr treated with these probes can be characterized under MRI.

Superparamagnetic MRI probes for in vivo tracking of dendritic cell migration with a clinical 3 T scanner

Dendritic cell (DC) based vaccines have shown promising results in the immunotherapy of cancers and other diseases. How to track the in vivo fate of DC vaccines will provide important insights to the final therapeutic results. In this study, we chose magnetic resonance imaging (MRI) to track murine DCs migration to the draining lymph node under a clinical 3 T scanner. Different from labeling immature DCs usually reported in literature, this study instead labeled matured DC with superparamagnetic iron oxide (SPIO) nanoparticle based imaging probes. The labeling process did not show negative impacts on cell viability, morphology, and surface biomarker expression. To overcome the imaging challenges brought by the limitations of the scanner, the size of lymph node, and the number of labeled cell, we optimized MRI pulse sequences. As a result, the signal reduction, caused either by gelatin phantoms containing as low as 12 SPIO-laden cells in each voxel or by the homing SPIO-laden DCs within the draining nodes after footpad injection of only 1 × 10(5) cells, can be clearly depicted under a 3 T MR scanner. Overall, the MRI labeling probes offer a low-toxic and high-efficient MR imaging platform for the assessment of DC-based immunotherapies.

Multivalent manganese complex decorated amphiphilic dextran micelles as sensitive MRI probes

T1 contrast agents based on Mn(II) were conjugated on amphiphilic dextran micelles via click chemistry. The obtained paramagnetic nanomicelle contrast agent has a higher T1 relaxivity (13.3 Mn mmol-1 s-1) and better sensitivity than those of free Mn(II) complexes. Studies carried out in vivo suggest that this contrast agent has a better and long-acting vascular enhancement effect at a lower manganese dosage (0.1 Mn mmol kg-1 BW).

Tracking tumor cells in lymphatics in a mice xenograft model by magnetic resonance imaging.

To enrich our understanding of the mechanism of tumor lymphatic metastasis, we developed a model system for tracking metastatic tumor cells in the lymphatic system with cellular magnetic resonance imaging (MRI) in live mice to observe the interaction between tumor cells and the lymphatic system. Nude mice were inoculated subcutaneously with superparamagnetic iron oxide (SPIO)-labeled and unlabeled LOVO cells in the foot pad, groin, or axillary area. Serial 7 T MRI of the tumors and surrounding regions was performed in the following 2 weeks. After imaging, tumor tissues and regional lymph nodes were collected and subjected to immunohistologic analysis. T2/T2*-weighted MRIs showed the primary tumor growth and the draining lymphatic architecture, as well as the SPIO-labeled tumor cells metastasized into the regional lymph node at 8 days. MRIs also revealed information on sentinel lymph node mapping with high-resolution anatomic information. Histologic findings confirmed the in vivo MRI results and revealed lymphangiogenesis, angiogenesis, infiltration of macrophages, and expression of vascular endothelial growth factor C in tumor and draining lymph nodes as well. This technology provides a powerful tool for tracking SPIO-labeled cancer cells in the lymphatics by cellular MRI. There was a close relationship between tumor lymphatic metastasis and lymphangiogenesis.

Ex-vivo biodistribution and micro-PET/CT imaging of 18F-FDG, 18F-FLT, 18F-FMISO, and 18F-AlF-NOTA-PRGD2 in a prostate tumor-bearing nude mouse model.

Objective18F-Fluorodeoxyglucose (18F-FDG), 18F-fluoro-3′-deoxy-3′-L-fluorothymidine (18F-FLT), 18F-fluoromisonidazole (18F-FMISO), and 18F-AlF-NOTA-PRGD2 (18F-RGD) are all commonly used PET tracers for tumor diagnosis based on different mechanisms of tissue uptake. This study compared the ex-vivo biodistribution and PET/computed tomography (CT) imaging studies of these four PET tracers in a xenograft prostate tumor-bearing mouse model. Materials and methodsNude mice were inoculated with 5×106 PC-3 cells in the right armpit. The ex-vivo biodistribution of 18F-FDG, 18F-FLT, 18F-FMISO, and 18F-RGD at 30, 60, 90, and 120 min after injection was compared. Micro-PET/CT images of 18F-FDG, 18F-FLT, and 18F-RGD were acquired at 60 min, whereas 18F-FMISO images were acquired at 90 min after injection. ResultsThe tumors were clearly visualized by micro-PET/CT using all four PET tracers. Ex-vivo biodistribution results showed highest tumor accumulation and tumor-to-muscle ratio of 18F-FDG at each time point, accompanied by physiologically high uptakes in the brain, heart, and intestinal tract. Modest uptake of 18F-FLT and 18F-FMISO in tumors was observed at 60 and 90 min after injection, with less interference from other tissues compared with 18F-FDG. Besides, 18F-RGD also exhibited high tumor specificity; however, relatively low uptake was observed in the tumor. ConclusionOur results demonstrated the potential of 18F-FMISO and 18F-FLT in the diagnosis of xenograft prostate cancer.