Background: Understanding how nanomaterials are distributed in the body after exposure is important for assessing whether they are safe. In this study, we investigated the behavior and accumulation of nanoscaled and submicron-scaled zinc oxide (ZnO) particles in the body using optical imaging following oral exposure. Methods: To trace these nanoparticles in the body, ZnO nanoparticles were conjugated with a monoreactive hydroxysuccinimide ester of Cy5.5 (Cy5.5-NHS), and the conjugation-stabilizing effect of Cy5.5 on the nanoparticles was evaluated in simulated gastric fluid (pH 1.2) for 7 hours. To compare the distribution of Cy5.5-NHS and Cy5.5-conjugated ZnO nanoparticles, Cy5.5-NHS 0.5 mg/kg and Cy5.5-conjugated ZnO nanoparticles 250 mg/kg were administered orally to healthy rats. We collected blood from the rats at predesignated time points for 7 hours after administration, and optical imaging studies were performed at 1, 2, 3, 5, and 7 hours after dosing. To investigate the extent of nanoparticle accumulation in the organs and tissues, the mice were sacrificed at 23 hours after administration, and the organs were removed and imaged. Results: Cy5.5-conjugated ZnO nanoparticles were stable in simulated gastric fluid for 7 hours. The signal intensity of Cy5.5-NHS in blood was highest 3 hours after oral administration, and Cy5.5-conjugated ZnO nanoparticles showed the highest signal intensity in blood 5–7 hours after administration. In vivo optical images indicated that Cy5.5-NHS showed optical signals in the lung, liver, and gastrointestinal tract after oral administration, whereas Cy5.5-conjugated ZnO nanoparticles were seen only in the gastrointestinal tract. Seven hours following administration, biodistribution studies demonstrated that Cy5.5-NHS accumulated in the lung and liver, and Cy5.5-conjugated ZnO nanoparticles resulted in a strong signal in the kidney and liver. Different-sized ZnO nanoparticles showed dissimilar patterns of biodistribution in ex vivo optical images. Conclusion: ZnO nanoparticles are absorbed into the tissues following oral exposure and their behavior can be monitored and evaluated using optical imaging.
We designed gold nanoparticles (AuNPs) capped with iodine and polyethylene glycol (PEG) to provide effective enhancement for X‐ray CT imaging. The methoxy PEG‐iodine‐capped AuNPs were prepared through the chemisorption of iodine and substitution of methoxy PEG‐SH onto the surface of gold nanoparticles, and severe aggregation in TEM was not observed. The binding energies of Au 4f7/2 and I 3d5/2 of the methoxy PEG‐iodine‐capped AuNPs were obtained as 84.1 eV and 619.3 eV, respectively. The binding energy shift of methoxy PEG‐iodine‐capped AuNPs would be resulted from the chemisorption between gold nanoparticles and iodine atoms. The methoxy PEG‐iodine‐capped AuNPs have higher enhancement compared to PEG‐capped gold nanoparicles in the same amount of gold in vitro. After postinjection of methoxy PEG‐iodine‐capped AuNPs into the mice, dramatic contrast enhancement at the heart, aorta, liver, and kidney was observed, this was maintained up to 5 days, and there was no evidence of apparent toxicity. In conclusion, methoxy PEG‐iodine‐capped AuNPs might be a good candidate as a CT contrast agent for blood pool imaging, and this will also contribute to the prolongation of a blood circulation time for X‐ray CT imaging.
27 May 2010 in European Journal of Nuclear Medicine and Molecular Imaging
The aim of this study was to investigate the effect of gluconic acid (GA) conjugation on the biodistribution of cysteamine-capped quantum dots (amino-QDots) in vivo. Cadmium selenide/zinc sulfide (CdSe/ZnS) was capped with cysteamine through a thiol exchange method, and different amounts of GA were conjugated to the amine groups of cysteamine via the formation of an amide bond. The emission maxima of the synthesized QDots, the amino-QDots and the GA-conjugated amine-QDots (GA-QDots) were located at 720, 600 and 610 nm, respectively. In the cell viability studies, the GA-QDots showed very low toxicity against CHO cells as compared to the cytotoxicity of the amino-QDots. The QDots were next intravenously injected into normal mice and then we performed ex vivo optical imaging. The majority of the amino-QDots were accumulated in the lung. In contrast, the GA-QDots were cleared out of the body through the kidney. Therefore, we expect that the conjugation of GA onto the amino-QDots can create opportunities for using amino-QDots for in vivo imaging.