Multicellular layers(MCLs) have previously been used to determine the pharmacokinetics of a variety of different cancer drugs including paclitaxel, doxorubicin, methotrexate, and 5-fluorouracil across a number of cell...Multicellular layers(MCLs) have previously been used to determine the pharmacokinetics of a variety of different cancer drugs including paclitaxel, doxorubicin, methotrexate, and 5-fluorouracil across a number of cell lines. It is not known how nanoparticles(NPs) navigate through the tumor microenvironment once they leave the tumor blood vessel.In this study, we used the MCL model to study the uptake and penetration dynamics of NPs. Gold nanoparticles(GNPs)were used as a model system to map the NP distribution within tissue-like structures. Our results show that NP uptake and transport are dependent on the tumor cell type. MDA-MB-231 tissue showed deeper penetration of GNPs as compared to MCF-7 one. Intracellular and extracellular distributions of NPs were mapped using Cyto Viva imaging. The ability of MCLs to mimic tumor tissue characteristics makes them a useful tool in assessing the efficacy of particle distribution in solid tumors.展开更多
Gold nanoparticles(GNPs) are emerging as a novel tool to improve existing cancer therapeutics. GNPs are being used as radiation dose enhancers in radiation therapy as well as anticancer drugs carriers in chemotherapy....Gold nanoparticles(GNPs) are emerging as a novel tool to improve existing cancer therapeutics. GNPs are being used as radiation dose enhancers in radiation therapy as well as anticancer drugs carriers in chemotherapy. However,the success of GNP-based therapeutics depends on their ability to penetrate tumor tissue. GNPs of 20 and 50 nm diameters were used to elucidate the effects of size on the GNP interaction with tumor cells at monolayer and multilayer level. At monolayer cell level, smaller NPs had a lower uptake compared to larger NPs at monolayer cell level. However, the order was reversed at tissue-like multilayer level. The smaller NPs penetrated better compared to larger NPs in tissue-like materials.Based on our study using tissue-like materials, we can predict that the smaller NPs are better for future therapeutics due to their greater penetration in tumor tissue once leaving the leaky blood vessels. In this study, tissue-like multilayer cellular structures(MLCs) were grown to model the post-vascular tumor environment. The MLCs exhibited a much more extensive extracellular matrix than monolayer cell cultures. The MLC model can be used to optimize the nano–micro interface at tissue level before moving into animal models. This would accelerate the use of NPs in future cancer therapeutics.展开更多
Objective: To optimize scan time and X-ray dose with no loss of image quality for retrospectively gated micro-CT scans of free-breathing rats. Methods: Five free-breathing rats were scanned using a dynamic micro-CT sc...Objective: To optimize scan time and X-ray dose with no loss of image quality for retrospectively gated micro-CT scans of free-breathing rats. Methods: Five free-breathing rats were scanned using a dynamic micro-CT scanner over 10 continuous gantry rotations (50 seconds and entrance dose of 0.28 Gy). The in-phase projection views were selected and reconstructed, representing peak inspiration and end expiration from all 10 rotations and progressively fewer rotations. A least error method was also used to ensure that all angular positions were filled. Image quality and reproducibility for physiological measurements were compared for the two techniques. Results: The least error approach underestimated the lung volume, air content in the lung at peak inspiration, and tidal volume. Other measurements showed no differences between the projection-sorting techniques. Conclusions: Seven gantry rotations (35 seconds and 0.2 Gy dose) proved to be the optimal protocol for both the in-phase images and the least error images.展开更多
文摘Multicellular layers(MCLs) have previously been used to determine the pharmacokinetics of a variety of different cancer drugs including paclitaxel, doxorubicin, methotrexate, and 5-fluorouracil across a number of cell lines. It is not known how nanoparticles(NPs) navigate through the tumor microenvironment once they leave the tumor blood vessel.In this study, we used the MCL model to study the uptake and penetration dynamics of NPs. Gold nanoparticles(GNPs)were used as a model system to map the NP distribution within tissue-like structures. Our results show that NP uptake and transport are dependent on the tumor cell type. MDA-MB-231 tissue showed deeper penetration of GNPs as compared to MCF-7 one. Intracellular and extracellular distributions of NPs were mapped using Cyto Viva imaging. The ability of MCLs to mimic tumor tissue characteristics makes them a useful tool in assessing the efficacy of particle distribution in solid tumors.
基金the Natural Sciences and Engineering Research Council of Canada(NSERC)Canadian Foundation for Innovation(CFI)
文摘Gold nanoparticles(GNPs) are emerging as a novel tool to improve existing cancer therapeutics. GNPs are being used as radiation dose enhancers in radiation therapy as well as anticancer drugs carriers in chemotherapy. However,the success of GNP-based therapeutics depends on their ability to penetrate tumor tissue. GNPs of 20 and 50 nm diameters were used to elucidate the effects of size on the GNP interaction with tumor cells at monolayer and multilayer level. At monolayer cell level, smaller NPs had a lower uptake compared to larger NPs at monolayer cell level. However, the order was reversed at tissue-like multilayer level. The smaller NPs penetrated better compared to larger NPs in tissue-like materials.Based on our study using tissue-like materials, we can predict that the smaller NPs are better for future therapeutics due to their greater penetration in tumor tissue once leaving the leaky blood vessels. In this study, tissue-like multilayer cellular structures(MLCs) were grown to model the post-vascular tumor environment. The MLCs exhibited a much more extensive extracellular matrix than monolayer cell cultures. The MLC model can be used to optimize the nano–micro interface at tissue level before moving into animal models. This would accelerate the use of NPs in future cancer therapeutics.
文摘Objective: To optimize scan time and X-ray dose with no loss of image quality for retrospectively gated micro-CT scans of free-breathing rats. Methods: Five free-breathing rats were scanned using a dynamic micro-CT scanner over 10 continuous gantry rotations (50 seconds and entrance dose of 0.28 Gy). The in-phase projection views were selected and reconstructed, representing peak inspiration and end expiration from all 10 rotations and progressively fewer rotations. A least error method was also used to ensure that all angular positions were filled. Image quality and reproducibility for physiological measurements were compared for the two techniques. Results: The least error approach underestimated the lung volume, air content in the lung at peak inspiration, and tidal volume. Other measurements showed no differences between the projection-sorting techniques. Conclusions: Seven gantry rotations (35 seconds and 0.2 Gy dose) proved to be the optimal protocol for both the in-phase images and the least error images.