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Improving target versus off-target ratio in nanomedicine remains a major challenge for increasing drug bioavailability and reducing toxicity. Active targeting using ligands on nanoparticle surfaces is a key approach but has limited clinical success. A potential issue is the integration of targeting ligands also changes the physicochemical properties of nanoparticles (passive targeting). Direct studies to understand the mechanisms of active targeting and off-targeting in vivo are limited by the lack of suitable tools. Here, the biodistribution of a representative active targeting liposome is analyzed, modified with an apolipoprotein E (ApoE) peptide that binds to the low-density lipoprotein receptor (LDLR), using zebrafish embryos. The ApoE liposomes demonstrated the expected liver targeting effect but also accumulated in the kidney glomerulus. The ldlra−/- zebrafish is developed to explore the LDLR-specificity of ApoE liposomes. Interestingly, liver targeting depends on the LDLR-specific interaction, while glomerular accumulation is independent of LDLR and peptide sequence. It is found that cationic charges of peptides and the size of liposomes govern glomerular targeting. Increasing the size of ApoE liposomes can avoid this off-targeting. Taken together, the study shows the potential of the zebrafish embryo model for understanding active and passive targeting mechanisms, that can be used to optimize the design of nanoparticles.  相似文献   
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Clean Technologies and Environmental Policy - Fluidized bed bioreactors are widely used in wastewater treatment applications. Such reactors employ gel beads or hard particles covered with a biofilm...  相似文献   
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Annual anomalies of Lambertian equivalent reflectivity (LER) retrieved from the total ozone mapping spectrometer spanning the period November 1978–November 2005 were studied in the Southern Hemisphere, in a region bounded by 0° S and 60° S, and their trends were estimated. With the exception of few regions where the variable may represent the contribution of both cloudiness and snow, trends in LER anomalies provided an evolution of total cloudiness. On average, the study region experienced a net increase in LER values of 0.78 reflectivity units (RU) decade?1; if only significant trend values are considered this figure increased to 1.18 RU decade?1. The region that showed the largest upward trend, up to 4 RU decade?1, was located over the eastern Pacific, off the coasts of Chile and Peru, where the presence of marine stratocumulus is frequent. Despite the overall positive trend there were regions that yielded a negative one, most notably the tropical latitudes of South America and Africa. The yearly zonal means also showed a positive trend at all latitudes, but significance occurred beyond 20° S only. Correlation maps between LER anomalies and five different circulation indices were also introduced. The indices with the highest and lowest number of significant correlation values were the Madden–Julian oscillation at 70° E and the quasi-biennial Oscillation, respectively.  相似文献   
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