At 50 and 100
mg polysorbate 80, however, MNCs fabricated from MMNPs and HMNPs showed no noticeable distinction in r2 values. The difference of oleic acid content in these two PMNPs is insufficient to differentiate the size and magnetic content of MNCs when high concentrations of polysorbate 80 are employed in the reaction. At excess polysorbate 80 concentrations, polysorbate 80 stabilized the MNCs to form quite small ones. The MNC r2 value variations observed when using a constant amount of polysorbate 80 were derived by primary-ligand modulation. Additionally, the increased r2 values in concert with decreased polysorbate 80 concentrations in the reaction were caused by MNC size increases due to the effect of secondary-ligand Adriamycin clinical trial modulation [23]. Thus, these results demonstrate that modulation of learn more both
primary and secondary ligands is crucial for engineering MNCs to provide maximally enhanced MRI sensitivity. The r2 values of MNCs created from LMNPs using low amount of polysorbate 80 (10 and 25 mg) were not measurable because unstable MNCs were aggregated under an external magnetic field. Detailed MNC r2 values are presented in Additional file 1: Table S3. Figure 3c shows photographs of MNCs dispersed in water and their T2-weighted solution MRIs. MNCs prepared from MMNPs and HMNPs were well dispersed in water without sedimentation, whereas LMNPs showed aggregation with larger cluster size that gradually settled over time. This indicates that insufficient polysorbate 80 concentrations were Staurosporine cost employed to form stable nanoclusters (Additional file 1: Figure S5). In addition, T2-weighted solution MRIs of MNCs obtained at the same iron concentration (0.74 Fe mM) showed darker images with decreased amount of polysorbate 80. Importantly, MNCs
fabricated from LMNPs PIK-5 showed the strongest darkening effect. From these results, in our system, we determined that MNCs fabricated from LMNPs using 50 mg polysorbate 80 exhibited good solubility and provided the greatest enhancement of MRI sensitivity. To investigate the efficiency of the engineered MNCs prepared by double-ligand modulation, we defined another form of relaxivity (r2(S)) that referred the r2 enhancement property based on size increase of MNCs. The r2 enhancement for each PMNP (107.8 ~ 68.5 s−1 mM−1 for LMNPs, 102.7 ~ 19.2 s−1 mM−1 for MMNPs, 44.3 ~ 19.3 s−1 mM−1 for HMNPs) were divided by size increase (59.9 ~ 42.6 nm for LMNPs, 65.1 ~ 15.8 nm for MMNPs, 66.6 ~ 17.1 nm for HMNPs). The r2(S) values thus obtained were 2.3, 1.7, and 0.5 s−1 mM−1 nm−1 for LMNPs, MMNPs, and HMNPs, respectively (Figure 4). The positive value of r2(S) indicated that MNC r2 enhancement was related to MNC size increase in association with using decreasing polysorbate 80 concentrations as the secondary-ligand modulation. However, the difference in r2(S) among LMNPs, MMNPs, and HMNPs meant that the efficiency of the r2 enhancement through the engineering of MNCs depended on the primary-ligand modulation.