MRI and NIR-active, multi-modal Composite NanoCarriers (CNCs) are prepared using a simple, one-step process, Flash NanoPrecipitation (FNP). The FNP process allows for the independent control of the hydrodynamic diameter, co-core excipient and NIR dye loading, and iron oxide-based nanocrystal (IONC) content of the CNCs. In the controlled precipitation process, 10 nm IONCs are encapsulated into poly(ethylene glycol) stabilized CNCs to make biocompatible T2 contrast agents. By adjusting the formulation, CNC size is tuned between 80 and 360 nm. Holding the CNC size constant at an intensity weighted average diameter of 99 ± 3 nm (PDI width 28 nm), the particle relaxivity varies linearly with encapsulated IONC content ranging from 66 to 533 mM-1s-1 for CNCs formulated with 4 to 16 wt% IONC. To demonstrate the use of CNCs as in vivo MRI contrast agents, CNCs are surface functionalized with liver targeting hydroxyl groups. The CNCs enable the detection of 0.8 mm3 non-small cell lung cancer metastases in mice livers via MRI. Incorporating the hydrophobic, NIR dye PZn3 into CNCs enables complementary visualization with long-wavelength fluorescence at 800 nm. In vivo imaging demonstrates the ability of CNCs to act both as MRI and fluorescent imaging agents.
A statistical design of experiments was used to study the effect of reaction temperature and time on the synthesis of cobalt ferrite nanoparticles by the thermodecomposition method. A 24–2 factorial experimental design with two central points was used in which the control variables were the time and temperature of the nucleation and growth stages. Transmission electron microscopy, X-ray diffraction, inductively coupled plasma optical emission spectroscopy, and magnetic measurements were used for particle characterization. Cobalt-substituted ferrite (CoxFe3−xO4) nanoparticles with diameters between 9 nm and 13 nm were obtained by varying the nucleation temperature between 150°C and 250°C, the growth temperature between 300°C and 330°C, and the time in each stage between 60 min and 120 min. Statistical analysis showed that only the temperatures had an influence on the final particle size. The analysis of variance indicates that increase in the nucleation temperature resulted in decreased particle size, whereas the increase in temperature in the growth stage resulted in an increase in particle size. Additionally, statistical analysis showed that the growth temperature had an effect on Fe/Co ratio. An increase in the growth temperature produces a decrease in the Fe/Co ratio. Finally, a statistically significant correlation was found between particle diameter and saturation magnetization at 5 K and 300 K. No correlation was found between diameter and other magnetic properties.
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