MRI and NIR-active, multi-modal and theranostic Composite NanoCarriers (CNCs) have been
developed using a simple one-step process, Flash NanoPrecipitation (FNP). The CNCs have higher MRI T2 contrast
and drug loading than have been reported for carriers produced by more complex assembly processes. In the
controlled precipitation process, 10 nm iron oxide-based nanocrystals (IONCs) were encapsulated into poly(ethylene
glycol) stabilized CNCs to make biocompatible T2 contrast agents. By adjusting the formulation, the CNC size was
tuned between 80 and 360 nm. Holding the CNC size constant at 99 nm ± 3 nm, the particle relaxivity varied linearly
with encapsulated IONC content ranging from 66 to 533 mM-1s-1 for CNCs with 4 to 16 wt% IONCs. By
functionalizing the CNC surface with hydroxyl groups, the CNCs targeted the liver. The CNCs darkened healthy liver
tissue, which enabled the detection of 0.8 mm3 non-small cell lung cancer metastases in vivo. Incorporation of the
hydrophobic NIR dye, PZn3, into CNCs enabled visualization with long wavelength fluorescence at 800 nm as well as
MRI imaging. Both the dye and IONC were encapsulated into the core of the CNCs. In vivo imaging demonstrated the
ability of these particles to act both as MRI and fluorescent imaging agents and to circulate in the blood over 24 hours.
To demonstrate the high drug-loading capabilities of CNCs formed via FNP, a theranostic CNC was created by the
single step, block copolymer-directed assembly of IONCs and itraconazole. The CNC had an ITZ drug loading of 47%.
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