Size-tunable MRI-visible nitroxide-based magnetic mixed micelles: preparation, stability, and theranostic application.

Metal-free magnetic mixed micelles (mean diameter: 16 nm) composed of biocompatible surfactant Tween 80 and hydrophobic pyrrolidine-<i>N</i>-oxyl radical were prepared by mixing them in phosphate-buffered saline (PBS). The magnetic mixed micelles were characterized by dynamic light scattering (DLS) and small angle neutron scattering (SANS) measurements. The stability of the micelles is found to depend on the length of alkyl side chain in the nitroxide compounds and degree of unsaturation in the hydrophobic chain in the surfactant. The size of the mixed micelle can be tuned by changing the molar ratio of Tween 80 and nitroxyl radical. In view of theranostic application of the micelle, the cytotoxicity and stability in a physiological environment was investigated; the mixed micelle exhibited no cytotoxicity, high colloidal stability and high resistance towards reduction by large excess ascorbic acid. The in vitro and in vivo magnetic resonance imaging (MRI) revealed sufficient contrast enhancement in the proton longitudinal relaxation time (<i>T</i><sub>1</sub>) weighted images. In addition, hydrophobic fluorophores and an anticancer drug are stably encapsulated in the mixed micelles and showed fluorescence (FL) upon reduction by ascorbic acid and cytotoxicity to cancer cells, respectively. For example, the paclitaxel-loaded mixed micelles efficiently suppressed cancer cell growth. Furthermore, they were found to give higher MRI contrast (higher <i>r</i><sub>1</sub> value) in vitro than the micelles without paclitaxel. The magnetic mixed micelles presented here are promising theranostic agents in nanomedicine due to their high biocompatibility and high resistivity towards reduction as well as functions as drug carrier in therapy and MR or FL imaging probe in diagnosis.