Facile preparation and characterization of robust metal-free nitroxide-based magnetic mixed micelles as MRI-visible drug delivery carrier

Title : Facile preparation and characterization of robust metal-free nitroxide-based magnetic mixed micelles as MRI-visible drug delivery carrier

Abstract:

We reported that chiral all-organic rod-like liquid crystalline (LC) compounds with a five-membered cyclic nitroxide unit in the central core position exhibited the spin glass-like inhomogeneous ferromagnetic interactions in the LC phases at high temperatures under low magnetic fields.^[1] Such a unique magnetic phenomenon was referred to as ‘positive magneto-LC effect’.
       With a view to extending the positive magneto-LC effect to other organic radical soft materials, we have prepared robust metal-free magnetic mixed micelles (mean particle sizes: 17 nm) composed of the biocompatible non-ionic PEG-based surfactants and the hydrophobic low-molecular-weight 2,2,5-trimethyl-5-(4-alkoxy)phenylpyrrolidine-N-oxyl radicals in PBS.^[2] The spherical structure of the magnetic mixed micelles has been characterized by electron paramagnetic resonance (EPR) spectroscopy, and dynamic light scattering (DLS) and small angle neutron scattering (SANS) measurements. The mixed micelles showed high colloidal stability, low cytotoxicity, enough reduction resistance to excess ascorbic acid, and sufficient contrast enhancement in the proton longitudinal relaxation time (T₁)-weighted MR images in PBS in vitro and in vivo.
         Furthermore, additional hydrophobic anticancer drugs such as paclitaxel could be encapsulated inside the mixed micelles, and the resulting drug-loaded mixed micelles were efficiently incorporated into HeLa cells to suppress the cell growth. We expect that such drug-loaded mixed micelles can be used as a theranostic nanomedicine for MRI-visible targeted drug delivery system.
Audience take away: 
• This work presents (1) the facile preparation of the first metal-free magnetic mixed micelles (mean particle size < 20 nm) which can be used as MRI-visible targeted drug delivery carriers in vivo and (2) the characterization of the spherical micelle structure.
• The audience can easily prepare the same mixed micelles according to our prescription without failure and use them as robust DDS carriers for their own purpose.
• We already have had a joint-research with medical doctors, because they evaluate the mixed micelles as excellent hydrophobic anti-cancer drugs delivery carrier in vivo.
• The chemical modification on the hydrophilic surface of mixed micelles is feasible, e.g. attachment of peptides.

Biography:

Dr. Tamura received his PhD degree in 1980 at the Graduate School of Science, Kyoto University, Japan. After three-years postdoctoral fellowship supervised by Dr. L. S. Hegedus at Colorado State University and Dr. M. F. Semmelhack at Princeton University in USA, he obtained the positions of an Assistant Professor at the National Defense Academy in 1983, an Associate Professor at Ehime University in 1988, at Hokkaido University in 1995 and at Kyoto University in 1997, and a Professor at Kyoto University in 2002. He was retired from Kyoto University in 2018. He has published more than 200 research articles.